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Novel BRAF-inhibitor cream ameliorates rash from EGFR inhibitors
The results come from a first-in-human, phase 1 clinical trial conducted in 10 patients with metastatic colorectal cancer who were receiving treatment with either cetuximab or panitumumab and who developed a grade 1 or grade 2 rash while on treatment.
All were treated with the novel topical cream, dubbed LUTO14 (under development by Lutris Pharma).
For 6 of the 10 patients, the acneiform rash improved, according to investigator Mario Lacouture, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues.
The study was published online in Cancer Discovery.
“Based on preclinical modeling and early clinical trial testing, we conclude that improving a topmost adverse event of EGFR inhibitor therapy with topical LUT014 could allow [maintenance of] quality of life and dose intensity, thereby maximizing the antitumor effects [from EGFR inhibitor therapy] while locally inhibiting dose-limiting skin toxicities,” the investigators wrote.
The cream was well tolerated, and no dose-limiting toxicity or maximum tolerated dose was observed, although the cream did appear to be more effective at lower doses.
Rash is a common side effect of EGFR inhibitors. Previous studies have reported that 75%-90% of patients experience “some form of papulopustular, acneiform rash, which frequently leads to ... suboptimal anticancer treatment due to treatment interruptions, dose reductions, or permanent discontinuation of EGFR inhibitor therapy,” the investigators noted.
Paradoxical mechanism of action
How the novel cream containing a BRAF inhibitor helps ameliorate EGFR inhibitor–induced skin toxicity is complicated, but at a cellular level, the mechanism seems somewhat paradoxical, the team commented.
Skin toxicity experienced in the setting of EGFR inhibitor therapy is induced by inhibition of the mitogen-activated protein kinase (MAPK) pathway. Downstream inhibition of the MAPK pathway results in, among other effects, inflammatory changes in epithelial cells that mediate the acneiform rash on the skin.
In contrast, “BRAF inhibitors given systemically have an opposite effect on epithelial cells, resulting in paradoxical activation of the MAPK pathway,” the authors explained. They hypothesized that topical administration of BRAF inhibitors similarly activates the MAPK pathway in epithelial cells, although it was important to develop a specific BRAF inhibitor that would optimally induce paradoxical MAPK activation. That they managed to do so was shown when they evaluated LUT014 in cell culture systems.
The next phase of the study is designed to include approximately 120 patients recruited from centers in the United States and Israel. Interim results are expected by the end of 2021.
The study was funded by Lutris Pharma, the company developing LUT014.
A version of this article first appeared on Medscape.com.
The results come from a first-in-human, phase 1 clinical trial conducted in 10 patients with metastatic colorectal cancer who were receiving treatment with either cetuximab or panitumumab and who developed a grade 1 or grade 2 rash while on treatment.
All were treated with the novel topical cream, dubbed LUTO14 (under development by Lutris Pharma).
For 6 of the 10 patients, the acneiform rash improved, according to investigator Mario Lacouture, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues.
The study was published online in Cancer Discovery.
“Based on preclinical modeling and early clinical trial testing, we conclude that improving a topmost adverse event of EGFR inhibitor therapy with topical LUT014 could allow [maintenance of] quality of life and dose intensity, thereby maximizing the antitumor effects [from EGFR inhibitor therapy] while locally inhibiting dose-limiting skin toxicities,” the investigators wrote.
The cream was well tolerated, and no dose-limiting toxicity or maximum tolerated dose was observed, although the cream did appear to be more effective at lower doses.
Rash is a common side effect of EGFR inhibitors. Previous studies have reported that 75%-90% of patients experience “some form of papulopustular, acneiform rash, which frequently leads to ... suboptimal anticancer treatment due to treatment interruptions, dose reductions, or permanent discontinuation of EGFR inhibitor therapy,” the investigators noted.
Paradoxical mechanism of action
How the novel cream containing a BRAF inhibitor helps ameliorate EGFR inhibitor–induced skin toxicity is complicated, but at a cellular level, the mechanism seems somewhat paradoxical, the team commented.
Skin toxicity experienced in the setting of EGFR inhibitor therapy is induced by inhibition of the mitogen-activated protein kinase (MAPK) pathway. Downstream inhibition of the MAPK pathway results in, among other effects, inflammatory changes in epithelial cells that mediate the acneiform rash on the skin.
In contrast, “BRAF inhibitors given systemically have an opposite effect on epithelial cells, resulting in paradoxical activation of the MAPK pathway,” the authors explained. They hypothesized that topical administration of BRAF inhibitors similarly activates the MAPK pathway in epithelial cells, although it was important to develop a specific BRAF inhibitor that would optimally induce paradoxical MAPK activation. That they managed to do so was shown when they evaluated LUT014 in cell culture systems.
The next phase of the study is designed to include approximately 120 patients recruited from centers in the United States and Israel. Interim results are expected by the end of 2021.
The study was funded by Lutris Pharma, the company developing LUT014.
A version of this article first appeared on Medscape.com.
The results come from a first-in-human, phase 1 clinical trial conducted in 10 patients with metastatic colorectal cancer who were receiving treatment with either cetuximab or panitumumab and who developed a grade 1 or grade 2 rash while on treatment.
All were treated with the novel topical cream, dubbed LUTO14 (under development by Lutris Pharma).
For 6 of the 10 patients, the acneiform rash improved, according to investigator Mario Lacouture, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues.
The study was published online in Cancer Discovery.
“Based on preclinical modeling and early clinical trial testing, we conclude that improving a topmost adverse event of EGFR inhibitor therapy with topical LUT014 could allow [maintenance of] quality of life and dose intensity, thereby maximizing the antitumor effects [from EGFR inhibitor therapy] while locally inhibiting dose-limiting skin toxicities,” the investigators wrote.
The cream was well tolerated, and no dose-limiting toxicity or maximum tolerated dose was observed, although the cream did appear to be more effective at lower doses.
Rash is a common side effect of EGFR inhibitors. Previous studies have reported that 75%-90% of patients experience “some form of papulopustular, acneiform rash, which frequently leads to ... suboptimal anticancer treatment due to treatment interruptions, dose reductions, or permanent discontinuation of EGFR inhibitor therapy,” the investigators noted.
Paradoxical mechanism of action
How the novel cream containing a BRAF inhibitor helps ameliorate EGFR inhibitor–induced skin toxicity is complicated, but at a cellular level, the mechanism seems somewhat paradoxical, the team commented.
Skin toxicity experienced in the setting of EGFR inhibitor therapy is induced by inhibition of the mitogen-activated protein kinase (MAPK) pathway. Downstream inhibition of the MAPK pathway results in, among other effects, inflammatory changes in epithelial cells that mediate the acneiform rash on the skin.
In contrast, “BRAF inhibitors given systemically have an opposite effect on epithelial cells, resulting in paradoxical activation of the MAPK pathway,” the authors explained. They hypothesized that topical administration of BRAF inhibitors similarly activates the MAPK pathway in epithelial cells, although it was important to develop a specific BRAF inhibitor that would optimally induce paradoxical MAPK activation. That they managed to do so was shown when they evaluated LUT014 in cell culture systems.
The next phase of the study is designed to include approximately 120 patients recruited from centers in the United States and Israel. Interim results are expected by the end of 2021.
The study was funded by Lutris Pharma, the company developing LUT014.
A version of this article first appeared on Medscape.com.
New data dim hopes for ‘triumph of drug discovery’
Hopes for a new category of agents recently hailed as “a triumph of drug discovery” have been dimmed somewhat by new data showing many types of acquired resistance.
KRAS is one of the most frequently mutated oncogenes in human cancer and has long been thought “undruggable” – but novel drugs acting specifically on the KRAS G12C mutation have shown promise in clinical trials.
Early results with the experimental KRAS inhibitors sotorasib and adagrasib were deemed promising, but new data presented at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract LB002) have splashed cold water on that enthusiasm.
The efficacy of these new drugs looks to be threatened by the development of resistance caused by a wide range of genomic and histologic mechanisms.
Mark M. Awad, MD, PhD, from the Dana-Farber Cancer Institute in Boston, reported data from 30 patients with non–small cell lung cancer (NSCLC) or colorectal cancer (CRC) bearing the KRAS G12C mutation who had disease progression while being treated with adagrasib in clinical trials. Investigators found multiple on-target KRAS alterations and off-target bypass mechanisms of acquired resistance to adagrasib in these patients.
“Diverse mechanisms confer resistance to the KRAS G12C inhibitors, including secondary KRAS mutations, MAP [mitogen-activated protein] kinase pathway alterations, acquired genomic rearrangements, and histologic transformation,” Dr. Awad said in a mini-symposium presentation.
“Several cases displayed multiple resistance mechanisms, and novel combinatorial strategies will be necessary to delay or overcome resistance in KRAS G12C-mutant cancers,” he said.
Inactivating KRAS
The KRAS G12C mutation is a glycine-to-cysteine substitution that results in the oncogene being switched on in its active form.
But the mutation has been considered too tough to target because of the KRAS gene’s strong binding affinity for guanosine triphosphate, an essential building block of RNA synthesis, and by a lack of accessible drug-binding sites.
Sotorasib and adagrasib are small-molecule, specific, and irreversible inhibitors of KRAS that interact with a “pocket” on the gene’s surface that is present only in an inactive conformation of KRAS. The drugs inhibit oncogenic signaling and tumorigenesis by preventing cycling of the oncogene into its active form.
Multiple mutations, histologic transformations
Dr. Awad and colleagues studied biopsy samples and circulating tumor DNA (ctDNA) from 30 patients both at baseline and after administration of adagrasib monotherapy. The patients all had initial responses to the drug but then experienced disease progression.
The investigators used mutagenesis screens to identify mechanisms of resistance to KRAS G12C inhibitors.
The 30 patients included 23 with NSCLC and 7 with CRC. Eighteen had unknown mechanisms of resistance, and putative resistance mechanisms were identified in the other 12 patients. Of this latter group, seven appeared to have single resistance mechanisms, and five had multiple mechanisms of resistance.
One patient with NSCLC who had radiographic evidence of response followed by progression was found to have had a novel KRAS Y96C mutation, and three had novel KRAS mutations in other gene regions, with multiple concurrent alterations in genes implicated in other forms of cancer, such as PTEN, BRAF, and MAP2K1.
The investigators also identified amplifications of the KRAS G12C allele, and MET.
In two patients, NSCLC underwent histologic transformation from adenocarcinoma at baseline to squamous cell carcinoma at the time of acquired resistance to the drug. No genomic resistance mechanisms were detected in either of these patients, Dr. Awad said.
“In several cases, we see multiple mechanisms or co-occurring alterations in each individual patient, with the suggestion that perhaps the multiple mutations or resistance mechanism may be more common in the colorectal population, particularly with acquired gene fusions, than in the lung cancer population, although larger datasets will be needed to confirm this observation,” he said.
Does duration of response matter?
In the question-and-answer session following his presentation, Dr. Awad was asked about clinical responses in the patients who developed resistance.
“In this initial reporting of resistance mechanisms we did not overlay or report out the clinical outcomes, including the durations of response or the time to disease progression, in part because this is an ongoing clinical trial, and those data will be reported in full at a later time,” Dr. Awad replied. “But I think it will be really important to identify whether patients are more likely to develop resistance earlier versus later or have different resistance mechanisms.”
Dr. Awad commented further that the resistance to adagrasib appeared to be acquired. “These resistance mutations were not detected to the level of detection at the baseline samples. So presumably they may be present at some low levels at the time of initial diagnosis, or they emerge over the course of therapy,” he said.
“Many of the resistance mechanisms appear to be more subclonal, occurring at an allele fraction lower than the original KRAS G12C mutation, which we know is the clonal event in the entire population of the cancer, and I think when we’re seeing these multiple resistance mechanisms emerging, they are potentially each representing different subclones that can develop simultaneously,” he added.
Adagrasib trials are supported by Mirati Therapeutics. Dr. Awad disclosed consulting for Mirati and others, and institutional research support from several different companies.
A version of this article first appeared on Medscape.com.
Hopes for a new category of agents recently hailed as “a triumph of drug discovery” have been dimmed somewhat by new data showing many types of acquired resistance.
KRAS is one of the most frequently mutated oncogenes in human cancer and has long been thought “undruggable” – but novel drugs acting specifically on the KRAS G12C mutation have shown promise in clinical trials.
Early results with the experimental KRAS inhibitors sotorasib and adagrasib were deemed promising, but new data presented at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract LB002) have splashed cold water on that enthusiasm.
The efficacy of these new drugs looks to be threatened by the development of resistance caused by a wide range of genomic and histologic mechanisms.
Mark M. Awad, MD, PhD, from the Dana-Farber Cancer Institute in Boston, reported data from 30 patients with non–small cell lung cancer (NSCLC) or colorectal cancer (CRC) bearing the KRAS G12C mutation who had disease progression while being treated with adagrasib in clinical trials. Investigators found multiple on-target KRAS alterations and off-target bypass mechanisms of acquired resistance to adagrasib in these patients.
“Diverse mechanisms confer resistance to the KRAS G12C inhibitors, including secondary KRAS mutations, MAP [mitogen-activated protein] kinase pathway alterations, acquired genomic rearrangements, and histologic transformation,” Dr. Awad said in a mini-symposium presentation.
“Several cases displayed multiple resistance mechanisms, and novel combinatorial strategies will be necessary to delay or overcome resistance in KRAS G12C-mutant cancers,” he said.
Inactivating KRAS
The KRAS G12C mutation is a glycine-to-cysteine substitution that results in the oncogene being switched on in its active form.
But the mutation has been considered too tough to target because of the KRAS gene’s strong binding affinity for guanosine triphosphate, an essential building block of RNA synthesis, and by a lack of accessible drug-binding sites.
Sotorasib and adagrasib are small-molecule, specific, and irreversible inhibitors of KRAS that interact with a “pocket” on the gene’s surface that is present only in an inactive conformation of KRAS. The drugs inhibit oncogenic signaling and tumorigenesis by preventing cycling of the oncogene into its active form.
Multiple mutations, histologic transformations
Dr. Awad and colleagues studied biopsy samples and circulating tumor DNA (ctDNA) from 30 patients both at baseline and after administration of adagrasib monotherapy. The patients all had initial responses to the drug but then experienced disease progression.
The investigators used mutagenesis screens to identify mechanisms of resistance to KRAS G12C inhibitors.
The 30 patients included 23 with NSCLC and 7 with CRC. Eighteen had unknown mechanisms of resistance, and putative resistance mechanisms were identified in the other 12 patients. Of this latter group, seven appeared to have single resistance mechanisms, and five had multiple mechanisms of resistance.
One patient with NSCLC who had radiographic evidence of response followed by progression was found to have had a novel KRAS Y96C mutation, and three had novel KRAS mutations in other gene regions, with multiple concurrent alterations in genes implicated in other forms of cancer, such as PTEN, BRAF, and MAP2K1.
The investigators also identified amplifications of the KRAS G12C allele, and MET.
In two patients, NSCLC underwent histologic transformation from adenocarcinoma at baseline to squamous cell carcinoma at the time of acquired resistance to the drug. No genomic resistance mechanisms were detected in either of these patients, Dr. Awad said.
“In several cases, we see multiple mechanisms or co-occurring alterations in each individual patient, with the suggestion that perhaps the multiple mutations or resistance mechanism may be more common in the colorectal population, particularly with acquired gene fusions, than in the lung cancer population, although larger datasets will be needed to confirm this observation,” he said.
Does duration of response matter?
In the question-and-answer session following his presentation, Dr. Awad was asked about clinical responses in the patients who developed resistance.
“In this initial reporting of resistance mechanisms we did not overlay or report out the clinical outcomes, including the durations of response or the time to disease progression, in part because this is an ongoing clinical trial, and those data will be reported in full at a later time,” Dr. Awad replied. “But I think it will be really important to identify whether patients are more likely to develop resistance earlier versus later or have different resistance mechanisms.”
Dr. Awad commented further that the resistance to adagrasib appeared to be acquired. “These resistance mutations were not detected to the level of detection at the baseline samples. So presumably they may be present at some low levels at the time of initial diagnosis, or they emerge over the course of therapy,” he said.
“Many of the resistance mechanisms appear to be more subclonal, occurring at an allele fraction lower than the original KRAS G12C mutation, which we know is the clonal event in the entire population of the cancer, and I think when we’re seeing these multiple resistance mechanisms emerging, they are potentially each representing different subclones that can develop simultaneously,” he added.
Adagrasib trials are supported by Mirati Therapeutics. Dr. Awad disclosed consulting for Mirati and others, and institutional research support from several different companies.
A version of this article first appeared on Medscape.com.
Hopes for a new category of agents recently hailed as “a triumph of drug discovery” have been dimmed somewhat by new data showing many types of acquired resistance.
KRAS is one of the most frequently mutated oncogenes in human cancer and has long been thought “undruggable” – but novel drugs acting specifically on the KRAS G12C mutation have shown promise in clinical trials.
Early results with the experimental KRAS inhibitors sotorasib and adagrasib were deemed promising, but new data presented at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract LB002) have splashed cold water on that enthusiasm.
The efficacy of these new drugs looks to be threatened by the development of resistance caused by a wide range of genomic and histologic mechanisms.
Mark M. Awad, MD, PhD, from the Dana-Farber Cancer Institute in Boston, reported data from 30 patients with non–small cell lung cancer (NSCLC) or colorectal cancer (CRC) bearing the KRAS G12C mutation who had disease progression while being treated with adagrasib in clinical trials. Investigators found multiple on-target KRAS alterations and off-target bypass mechanisms of acquired resistance to adagrasib in these patients.
“Diverse mechanisms confer resistance to the KRAS G12C inhibitors, including secondary KRAS mutations, MAP [mitogen-activated protein] kinase pathway alterations, acquired genomic rearrangements, and histologic transformation,” Dr. Awad said in a mini-symposium presentation.
“Several cases displayed multiple resistance mechanisms, and novel combinatorial strategies will be necessary to delay or overcome resistance in KRAS G12C-mutant cancers,” he said.
Inactivating KRAS
The KRAS G12C mutation is a glycine-to-cysteine substitution that results in the oncogene being switched on in its active form.
But the mutation has been considered too tough to target because of the KRAS gene’s strong binding affinity for guanosine triphosphate, an essential building block of RNA synthesis, and by a lack of accessible drug-binding sites.
Sotorasib and adagrasib are small-molecule, specific, and irreversible inhibitors of KRAS that interact with a “pocket” on the gene’s surface that is present only in an inactive conformation of KRAS. The drugs inhibit oncogenic signaling and tumorigenesis by preventing cycling of the oncogene into its active form.
Multiple mutations, histologic transformations
Dr. Awad and colleagues studied biopsy samples and circulating tumor DNA (ctDNA) from 30 patients both at baseline and after administration of adagrasib monotherapy. The patients all had initial responses to the drug but then experienced disease progression.
The investigators used mutagenesis screens to identify mechanisms of resistance to KRAS G12C inhibitors.
The 30 patients included 23 with NSCLC and 7 with CRC. Eighteen had unknown mechanisms of resistance, and putative resistance mechanisms were identified in the other 12 patients. Of this latter group, seven appeared to have single resistance mechanisms, and five had multiple mechanisms of resistance.
One patient with NSCLC who had radiographic evidence of response followed by progression was found to have had a novel KRAS Y96C mutation, and three had novel KRAS mutations in other gene regions, with multiple concurrent alterations in genes implicated in other forms of cancer, such as PTEN, BRAF, and MAP2K1.
The investigators also identified amplifications of the KRAS G12C allele, and MET.
In two patients, NSCLC underwent histologic transformation from adenocarcinoma at baseline to squamous cell carcinoma at the time of acquired resistance to the drug. No genomic resistance mechanisms were detected in either of these patients, Dr. Awad said.
“In several cases, we see multiple mechanisms or co-occurring alterations in each individual patient, with the suggestion that perhaps the multiple mutations or resistance mechanism may be more common in the colorectal population, particularly with acquired gene fusions, than in the lung cancer population, although larger datasets will be needed to confirm this observation,” he said.
Does duration of response matter?
In the question-and-answer session following his presentation, Dr. Awad was asked about clinical responses in the patients who developed resistance.
“In this initial reporting of resistance mechanisms we did not overlay or report out the clinical outcomes, including the durations of response or the time to disease progression, in part because this is an ongoing clinical trial, and those data will be reported in full at a later time,” Dr. Awad replied. “But I think it will be really important to identify whether patients are more likely to develop resistance earlier versus later or have different resistance mechanisms.”
Dr. Awad commented further that the resistance to adagrasib appeared to be acquired. “These resistance mutations were not detected to the level of detection at the baseline samples. So presumably they may be present at some low levels at the time of initial diagnosis, or they emerge over the course of therapy,” he said.
“Many of the resistance mechanisms appear to be more subclonal, occurring at an allele fraction lower than the original KRAS G12C mutation, which we know is the clonal event in the entire population of the cancer, and I think when we’re seeing these multiple resistance mechanisms emerging, they are potentially each representing different subclones that can develop simultaneously,” he added.
Adagrasib trials are supported by Mirati Therapeutics. Dr. Awad disclosed consulting for Mirati and others, and institutional research support from several different companies.
A version of this article first appeared on Medscape.com.
FROM AACR 2021
Personalized cancer vaccine shows early promise across tumor types
The vaccine, PGV-001, was given to 13 patients with solid tumors or multiple myeloma who had a high risk of recurrence after surgery or autologous stem cell transplant.
At last follow-up, four patients were still alive without evidence of disease and had not received subsequent therapy, four were alive and receiving therapy, three had died, and two were lost to follow-up.
Thomas Marron, MD, PhD , of Mount Sinai in New York presented these results in a poster at the American Association for Cancer Research Annual Meeting 2021: Week 1 ( Abstract LB048 ). Data in the abstract differ from the data presented.
“While cancer immunotherapy has revolutionized the treatment of cancer, we know that the majority of patients fail to achieve significant clinical response,” Dr. Marron said during his presentation. “One reason for this may be due to lack of preexisting primed T-cell response needed for PD-1 blockade to have a significant effect. To address this, personalized neoantigen vaccines may help prime an improved immune response against tumor cells.”
With this in mind, Dr. Marron and colleagues developed PGV-001, a vaccine consisting of patient-specific synthetic neoantigen peptides given to patients in the adjuvant setting.
Creating a personalized vaccine
The researchers synthesized PGV-001 for 15 patients with advanced malignancies. The patients first underwent tumor and germline DNA sequencing as well as HLA typing. Bulk RNA sequencing was performed on patients’ tumors as well.
Then, the researchers used a computational pipeline called OpenVax to identify candidate neoantigens. This pipeline, developed at Mount Sinai, identified and prioritized candidate neoantigens using predicted MHC class I binding affinity and neoantigen abundance.
OpenVax identified an average of 71.5 neoantigens per patient (range, 7-193). The goal was to synthesize a maximum of 10 peptides per patient, but two patients did not have an adequate number of neoantigens.
Vaccine administration
The peptides were administered over the course of 27 weeks along with poly-ICLC and a tetanus helper peptide. Before receiving their vaccine doses, patients with solid tumors had undergone curative-intent surgery, and those with multiple myeloma had undergone autologous stem cell transplant.
“Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have less cancer spread,” principal investigator Nina Bhardwaj, MD, PhD , of Mount Sinai, explained in a press release .
“We have, therefore, developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, such as surgery in solid tumors and bone marrow transplant in multiple myeloma, when patients have minimal, typically microscopic, residual disease.”
Feasibility, safety, and immunogenicity
PGV-001 was synthesized for 15 patients and administered to 13 of them. Six of the 13 patients had head and neck squamous cell carcinoma, three had multiple myeloma, two had non–small cell lung cancer, one had breast cancer, and one had urothelial carcinoma.
Eleven patients received all 10 intended doses, and two patients received at least 8 doses.
“The vaccine was well tolerated, with only half of patients experiencing mild, grade 1 adverse events,” Dr. Marron said.
Transient injection site reactions occurred in four patients, and grade 1 fever was reported in one patient.
Immune monitoring is ongoing, but an initial analysis in one patient showed “robust responses” in CD4 and CD8 T cells by intracellular cytokine staining for interferon-gamma, tumor necrosis factor–alpha, and interleukin-2 after in vitro expansion in the presence of vaccine antigens, according to the researchers.
Dr. Marron noted that robust T-cell reactivity was seen at the completion of all 10 doses but was not seen after the 6th dose, and this supports the need for a prolonged dosing schedule.
Survival and subsequent therapy
At a mean follow-up of 880 days, four patients had no evidence of disease and had not received subsequent therapy. This includes one patient with stage IIIA non–small cell lung cancer, one with stage IVA HER-2 positive breast cancer, one with stage II urothelial carcinoma, and one with multiple myeloma.
Four patients were alive and receiving subsequent lines of therapy. Two of these patients had significant responses to anti–PD-1 therapy.
Three patients have died, two of whom had documented recurrence of their malignancy. The last two patients were lost to follow-up without documented recurrence.
“Our results demonstrate that the OpenVax pipeline is a viable approach to generate a safe, personalized cancer vaccine, which could potentially be used to treat a range of tumor types,” Dr. Bhardwaj said.
Trials combining neoantigens identified with the OpenVax platform are ongoing in patients with urothelial carcinoma and glioblastoma multiforme, Dr. Marron said.
The current study ( NCT02721043 ) is sponsored by Dr. Bhardwaj. Dr. Marron and Dr. Bhardwaj reported having no disclosures. Their colleagues disclosed relationships with Bristol Myers Squibb, Sema4, and Related Sciences.
The vaccine, PGV-001, was given to 13 patients with solid tumors or multiple myeloma who had a high risk of recurrence after surgery or autologous stem cell transplant.
At last follow-up, four patients were still alive without evidence of disease and had not received subsequent therapy, four were alive and receiving therapy, three had died, and two were lost to follow-up.
Thomas Marron, MD, PhD , of Mount Sinai in New York presented these results in a poster at the American Association for Cancer Research Annual Meeting 2021: Week 1 ( Abstract LB048 ). Data in the abstract differ from the data presented.
“While cancer immunotherapy has revolutionized the treatment of cancer, we know that the majority of patients fail to achieve significant clinical response,” Dr. Marron said during his presentation. “One reason for this may be due to lack of preexisting primed T-cell response needed for PD-1 blockade to have a significant effect. To address this, personalized neoantigen vaccines may help prime an improved immune response against tumor cells.”
With this in mind, Dr. Marron and colleagues developed PGV-001, a vaccine consisting of patient-specific synthetic neoantigen peptides given to patients in the adjuvant setting.
Creating a personalized vaccine
The researchers synthesized PGV-001 for 15 patients with advanced malignancies. The patients first underwent tumor and germline DNA sequencing as well as HLA typing. Bulk RNA sequencing was performed on patients’ tumors as well.
Then, the researchers used a computational pipeline called OpenVax to identify candidate neoantigens. This pipeline, developed at Mount Sinai, identified and prioritized candidate neoantigens using predicted MHC class I binding affinity and neoantigen abundance.
OpenVax identified an average of 71.5 neoantigens per patient (range, 7-193). The goal was to synthesize a maximum of 10 peptides per patient, but two patients did not have an adequate number of neoantigens.
Vaccine administration
The peptides were administered over the course of 27 weeks along with poly-ICLC and a tetanus helper peptide. Before receiving their vaccine doses, patients with solid tumors had undergone curative-intent surgery, and those with multiple myeloma had undergone autologous stem cell transplant.
“Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have less cancer spread,” principal investigator Nina Bhardwaj, MD, PhD , of Mount Sinai, explained in a press release .
“We have, therefore, developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, such as surgery in solid tumors and bone marrow transplant in multiple myeloma, when patients have minimal, typically microscopic, residual disease.”
Feasibility, safety, and immunogenicity
PGV-001 was synthesized for 15 patients and administered to 13 of them. Six of the 13 patients had head and neck squamous cell carcinoma, three had multiple myeloma, two had non–small cell lung cancer, one had breast cancer, and one had urothelial carcinoma.
Eleven patients received all 10 intended doses, and two patients received at least 8 doses.
“The vaccine was well tolerated, with only half of patients experiencing mild, grade 1 adverse events,” Dr. Marron said.
Transient injection site reactions occurred in four patients, and grade 1 fever was reported in one patient.
Immune monitoring is ongoing, but an initial analysis in one patient showed “robust responses” in CD4 and CD8 T cells by intracellular cytokine staining for interferon-gamma, tumor necrosis factor–alpha, and interleukin-2 after in vitro expansion in the presence of vaccine antigens, according to the researchers.
Dr. Marron noted that robust T-cell reactivity was seen at the completion of all 10 doses but was not seen after the 6th dose, and this supports the need for a prolonged dosing schedule.
Survival and subsequent therapy
At a mean follow-up of 880 days, four patients had no evidence of disease and had not received subsequent therapy. This includes one patient with stage IIIA non–small cell lung cancer, one with stage IVA HER-2 positive breast cancer, one with stage II urothelial carcinoma, and one with multiple myeloma.
Four patients were alive and receiving subsequent lines of therapy. Two of these patients had significant responses to anti–PD-1 therapy.
Three patients have died, two of whom had documented recurrence of their malignancy. The last two patients were lost to follow-up without documented recurrence.
“Our results demonstrate that the OpenVax pipeline is a viable approach to generate a safe, personalized cancer vaccine, which could potentially be used to treat a range of tumor types,” Dr. Bhardwaj said.
Trials combining neoantigens identified with the OpenVax platform are ongoing in patients with urothelial carcinoma and glioblastoma multiforme, Dr. Marron said.
The current study ( NCT02721043 ) is sponsored by Dr. Bhardwaj. Dr. Marron and Dr. Bhardwaj reported having no disclosures. Their colleagues disclosed relationships with Bristol Myers Squibb, Sema4, and Related Sciences.
The vaccine, PGV-001, was given to 13 patients with solid tumors or multiple myeloma who had a high risk of recurrence after surgery or autologous stem cell transplant.
At last follow-up, four patients were still alive without evidence of disease and had not received subsequent therapy, four were alive and receiving therapy, three had died, and two were lost to follow-up.
Thomas Marron, MD, PhD , of Mount Sinai in New York presented these results in a poster at the American Association for Cancer Research Annual Meeting 2021: Week 1 ( Abstract LB048 ). Data in the abstract differ from the data presented.
“While cancer immunotherapy has revolutionized the treatment of cancer, we know that the majority of patients fail to achieve significant clinical response,” Dr. Marron said during his presentation. “One reason for this may be due to lack of preexisting primed T-cell response needed for PD-1 blockade to have a significant effect. To address this, personalized neoantigen vaccines may help prime an improved immune response against tumor cells.”
With this in mind, Dr. Marron and colleagues developed PGV-001, a vaccine consisting of patient-specific synthetic neoantigen peptides given to patients in the adjuvant setting.
Creating a personalized vaccine
The researchers synthesized PGV-001 for 15 patients with advanced malignancies. The patients first underwent tumor and germline DNA sequencing as well as HLA typing. Bulk RNA sequencing was performed on patients’ tumors as well.
Then, the researchers used a computational pipeline called OpenVax to identify candidate neoantigens. This pipeline, developed at Mount Sinai, identified and prioritized candidate neoantigens using predicted MHC class I binding affinity and neoantigen abundance.
OpenVax identified an average of 71.5 neoantigens per patient (range, 7-193). The goal was to synthesize a maximum of 10 peptides per patient, but two patients did not have an adequate number of neoantigens.
Vaccine administration
The peptides were administered over the course of 27 weeks along with poly-ICLC and a tetanus helper peptide. Before receiving their vaccine doses, patients with solid tumors had undergone curative-intent surgery, and those with multiple myeloma had undergone autologous stem cell transplant.
“Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have less cancer spread,” principal investigator Nina Bhardwaj, MD, PhD , of Mount Sinai, explained in a press release .
“We have, therefore, developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, such as surgery in solid tumors and bone marrow transplant in multiple myeloma, when patients have minimal, typically microscopic, residual disease.”
Feasibility, safety, and immunogenicity
PGV-001 was synthesized for 15 patients and administered to 13 of them. Six of the 13 patients had head and neck squamous cell carcinoma, three had multiple myeloma, two had non–small cell lung cancer, one had breast cancer, and one had urothelial carcinoma.
Eleven patients received all 10 intended doses, and two patients received at least 8 doses.
“The vaccine was well tolerated, with only half of patients experiencing mild, grade 1 adverse events,” Dr. Marron said.
Transient injection site reactions occurred in four patients, and grade 1 fever was reported in one patient.
Immune monitoring is ongoing, but an initial analysis in one patient showed “robust responses” in CD4 and CD8 T cells by intracellular cytokine staining for interferon-gamma, tumor necrosis factor–alpha, and interleukin-2 after in vitro expansion in the presence of vaccine antigens, according to the researchers.
Dr. Marron noted that robust T-cell reactivity was seen at the completion of all 10 doses but was not seen after the 6th dose, and this supports the need for a prolonged dosing schedule.
Survival and subsequent therapy
At a mean follow-up of 880 days, four patients had no evidence of disease and had not received subsequent therapy. This includes one patient with stage IIIA non–small cell lung cancer, one with stage IVA HER-2 positive breast cancer, one with stage II urothelial carcinoma, and one with multiple myeloma.
Four patients were alive and receiving subsequent lines of therapy. Two of these patients had significant responses to anti–PD-1 therapy.
Three patients have died, two of whom had documented recurrence of their malignancy. The last two patients were lost to follow-up without documented recurrence.
“Our results demonstrate that the OpenVax pipeline is a viable approach to generate a safe, personalized cancer vaccine, which could potentially be used to treat a range of tumor types,” Dr. Bhardwaj said.
Trials combining neoantigens identified with the OpenVax platform are ongoing in patients with urothelial carcinoma and glioblastoma multiforme, Dr. Marron said.
The current study ( NCT02721043 ) is sponsored by Dr. Bhardwaj. Dr. Marron and Dr. Bhardwaj reported having no disclosures. Their colleagues disclosed relationships with Bristol Myers Squibb, Sema4, and Related Sciences.
FROM AACR 2021
Steroid-refractory pneumonitis from ICIs: Experience at major centers
Pneumonitis is an uncommon and potentially life-threatening complication of immune checkpoint inhibitor (ICI) therapy. A fraction of patients with ICI-related pneumonitis fail to respond to initial therapy with high-dose systemic steroids.
The recently published experiences at two major cancer centers shed light on the outcomes from treatment and can provide some advice to clinicians for dealing with affected patients.
The Johns Hopkins experience
Because ICI-related pneumonitis typically improves within 48-72 hours of steroid therapy, at Johns Hopkins University, Baltimore, steroid-refractory pneumonitis is defined as pneumonitis that demonstrates no clinical improvement after high-dose corticosteroids for 2-14 days. If the immune toxicity–specialized, multidisciplinary management team implements additional immunosuppressive therapy, that is regarded as confirmatory evidence.
Aanika Balaji, a medical student at Johns Hopkins University, and colleagues retrospectively summarized the clinical course of 12 patients with ICI-related pneumonitis between 2011 and 2020. Clinical improvement with subsequent treatment was evidenced by reduction in either level of care or oxygen requirements.
Three-quarters of the patients were current or former smokers, and the same proportion had lung cancer. Most patients (91.6%) had received chemotherapy, 58.3% had prior chest radiotherapy, and 58.3% had achieved partial response or stable disease with an ICI.
Steroid-refractory ICI-related pneumonitis developed between 40 and 127 days (median, 85 days) after the first dose of ICI therapy. Subsequent immunosuppressive management included IVIg, infliximab, or the combination, in addition to ICU-level supportive care.
Among the seven patients who received IVIg alone, two patients (29%) achieved clinical improvement and hospital discharge. The remainder died.
The two patients treated with infliximab and the three patients treated with sequential IVIg and infliximab died. All deaths were attributed to ICI-related pneumonitis or infectious complications.
Overall, clinically relevant findings were:
- Steroid-refractory ICI-related pneumonitis was seen in 18.5% of patients referred for multidisciplinary care.
- Steroid-refractory ICI-related pneumonitis occurred at a median of 85 days into a patient’s ICI treatment.
- Some patients improved clinically after IVIg therapy, but mortality was high overall.
- Infliximab therapy, alone or in combination with IVIg, was ineffective.
The Memorial Sloan Kettering experience
Jason Beattie, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues performed a retrospective study of patients who had pneumonitis after ICI therapy and/or received immune modulator therapy after corticosteroids in the setting of ICI cancer treatment.
Manual record review was performed to exclude cases of pneumonitis from other causes. The period reviewed was roughly contemporaneous with the Johns Hopkins series.
Patients with ICI-related pneumonitis were divided into “steroid refractory” (i.e., no response to high-dose corticosteroids) or “steroid resistant” (i.e., initial response, followed by worsening) categories.
The researchers identified 26 patients with ICI-related pneumonitis, all of whom had advanced malignancy (8 lung cancer, 4 malignant melanoma, 4 renal cell cancer, and 10 “other” cancers).
A majority of patients (85%) were current or former smokers, 73% had received ICI monotherapy, 35% had received prior chest radiation at a median interval of 4.9 months prior to pneumonitis onset, and 27% had preexisting pulmonary disease.
Twelve patients (46%) had steroid-refractory ICI-related pneumonitis, and 14 (54%) had steroid-resistant ICI-related pneumonitis.
The two groups differed in time to pneumonitis onset (a median of 68 days in the refractory group and 182 days in the resistant group) and time to immune modulator therapy after beginning steroids (median 7 days and 2.9 months, respectively). In the steroid-refractory cases, pneumonitis was more severe.
In addition to corticosteroids, most patients received infliximab monotherapy or infliximab with mycophenolate mofetil. In contrast to the Johns Hopkins series, IVIg was not used in the Memorial Sloan Kettering cases.
Outcomes from immune modulators were graded based on clinical evidence (progress notes, oxygen requirements, level of care, radiologic information, etc.) of resolution of pneumonitis on imaging at least 8 weeks after cessation of steroids and immune modulator therapy, durable improvement for at least 8 weeks after immune modulator therapy, transient improvement followed by pneumonitis relapse or inadequate follow-up because of death or hospice referral, or no improvement.
Ten patients (38%) had durable improvement of ICI-related pneumonitis, of whom three (12%) had complete resolution. Two of the patients with complete resolution had steroid-refractory pneumonitis, both of whom had received infliximab followed by mycophenolate mofetil.
Among the seven patients with durable improvement, four remained alive on immune modulators. Time to resolution of pneumonitis was protracted, ranging from 2.3 months to 8.4 months in the steroid-refractory patients.
Durable response was less common with steroid-refractory (25%) than steroid-resistant (50%) disease, with a significant difference in 90-day survival of 25% and 71%, respectively.
Among the 13 (50%) patients with transient improvement in ICI-related pneumonitis, 8 ultimately died, either because of recurrent ICI-related pneumonitis or infection. All three patients with no improvement from immune modulators died.
The 90-day all-cause mortality was 50%, with durable pneumonitis improvement and freedom from severe infectious complications occurring in only about a third of patients.
Lessons for clinicians
The National Comprehensive Cancer Network, the Society for Immunotherapy of Cancer, and the European Society of Medical Oncology have all published guidelines and recommendations for immunosuppression for steroid-refractory adverse events from ICIs.
Unfortunately, there is little experience with steroid-unresponsive ICI-related pneumonitis. The ideal sequence, dose, and duration of additional immune modulator therapy for ICI-related pneumonitis are unclear and may differ from the approaches to other immune-related toxicities.
This is important because, as suggested in an editorial by Margaret Gatti-Mays, MD, and James L. Gulley, MD, PhD, it is likely that ICI-related pneumonitis will be seen more in routine practice than in clinical trial populations. In addition, across all tumor types, ICI-related pneumonitis is the most common cause of ICI-associated death from toxicity.
The retrospective studies from Johns Hopkins and Memorial Sloan Kettering constitute the largest published experience with ICI-related pneumonitis and yield important clinical insights.
Uniform definitions of potentially important patient subgroups (e.g., steroid refractory vs. steroid resistant) are needed. The steroid-refractory and steroid-resistant subgroups have distinctly different clinical features and outcomes. Uniformity in the subgroup definitions would be a useful starting point from both clinical and research perspectives.
Preferred treatment choices need to be tested systematically in multi-institutional studies. Any potential impact of treatment for ICI-related pneumonitis on antitumor immune control should be identified.
Endpoints of interest need to be defined and measured prospectively. All-cause mortality after 90 days is important, but, as the authors of both reviews noted, there are vitally important narratives and differences in functionality that are completely concealed by restricting the focus to mortality.
Potential causal relationships with antecedent exposure to tobacco, radiation, intrathoracic tumor burden, or other factors need to be defined.
Clinicians need predictive biomarkers for ICI-related pneumonitis (e.g., in peripheral blood, pulmonary function testing, or bronchoscopy specimens). At-risk patients may benefit from early intervention.
The limitations of single-institution record reviews in guiding real-world patient management notwithstanding, these reviews illustrate the value of registries and prospective studies to guide the path forward. Taking these next steps will ensure for our patients that the success of immune-targeted therapy against their cancer never becomes a Pyrrhic victory.
The Johns Hopkins investigators and the editorialists reported having no disclosures. The Memorial Sloan Kettering investigators disclosed relationships with Targeted Oncology, Merck, Array BioPharma, Novartis, and many other companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Pneumonitis is an uncommon and potentially life-threatening complication of immune checkpoint inhibitor (ICI) therapy. A fraction of patients with ICI-related pneumonitis fail to respond to initial therapy with high-dose systemic steroids.
The recently published experiences at two major cancer centers shed light on the outcomes from treatment and can provide some advice to clinicians for dealing with affected patients.
The Johns Hopkins experience
Because ICI-related pneumonitis typically improves within 48-72 hours of steroid therapy, at Johns Hopkins University, Baltimore, steroid-refractory pneumonitis is defined as pneumonitis that demonstrates no clinical improvement after high-dose corticosteroids for 2-14 days. If the immune toxicity–specialized, multidisciplinary management team implements additional immunosuppressive therapy, that is regarded as confirmatory evidence.
Aanika Balaji, a medical student at Johns Hopkins University, and colleagues retrospectively summarized the clinical course of 12 patients with ICI-related pneumonitis between 2011 and 2020. Clinical improvement with subsequent treatment was evidenced by reduction in either level of care or oxygen requirements.
Three-quarters of the patients were current or former smokers, and the same proportion had lung cancer. Most patients (91.6%) had received chemotherapy, 58.3% had prior chest radiotherapy, and 58.3% had achieved partial response or stable disease with an ICI.
Steroid-refractory ICI-related pneumonitis developed between 40 and 127 days (median, 85 days) after the first dose of ICI therapy. Subsequent immunosuppressive management included IVIg, infliximab, or the combination, in addition to ICU-level supportive care.
Among the seven patients who received IVIg alone, two patients (29%) achieved clinical improvement and hospital discharge. The remainder died.
The two patients treated with infliximab and the three patients treated with sequential IVIg and infliximab died. All deaths were attributed to ICI-related pneumonitis or infectious complications.
Overall, clinically relevant findings were:
- Steroid-refractory ICI-related pneumonitis was seen in 18.5% of patients referred for multidisciplinary care.
- Steroid-refractory ICI-related pneumonitis occurred at a median of 85 days into a patient’s ICI treatment.
- Some patients improved clinically after IVIg therapy, but mortality was high overall.
- Infliximab therapy, alone or in combination with IVIg, was ineffective.
The Memorial Sloan Kettering experience
Jason Beattie, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues performed a retrospective study of patients who had pneumonitis after ICI therapy and/or received immune modulator therapy after corticosteroids in the setting of ICI cancer treatment.
Manual record review was performed to exclude cases of pneumonitis from other causes. The period reviewed was roughly contemporaneous with the Johns Hopkins series.
Patients with ICI-related pneumonitis were divided into “steroid refractory” (i.e., no response to high-dose corticosteroids) or “steroid resistant” (i.e., initial response, followed by worsening) categories.
The researchers identified 26 patients with ICI-related pneumonitis, all of whom had advanced malignancy (8 lung cancer, 4 malignant melanoma, 4 renal cell cancer, and 10 “other” cancers).
A majority of patients (85%) were current or former smokers, 73% had received ICI monotherapy, 35% had received prior chest radiation at a median interval of 4.9 months prior to pneumonitis onset, and 27% had preexisting pulmonary disease.
Twelve patients (46%) had steroid-refractory ICI-related pneumonitis, and 14 (54%) had steroid-resistant ICI-related pneumonitis.
The two groups differed in time to pneumonitis onset (a median of 68 days in the refractory group and 182 days in the resistant group) and time to immune modulator therapy after beginning steroids (median 7 days and 2.9 months, respectively). In the steroid-refractory cases, pneumonitis was more severe.
In addition to corticosteroids, most patients received infliximab monotherapy or infliximab with mycophenolate mofetil. In contrast to the Johns Hopkins series, IVIg was not used in the Memorial Sloan Kettering cases.
Outcomes from immune modulators were graded based on clinical evidence (progress notes, oxygen requirements, level of care, radiologic information, etc.) of resolution of pneumonitis on imaging at least 8 weeks after cessation of steroids and immune modulator therapy, durable improvement for at least 8 weeks after immune modulator therapy, transient improvement followed by pneumonitis relapse or inadequate follow-up because of death or hospice referral, or no improvement.
Ten patients (38%) had durable improvement of ICI-related pneumonitis, of whom three (12%) had complete resolution. Two of the patients with complete resolution had steroid-refractory pneumonitis, both of whom had received infliximab followed by mycophenolate mofetil.
Among the seven patients with durable improvement, four remained alive on immune modulators. Time to resolution of pneumonitis was protracted, ranging from 2.3 months to 8.4 months in the steroid-refractory patients.
Durable response was less common with steroid-refractory (25%) than steroid-resistant (50%) disease, with a significant difference in 90-day survival of 25% and 71%, respectively.
Among the 13 (50%) patients with transient improvement in ICI-related pneumonitis, 8 ultimately died, either because of recurrent ICI-related pneumonitis or infection. All three patients with no improvement from immune modulators died.
The 90-day all-cause mortality was 50%, with durable pneumonitis improvement and freedom from severe infectious complications occurring in only about a third of patients.
Lessons for clinicians
The National Comprehensive Cancer Network, the Society for Immunotherapy of Cancer, and the European Society of Medical Oncology have all published guidelines and recommendations for immunosuppression for steroid-refractory adverse events from ICIs.
Unfortunately, there is little experience with steroid-unresponsive ICI-related pneumonitis. The ideal sequence, dose, and duration of additional immune modulator therapy for ICI-related pneumonitis are unclear and may differ from the approaches to other immune-related toxicities.
This is important because, as suggested in an editorial by Margaret Gatti-Mays, MD, and James L. Gulley, MD, PhD, it is likely that ICI-related pneumonitis will be seen more in routine practice than in clinical trial populations. In addition, across all tumor types, ICI-related pneumonitis is the most common cause of ICI-associated death from toxicity.
The retrospective studies from Johns Hopkins and Memorial Sloan Kettering constitute the largest published experience with ICI-related pneumonitis and yield important clinical insights.
Uniform definitions of potentially important patient subgroups (e.g., steroid refractory vs. steroid resistant) are needed. The steroid-refractory and steroid-resistant subgroups have distinctly different clinical features and outcomes. Uniformity in the subgroup definitions would be a useful starting point from both clinical and research perspectives.
Preferred treatment choices need to be tested systematically in multi-institutional studies. Any potential impact of treatment for ICI-related pneumonitis on antitumor immune control should be identified.
Endpoints of interest need to be defined and measured prospectively. All-cause mortality after 90 days is important, but, as the authors of both reviews noted, there are vitally important narratives and differences in functionality that are completely concealed by restricting the focus to mortality.
Potential causal relationships with antecedent exposure to tobacco, radiation, intrathoracic tumor burden, or other factors need to be defined.
Clinicians need predictive biomarkers for ICI-related pneumonitis (e.g., in peripheral blood, pulmonary function testing, or bronchoscopy specimens). At-risk patients may benefit from early intervention.
The limitations of single-institution record reviews in guiding real-world patient management notwithstanding, these reviews illustrate the value of registries and prospective studies to guide the path forward. Taking these next steps will ensure for our patients that the success of immune-targeted therapy against their cancer never becomes a Pyrrhic victory.
The Johns Hopkins investigators and the editorialists reported having no disclosures. The Memorial Sloan Kettering investigators disclosed relationships with Targeted Oncology, Merck, Array BioPharma, Novartis, and many other companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Pneumonitis is an uncommon and potentially life-threatening complication of immune checkpoint inhibitor (ICI) therapy. A fraction of patients with ICI-related pneumonitis fail to respond to initial therapy with high-dose systemic steroids.
The recently published experiences at two major cancer centers shed light on the outcomes from treatment and can provide some advice to clinicians for dealing with affected patients.
The Johns Hopkins experience
Because ICI-related pneumonitis typically improves within 48-72 hours of steroid therapy, at Johns Hopkins University, Baltimore, steroid-refractory pneumonitis is defined as pneumonitis that demonstrates no clinical improvement after high-dose corticosteroids for 2-14 days. If the immune toxicity–specialized, multidisciplinary management team implements additional immunosuppressive therapy, that is regarded as confirmatory evidence.
Aanika Balaji, a medical student at Johns Hopkins University, and colleagues retrospectively summarized the clinical course of 12 patients with ICI-related pneumonitis between 2011 and 2020. Clinical improvement with subsequent treatment was evidenced by reduction in either level of care or oxygen requirements.
Three-quarters of the patients were current or former smokers, and the same proportion had lung cancer. Most patients (91.6%) had received chemotherapy, 58.3% had prior chest radiotherapy, and 58.3% had achieved partial response or stable disease with an ICI.
Steroid-refractory ICI-related pneumonitis developed between 40 and 127 days (median, 85 days) after the first dose of ICI therapy. Subsequent immunosuppressive management included IVIg, infliximab, or the combination, in addition to ICU-level supportive care.
Among the seven patients who received IVIg alone, two patients (29%) achieved clinical improvement and hospital discharge. The remainder died.
The two patients treated with infliximab and the three patients treated with sequential IVIg and infliximab died. All deaths were attributed to ICI-related pneumonitis or infectious complications.
Overall, clinically relevant findings were:
- Steroid-refractory ICI-related pneumonitis was seen in 18.5% of patients referred for multidisciplinary care.
- Steroid-refractory ICI-related pneumonitis occurred at a median of 85 days into a patient’s ICI treatment.
- Some patients improved clinically after IVIg therapy, but mortality was high overall.
- Infliximab therapy, alone or in combination with IVIg, was ineffective.
The Memorial Sloan Kettering experience
Jason Beattie, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues performed a retrospective study of patients who had pneumonitis after ICI therapy and/or received immune modulator therapy after corticosteroids in the setting of ICI cancer treatment.
Manual record review was performed to exclude cases of pneumonitis from other causes. The period reviewed was roughly contemporaneous with the Johns Hopkins series.
Patients with ICI-related pneumonitis were divided into “steroid refractory” (i.e., no response to high-dose corticosteroids) or “steroid resistant” (i.e., initial response, followed by worsening) categories.
The researchers identified 26 patients with ICI-related pneumonitis, all of whom had advanced malignancy (8 lung cancer, 4 malignant melanoma, 4 renal cell cancer, and 10 “other” cancers).
A majority of patients (85%) were current or former smokers, 73% had received ICI monotherapy, 35% had received prior chest radiation at a median interval of 4.9 months prior to pneumonitis onset, and 27% had preexisting pulmonary disease.
Twelve patients (46%) had steroid-refractory ICI-related pneumonitis, and 14 (54%) had steroid-resistant ICI-related pneumonitis.
The two groups differed in time to pneumonitis onset (a median of 68 days in the refractory group and 182 days in the resistant group) and time to immune modulator therapy after beginning steroids (median 7 days and 2.9 months, respectively). In the steroid-refractory cases, pneumonitis was more severe.
In addition to corticosteroids, most patients received infliximab monotherapy or infliximab with mycophenolate mofetil. In contrast to the Johns Hopkins series, IVIg was not used in the Memorial Sloan Kettering cases.
Outcomes from immune modulators were graded based on clinical evidence (progress notes, oxygen requirements, level of care, radiologic information, etc.) of resolution of pneumonitis on imaging at least 8 weeks after cessation of steroids and immune modulator therapy, durable improvement for at least 8 weeks after immune modulator therapy, transient improvement followed by pneumonitis relapse or inadequate follow-up because of death or hospice referral, or no improvement.
Ten patients (38%) had durable improvement of ICI-related pneumonitis, of whom three (12%) had complete resolution. Two of the patients with complete resolution had steroid-refractory pneumonitis, both of whom had received infliximab followed by mycophenolate mofetil.
Among the seven patients with durable improvement, four remained alive on immune modulators. Time to resolution of pneumonitis was protracted, ranging from 2.3 months to 8.4 months in the steroid-refractory patients.
Durable response was less common with steroid-refractory (25%) than steroid-resistant (50%) disease, with a significant difference in 90-day survival of 25% and 71%, respectively.
Among the 13 (50%) patients with transient improvement in ICI-related pneumonitis, 8 ultimately died, either because of recurrent ICI-related pneumonitis or infection. All three patients with no improvement from immune modulators died.
The 90-day all-cause mortality was 50%, with durable pneumonitis improvement and freedom from severe infectious complications occurring in only about a third of patients.
Lessons for clinicians
The National Comprehensive Cancer Network, the Society for Immunotherapy of Cancer, and the European Society of Medical Oncology have all published guidelines and recommendations for immunosuppression for steroid-refractory adverse events from ICIs.
Unfortunately, there is little experience with steroid-unresponsive ICI-related pneumonitis. The ideal sequence, dose, and duration of additional immune modulator therapy for ICI-related pneumonitis are unclear and may differ from the approaches to other immune-related toxicities.
This is important because, as suggested in an editorial by Margaret Gatti-Mays, MD, and James L. Gulley, MD, PhD, it is likely that ICI-related pneumonitis will be seen more in routine practice than in clinical trial populations. In addition, across all tumor types, ICI-related pneumonitis is the most common cause of ICI-associated death from toxicity.
The retrospective studies from Johns Hopkins and Memorial Sloan Kettering constitute the largest published experience with ICI-related pneumonitis and yield important clinical insights.
Uniform definitions of potentially important patient subgroups (e.g., steroid refractory vs. steroid resistant) are needed. The steroid-refractory and steroid-resistant subgroups have distinctly different clinical features and outcomes. Uniformity in the subgroup definitions would be a useful starting point from both clinical and research perspectives.
Preferred treatment choices need to be tested systematically in multi-institutional studies. Any potential impact of treatment for ICI-related pneumonitis on antitumor immune control should be identified.
Endpoints of interest need to be defined and measured prospectively. All-cause mortality after 90 days is important, but, as the authors of both reviews noted, there are vitally important narratives and differences in functionality that are completely concealed by restricting the focus to mortality.
Potential causal relationships with antecedent exposure to tobacco, radiation, intrathoracic tumor burden, or other factors need to be defined.
Clinicians need predictive biomarkers for ICI-related pneumonitis (e.g., in peripheral blood, pulmonary function testing, or bronchoscopy specimens). At-risk patients may benefit from early intervention.
The limitations of single-institution record reviews in guiding real-world patient management notwithstanding, these reviews illustrate the value of registries and prospective studies to guide the path forward. Taking these next steps will ensure for our patients that the success of immune-targeted therapy against their cancer never becomes a Pyrrhic victory.
The Johns Hopkins investigators and the editorialists reported having no disclosures. The Memorial Sloan Kettering investigators disclosed relationships with Targeted Oncology, Merck, Array BioPharma, Novartis, and many other companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Palliative care helpful but underutilized for blood cancer patients
Specialty palliative care interventions improve outcomes in patients with hematologic malignancies but are underutilized, according to findings from a systematic literature review.
Outcomes that were improved, as demonstrated by 16 studies that met inclusion criteria for the review, included symptom management, inpatient mortality, health care utilization, health care costs, and caregiver-reported outcomes, Elizabeth Elliott, DO, a hematology and oncology fellow at the Cardinal Bernardin Cancer Center, Loyola University, Maywood, Ill., and colleagues reported.
The findings were published online in the Journal of Pain and Symptom Management.
Palliative care needs
Patients with hematologic malignancies, including leukemia, myeloma, and lymphoma, have a high need for supportive care, the authors noted, adding that, although its use has increased over time, palliative care (PC) is often provided late in the disease course – sometimes only in the final days of life.
“Compared with their solid tumor counterparts, patients with hematologic malignancies experience higher symptom burdens, have higher rates of cancer-directed care near death, and are more likely to die while hospitalized than at home or in hospice,” they wrote. “Despite this need, specialist palliative care is less commonly utilized in patients with hematologic malignancies than other cancer types.”
Given the high health care utilization among patients with hematologic malignancies, earlier and more widespread utilization of PC in this population may significantly reduce health care costs, they added.
Palliative care benefits
Of 5,345 studies published between 2005 and 2020 and screened for the current review, 16 met inclusion criteria, including 10 retrospective cohort studies; 4 prospective cohort studies; and 2 randomized, controlled studies.
Nine studies included only patients with hematologic malignancies and seven included both patients with solid tumors and patients with hematologic malignancies. Each study assessed as being of moderate quality.
Benefits of PC as demonstrated in the studies included:
Symptom management: One study, for example, showed that an integrated psychological and PC intervention improved traumatic stress levels, degree and number of physical symptoms, pain intensity, depressive symptoms, and quality of life, compared with no intervention. Another showed that the percentage of patients reporting moderate to severe pain improved from 57% to 18% with a PC intervention, and the number reporting depressive episodes improved from 13% to 5%.
Reduced in-patient death: Findings from eight studies showed that 21.9%-83% of those receiving PC died at home, compared with 6.0%-8.9% of controls. Two studies showed that PC provided at least 20 days prior to death decreased the likelihood of inpatient death and death in an ICU, compared with controls, and one showed that the rate of in-hospital deaths was 30% for those with home PC or hospice, compared with 80% of controls.
Health care utilization: The studies showed that hospitalization occurred in 45%-76.3% of hematologic malignancy patients who received PC, compared with 98% of controls. The odds ratio for hospitalization among acute leukemia patients receiving PC was 0.64, compared with 2.53 among those in a historical control group.
Caregiver-reported outcomes: One randomized, controlled study showed that PC was associated with smaller increases in depression scores, improved coping, and improved scores in multiple quality of life domains in caregivers versus controls.
Survival: One study showed that a larger percentage of hematologic malignancy patients who died 1-6 months after diagnosis had not received PC (28% vs. 23%), whereas more of those who died 6-12 months or 12 or more months after diagnosis had received PC (23.9 vs. 14.9% and 42.5% vs. 22.0%).
Health care costs: Two studies showed a decrease in inpatient costs after a palliative care consultation. Decreases in hospitalization costs were $2,321 and $1,506 for less medically complex patients and $3,515 and $5,617 for more medically complex patient.
Improving PC utilization
One potential strategy to promote earlier referrals to PC is improved education for hematologists, the authors said, citing a study showing that 98% of oncology fellows at one center reported improvement in their ability to assess and manage patient symptoms after completion of a 4-week mandatory PC rotation.
“Another strategy to improve referrals to PC of hematologic malignancies patients could be the creation of programs which facilitate collaboration between PC providers and hematologists, such as the palliative and supportive care special interest group within the American Society for Transplantation and Cellular Therapy,” they wrote.
A third strategy “could be to provide a concurrent care model, in which cancer directed therapy (such as transfusions) is provided at the same time as hospice care,” they added, explaining that such an approach was shown in a study of patients with advanced non–small cell lung cancer to be associated with less aggressive medical treatment and lower costs.
The authors also stressed that patient with solid tumors and those with hematologic malignancies have differing supportive care needs and health care utilization, but several studies included in the current review included both types of cancer.
“Further studies investigating PC use exclusively in patients with hematologic malignancies are needed. Our results demonstrate a strong argument for hematologists to refer their patients early and often for specialized PC,” they concluded.
Indeed, when PC is integrated within hematologic malignancies, impacts occur that are similar to those seen in a variety of other diseases and include improved symptom control, enhanced caregiver experience, and reduced burdens on the health care system, Toby C Campbell, MD, said in an interview.
“The benefits of providing palliative care concurrent with standard cancer care is felt by all the major stakeholders in this care: the patients, their caregivers, and the health care system around them,” said Dr. Campbell, a thoracic medical oncologist and professor in the division of hematology, medical oncology, and palliative care at the University of Wisconsin–Madison.
Overcoming challenges
However, this is “new territory” for most programs, added Dr. Campbell, who also is the University of Wisconsin health chief of palliative care and holds the Ellen and Peter O. Johnson Chair in Palliative Care .
“The palliative care clinicians have a lot of learning to do if they’re going to enter this space and provide expert care,” he said, adding that expert care is what is needed and what was studied in this review. “Providing palliative care to patients with hematologic malignancies has a unique pace and a number of subspecialized therapeutic options with which the palliative care clinician must become familiar.”
Examples include bone marrow transplantation with prolonged hospitalizations and transfusion support, he said.
“Palliative care programs, in order to provide high quality care, will need to familiarize themselves with these therapies and develop close partnership with hematologists to integrate seamlessly into the patient’s care,” he added. “At some centers, culture changes will be necessary concurrent with the clinical practice change of integrating palliative care and it is the responsibility of the palliative care clinicians to bring their very best to these new relationships and patient populations.”
The authors reported having no disclosures. Dr. Campbell also reported having no disclosures.
Specialty palliative care interventions improve outcomes in patients with hematologic malignancies but are underutilized, according to findings from a systematic literature review.
Outcomes that were improved, as demonstrated by 16 studies that met inclusion criteria for the review, included symptom management, inpatient mortality, health care utilization, health care costs, and caregiver-reported outcomes, Elizabeth Elliott, DO, a hematology and oncology fellow at the Cardinal Bernardin Cancer Center, Loyola University, Maywood, Ill., and colleagues reported.
The findings were published online in the Journal of Pain and Symptom Management.
Palliative care needs
Patients with hematologic malignancies, including leukemia, myeloma, and lymphoma, have a high need for supportive care, the authors noted, adding that, although its use has increased over time, palliative care (PC) is often provided late in the disease course – sometimes only in the final days of life.
“Compared with their solid tumor counterparts, patients with hematologic malignancies experience higher symptom burdens, have higher rates of cancer-directed care near death, and are more likely to die while hospitalized than at home or in hospice,” they wrote. “Despite this need, specialist palliative care is less commonly utilized in patients with hematologic malignancies than other cancer types.”
Given the high health care utilization among patients with hematologic malignancies, earlier and more widespread utilization of PC in this population may significantly reduce health care costs, they added.
Palliative care benefits
Of 5,345 studies published between 2005 and 2020 and screened for the current review, 16 met inclusion criteria, including 10 retrospective cohort studies; 4 prospective cohort studies; and 2 randomized, controlled studies.
Nine studies included only patients with hematologic malignancies and seven included both patients with solid tumors and patients with hematologic malignancies. Each study assessed as being of moderate quality.
Benefits of PC as demonstrated in the studies included:
Symptom management: One study, for example, showed that an integrated psychological and PC intervention improved traumatic stress levels, degree and number of physical symptoms, pain intensity, depressive symptoms, and quality of life, compared with no intervention. Another showed that the percentage of patients reporting moderate to severe pain improved from 57% to 18% with a PC intervention, and the number reporting depressive episodes improved from 13% to 5%.
Reduced in-patient death: Findings from eight studies showed that 21.9%-83% of those receiving PC died at home, compared with 6.0%-8.9% of controls. Two studies showed that PC provided at least 20 days prior to death decreased the likelihood of inpatient death and death in an ICU, compared with controls, and one showed that the rate of in-hospital deaths was 30% for those with home PC or hospice, compared with 80% of controls.
Health care utilization: The studies showed that hospitalization occurred in 45%-76.3% of hematologic malignancy patients who received PC, compared with 98% of controls. The odds ratio for hospitalization among acute leukemia patients receiving PC was 0.64, compared with 2.53 among those in a historical control group.
Caregiver-reported outcomes: One randomized, controlled study showed that PC was associated with smaller increases in depression scores, improved coping, and improved scores in multiple quality of life domains in caregivers versus controls.
Survival: One study showed that a larger percentage of hematologic malignancy patients who died 1-6 months after diagnosis had not received PC (28% vs. 23%), whereas more of those who died 6-12 months or 12 or more months after diagnosis had received PC (23.9 vs. 14.9% and 42.5% vs. 22.0%).
Health care costs: Two studies showed a decrease in inpatient costs after a palliative care consultation. Decreases in hospitalization costs were $2,321 and $1,506 for less medically complex patients and $3,515 and $5,617 for more medically complex patient.
Improving PC utilization
One potential strategy to promote earlier referrals to PC is improved education for hematologists, the authors said, citing a study showing that 98% of oncology fellows at one center reported improvement in their ability to assess and manage patient symptoms after completion of a 4-week mandatory PC rotation.
“Another strategy to improve referrals to PC of hematologic malignancies patients could be the creation of programs which facilitate collaboration between PC providers and hematologists, such as the palliative and supportive care special interest group within the American Society for Transplantation and Cellular Therapy,” they wrote.
A third strategy “could be to provide a concurrent care model, in which cancer directed therapy (such as transfusions) is provided at the same time as hospice care,” they added, explaining that such an approach was shown in a study of patients with advanced non–small cell lung cancer to be associated with less aggressive medical treatment and lower costs.
The authors also stressed that patient with solid tumors and those with hematologic malignancies have differing supportive care needs and health care utilization, but several studies included in the current review included both types of cancer.
“Further studies investigating PC use exclusively in patients with hematologic malignancies are needed. Our results demonstrate a strong argument for hematologists to refer their patients early and often for specialized PC,” they concluded.
Indeed, when PC is integrated within hematologic malignancies, impacts occur that are similar to those seen in a variety of other diseases and include improved symptom control, enhanced caregiver experience, and reduced burdens on the health care system, Toby C Campbell, MD, said in an interview.
“The benefits of providing palliative care concurrent with standard cancer care is felt by all the major stakeholders in this care: the patients, their caregivers, and the health care system around them,” said Dr. Campbell, a thoracic medical oncologist and professor in the division of hematology, medical oncology, and palliative care at the University of Wisconsin–Madison.
Overcoming challenges
However, this is “new territory” for most programs, added Dr. Campbell, who also is the University of Wisconsin health chief of palliative care and holds the Ellen and Peter O. Johnson Chair in Palliative Care .
“The palliative care clinicians have a lot of learning to do if they’re going to enter this space and provide expert care,” he said, adding that expert care is what is needed and what was studied in this review. “Providing palliative care to patients with hematologic malignancies has a unique pace and a number of subspecialized therapeutic options with which the palliative care clinician must become familiar.”
Examples include bone marrow transplantation with prolonged hospitalizations and transfusion support, he said.
“Palliative care programs, in order to provide high quality care, will need to familiarize themselves with these therapies and develop close partnership with hematologists to integrate seamlessly into the patient’s care,” he added. “At some centers, culture changes will be necessary concurrent with the clinical practice change of integrating palliative care and it is the responsibility of the palliative care clinicians to bring their very best to these new relationships and patient populations.”
The authors reported having no disclosures. Dr. Campbell also reported having no disclosures.
Specialty palliative care interventions improve outcomes in patients with hematologic malignancies but are underutilized, according to findings from a systematic literature review.
Outcomes that were improved, as demonstrated by 16 studies that met inclusion criteria for the review, included symptom management, inpatient mortality, health care utilization, health care costs, and caregiver-reported outcomes, Elizabeth Elliott, DO, a hematology and oncology fellow at the Cardinal Bernardin Cancer Center, Loyola University, Maywood, Ill., and colleagues reported.
The findings were published online in the Journal of Pain and Symptom Management.
Palliative care needs
Patients with hematologic malignancies, including leukemia, myeloma, and lymphoma, have a high need for supportive care, the authors noted, adding that, although its use has increased over time, palliative care (PC) is often provided late in the disease course – sometimes only in the final days of life.
“Compared with their solid tumor counterparts, patients with hematologic malignancies experience higher symptom burdens, have higher rates of cancer-directed care near death, and are more likely to die while hospitalized than at home or in hospice,” they wrote. “Despite this need, specialist palliative care is less commonly utilized in patients with hematologic malignancies than other cancer types.”
Given the high health care utilization among patients with hematologic malignancies, earlier and more widespread utilization of PC in this population may significantly reduce health care costs, they added.
Palliative care benefits
Of 5,345 studies published between 2005 and 2020 and screened for the current review, 16 met inclusion criteria, including 10 retrospective cohort studies; 4 prospective cohort studies; and 2 randomized, controlled studies.
Nine studies included only patients with hematologic malignancies and seven included both patients with solid tumors and patients with hematologic malignancies. Each study assessed as being of moderate quality.
Benefits of PC as demonstrated in the studies included:
Symptom management: One study, for example, showed that an integrated psychological and PC intervention improved traumatic stress levels, degree and number of physical symptoms, pain intensity, depressive symptoms, and quality of life, compared with no intervention. Another showed that the percentage of patients reporting moderate to severe pain improved from 57% to 18% with a PC intervention, and the number reporting depressive episodes improved from 13% to 5%.
Reduced in-patient death: Findings from eight studies showed that 21.9%-83% of those receiving PC died at home, compared with 6.0%-8.9% of controls. Two studies showed that PC provided at least 20 days prior to death decreased the likelihood of inpatient death and death in an ICU, compared with controls, and one showed that the rate of in-hospital deaths was 30% for those with home PC or hospice, compared with 80% of controls.
Health care utilization: The studies showed that hospitalization occurred in 45%-76.3% of hematologic malignancy patients who received PC, compared with 98% of controls. The odds ratio for hospitalization among acute leukemia patients receiving PC was 0.64, compared with 2.53 among those in a historical control group.
Caregiver-reported outcomes: One randomized, controlled study showed that PC was associated with smaller increases in depression scores, improved coping, and improved scores in multiple quality of life domains in caregivers versus controls.
Survival: One study showed that a larger percentage of hematologic malignancy patients who died 1-6 months after diagnosis had not received PC (28% vs. 23%), whereas more of those who died 6-12 months or 12 or more months after diagnosis had received PC (23.9 vs. 14.9% and 42.5% vs. 22.0%).
Health care costs: Two studies showed a decrease in inpatient costs after a palliative care consultation. Decreases in hospitalization costs were $2,321 and $1,506 for less medically complex patients and $3,515 and $5,617 for more medically complex patient.
Improving PC utilization
One potential strategy to promote earlier referrals to PC is improved education for hematologists, the authors said, citing a study showing that 98% of oncology fellows at one center reported improvement in their ability to assess and manage patient symptoms after completion of a 4-week mandatory PC rotation.
“Another strategy to improve referrals to PC of hematologic malignancies patients could be the creation of programs which facilitate collaboration between PC providers and hematologists, such as the palliative and supportive care special interest group within the American Society for Transplantation and Cellular Therapy,” they wrote.
A third strategy “could be to provide a concurrent care model, in which cancer directed therapy (such as transfusions) is provided at the same time as hospice care,” they added, explaining that such an approach was shown in a study of patients with advanced non–small cell lung cancer to be associated with less aggressive medical treatment and lower costs.
The authors also stressed that patient with solid tumors and those with hematologic malignancies have differing supportive care needs and health care utilization, but several studies included in the current review included both types of cancer.
“Further studies investigating PC use exclusively in patients with hematologic malignancies are needed. Our results demonstrate a strong argument for hematologists to refer their patients early and often for specialized PC,” they concluded.
Indeed, when PC is integrated within hematologic malignancies, impacts occur that are similar to those seen in a variety of other diseases and include improved symptom control, enhanced caregiver experience, and reduced burdens on the health care system, Toby C Campbell, MD, said in an interview.
“The benefits of providing palliative care concurrent with standard cancer care is felt by all the major stakeholders in this care: the patients, their caregivers, and the health care system around them,” said Dr. Campbell, a thoracic medical oncologist and professor in the division of hematology, medical oncology, and palliative care at the University of Wisconsin–Madison.
Overcoming challenges
However, this is “new territory” for most programs, added Dr. Campbell, who also is the University of Wisconsin health chief of palliative care and holds the Ellen and Peter O. Johnson Chair in Palliative Care .
“The palliative care clinicians have a lot of learning to do if they’re going to enter this space and provide expert care,” he said, adding that expert care is what is needed and what was studied in this review. “Providing palliative care to patients with hematologic malignancies has a unique pace and a number of subspecialized therapeutic options with which the palliative care clinician must become familiar.”
Examples include bone marrow transplantation with prolonged hospitalizations and transfusion support, he said.
“Palliative care programs, in order to provide high quality care, will need to familiarize themselves with these therapies and develop close partnership with hematologists to integrate seamlessly into the patient’s care,” he added. “At some centers, culture changes will be necessary concurrent with the clinical practice change of integrating palliative care and it is the responsibility of the palliative care clinicians to bring their very best to these new relationships and patient populations.”
The authors reported having no disclosures. Dr. Campbell also reported having no disclosures.
FROM THE JOURNAL OF PAIN AND SYMPTOM MANAGEMENT
Cancer screening stopped by pandemic: Repercussions to come?
Last year, cancer screening programs around the world ground to a halt as SARS-CoV-2 infection rates surged globally. The effect of this slowdown is now becoming clear.
Thousands of cancer diagnoses are “missing,” and oncologists worry that this will lead to more advanced cancers and higher mortality for years to come.
“I feel like this is an earthquake that’s rocked our health care system. My guess is that you’ll probably still see repercussions of this over the next couple of years at least,” said Sharon Chang, MD, an attending surgical oncologist in the Permanente Medical Group, Fremont, Calif.
She was senior author of a study that analyzed the effects of the slowdown in mammography screening as a result of California’s “shelter-in-place” order on March 17, 2020. In the 2 months that followed, there were 64% fewer breast cancer diagnoses at 21 Kaiser Permanente medical centers, compared with the same period in 2019 (250 vs. 703).
In effect, approximately 450 breast cancer patients had “disappeared,” said coauthor Annie Tang, MD, a research fellow at the University of California, San Francisco, East Bay surgery program.
“What surprised me most from our data was the sheer number of breast cancer patients that were missing,” Dr. Tang said in an interview.
A similar picture has emerged elsewhere.
In Boston, an estimated 1,438 cancerous and precancerous lesions “went missing” during the first 3 months of pandemic shutdown, according to a study from the Massachusetts General Brigham health care system.
In this study, the investigators assessed screening rates for five cancers – breast cancer (mammography), prostate cancer (prostate-specific antigen testing), colorectal cancer (colonoscopy), cervical cancer (Papanicolaou tests), and lung cancer (low-dose CT).
Screening rates during the first peak of the pandemic (March 2 to June 2, 2020) were compared with those during the preceding and following 3 months and during the same 3 months in 2019.
The results showed a pronounced drop in screening rates during the peak pandemic period, compared with the three control periods. Decreases occurred for all screening tests and ranged from –60% to –82%.
There were also significant decreases in cancer diagnoses resulting from the decreases in screening tests, ranging from –19% to –78%.
“Quantifying the actual problem made us realize how much work needs to be done to get us back to prepandemic numbers,” said senior author Quoc-Dien Trinh, MD, FACS, codirector of the Dana Farber/Brigham and Women’s prostate cancer program.
In the Canadian province of Alberta, a similar decrease in cancer diagnoses occurred during the early days of the pandemic.
By the end of 2020, Alberta was “missing” approximately 2,000 cases of invasive cancers and 1,000 cases of noninvasive cancers, Doug Stewart, MD, senior medical director at the Cancer Strategic Clinical Network (SCN) of Alberta Health Services, told this news organization.
Dr. Stewart is able to track cancer diagnoses in Alberta almost in real time through a mandatory cancer registry. Within a month of shutdown, there was a 30% decrease in diagnoses of invasive cancers and a 50% decrease “in the kind of preinvasive cancers that, for the most part, are picked up by screening programs,” said Dr. Stewart.
After the health care system opened up again in the summer, Stewart said, noninvasive cancer diagnoses continued to be 20% lower than expected. There was a 10% shortfall in invasive cancer diagnoses.
The number of diagnoses had returned to normal by December 2020. However, Dr. Stewart is worried that this fact conceals a terrible truth.
The worry is over the backlog. Although the number of diagnoses is now similar to what it was before the pandemic, “people are presenting later, and maybe the cancer is more advanced,” he speculated.
His team at Alberta Health Services is assessing whether the cancers that are being diagnosed now are more advanced. Initial results are anticipated by late April 2021.
In the United Kingdom, there was a similar halt in cancer screening as a result of the country’s lockdown. Researchers now predict an uptick in cancer diagnoses.
Ajay Aggarwal, MD, PhD, consultant clinical oncologist and associate professor at the London School of Hygiene and Tropical Medicine, and colleagues have estimated that at least 3,500 deaths from breast, colorectal, esophageal, and lung cancer will occur during the next 5 years in England that could have been avoided had it not been for the lockdown measures necessitated by the pandemic.
Speaking to this news organization, Dr. Aggarwal warned that these numbers, which are from a modeling study published in August 2020, are “extremely conservative,” because the investigators considered diagnostic delays over only a 3-month period, the analysis involved only four cancers, and it did not reflect deferral of cancer treatment.
“It felt like it was the tip of the iceberg,” Dr. Aggarwal said. He warns that more recent data suggest that “diagnostic delays are probably worse than we predicted.”
He suspects that there is more at play than screening cancellations.
In another study conducted in the United Kingdom, data show “a falling edge of referrals” from primary care to cancer centers early in the pandemic. In that study, investigators analyzed real-time weekly hospital data from eight large British hospitals and found that urgent cancer referrals fell 70% at their lowest point.
“It really surprised me that the urgent referrals dropped so drastically,” said lead author Alvina Lai, PhD, a lecturer in health data analytics at University College London.
She attributed this in part to patients’ adherence to lockdown rules. “Patients are trying to follow government guidelines to stay home and not go to [general practitioners] unless necessary,” Dr. Lai explained in an interview.
Canada, like the United Kingdom, has a publicly funded health care system. Dr. Stewart came to a similar conclusion. “Some patients who have been diagnosed with cancer ... have told me it took them an extra couple of months to even contact the family doc, because they ... didn’t want to bother the family doctor with something that wasn’t COVID, this kind of guilt. They want to do something good for society. You know, most people are just really nice people, and they don’t want to bother the health care system if they don’t have COVID,” Dr. Stewart said.
Shelley Fuld Nasso, CEO of the National Coalition for Cancer Survivorship, a nonprofit organization based in Silver Spring, Md., agreed that screening shutdowns are not the only danger. “While we agree that screening is really important, we also want to make sure patients are following up with their physicians about symptoms that they have,” she said.
“Some of the speculation or concern about increased mortality for cancer is related to screening, but some of it is related to delayed diagnosis because of not following up on symptoms. ... What concerns me is not everyone has that ability or willingness to advocate for themselves,” she said.
Speaking at a press briefing held by the American Society for Radiation Oncology on March 30, Dr. Nasso related a case involving a patient who experienced severe arm pain. In a teleconsultation with her primary care physician, her condition was diagnosed as arthritis. She was subsequently diagnosed in the ED as having multiple myeloma.
Patients who “feel fine” may postpone their checkups to avoid going to the hospital and risking exposure to COVID-19.
“Some patients are still hesitant about returning for their mammograms or coming in if they feel a breast lump,” Dr. Tang said. “That fear of COVID-19 is still out there, and we don’t know how long patients are going to delay.”
In London, Dr. Aggarwal saw a similar response to the pandemic. “People were overestimating quite significantly what their risk of death was from acquiring COVID-19, and I think that balance was never [redressed] explicitly,” he said.
Public health initiatives to rebalance the messaging are now underway.
Public Health England and National Health Service England launched their Help Us Help You campaign in October 2020. The public information campaign urges people to speak to their doctors if they were “worried about a symptom that could be cancer.”
In Canada, the provincial government in Alberta has launched a public awareness campaign that conveys the message, “cancer has not gone away.”
“Cancer is still the No. 1 cause of potential life-years lost, despite COVID,” Dr. Stewart said. “We need to do what we can to make sure there’s no slippage in survival rates.”
Dr. Tang, Dr. Chang, Dr. Lai, Dr. Stewart, and Dr. Aggarwal have disclosed no relevant financial relationship. Dr. Trinh has received personal fees from Astellas, Bayer, and Janssen and grants from Intuitive Surgical.
A version of this article first appeared on Medscape.com.
Last year, cancer screening programs around the world ground to a halt as SARS-CoV-2 infection rates surged globally. The effect of this slowdown is now becoming clear.
Thousands of cancer diagnoses are “missing,” and oncologists worry that this will lead to more advanced cancers and higher mortality for years to come.
“I feel like this is an earthquake that’s rocked our health care system. My guess is that you’ll probably still see repercussions of this over the next couple of years at least,” said Sharon Chang, MD, an attending surgical oncologist in the Permanente Medical Group, Fremont, Calif.
She was senior author of a study that analyzed the effects of the slowdown in mammography screening as a result of California’s “shelter-in-place” order on March 17, 2020. In the 2 months that followed, there were 64% fewer breast cancer diagnoses at 21 Kaiser Permanente medical centers, compared with the same period in 2019 (250 vs. 703).
In effect, approximately 450 breast cancer patients had “disappeared,” said coauthor Annie Tang, MD, a research fellow at the University of California, San Francisco, East Bay surgery program.
“What surprised me most from our data was the sheer number of breast cancer patients that were missing,” Dr. Tang said in an interview.
A similar picture has emerged elsewhere.
In Boston, an estimated 1,438 cancerous and precancerous lesions “went missing” during the first 3 months of pandemic shutdown, according to a study from the Massachusetts General Brigham health care system.
In this study, the investigators assessed screening rates for five cancers – breast cancer (mammography), prostate cancer (prostate-specific antigen testing), colorectal cancer (colonoscopy), cervical cancer (Papanicolaou tests), and lung cancer (low-dose CT).
Screening rates during the first peak of the pandemic (March 2 to June 2, 2020) were compared with those during the preceding and following 3 months and during the same 3 months in 2019.
The results showed a pronounced drop in screening rates during the peak pandemic period, compared with the three control periods. Decreases occurred for all screening tests and ranged from –60% to –82%.
There were also significant decreases in cancer diagnoses resulting from the decreases in screening tests, ranging from –19% to –78%.
“Quantifying the actual problem made us realize how much work needs to be done to get us back to prepandemic numbers,” said senior author Quoc-Dien Trinh, MD, FACS, codirector of the Dana Farber/Brigham and Women’s prostate cancer program.
In the Canadian province of Alberta, a similar decrease in cancer diagnoses occurred during the early days of the pandemic.
By the end of 2020, Alberta was “missing” approximately 2,000 cases of invasive cancers and 1,000 cases of noninvasive cancers, Doug Stewart, MD, senior medical director at the Cancer Strategic Clinical Network (SCN) of Alberta Health Services, told this news organization.
Dr. Stewart is able to track cancer diagnoses in Alberta almost in real time through a mandatory cancer registry. Within a month of shutdown, there was a 30% decrease in diagnoses of invasive cancers and a 50% decrease “in the kind of preinvasive cancers that, for the most part, are picked up by screening programs,” said Dr. Stewart.
After the health care system opened up again in the summer, Stewart said, noninvasive cancer diagnoses continued to be 20% lower than expected. There was a 10% shortfall in invasive cancer diagnoses.
The number of diagnoses had returned to normal by December 2020. However, Dr. Stewart is worried that this fact conceals a terrible truth.
The worry is over the backlog. Although the number of diagnoses is now similar to what it was before the pandemic, “people are presenting later, and maybe the cancer is more advanced,” he speculated.
His team at Alberta Health Services is assessing whether the cancers that are being diagnosed now are more advanced. Initial results are anticipated by late April 2021.
In the United Kingdom, there was a similar halt in cancer screening as a result of the country’s lockdown. Researchers now predict an uptick in cancer diagnoses.
Ajay Aggarwal, MD, PhD, consultant clinical oncologist and associate professor at the London School of Hygiene and Tropical Medicine, and colleagues have estimated that at least 3,500 deaths from breast, colorectal, esophageal, and lung cancer will occur during the next 5 years in England that could have been avoided had it not been for the lockdown measures necessitated by the pandemic.
Speaking to this news organization, Dr. Aggarwal warned that these numbers, which are from a modeling study published in August 2020, are “extremely conservative,” because the investigators considered diagnostic delays over only a 3-month period, the analysis involved only four cancers, and it did not reflect deferral of cancer treatment.
“It felt like it was the tip of the iceberg,” Dr. Aggarwal said. He warns that more recent data suggest that “diagnostic delays are probably worse than we predicted.”
He suspects that there is more at play than screening cancellations.
In another study conducted in the United Kingdom, data show “a falling edge of referrals” from primary care to cancer centers early in the pandemic. In that study, investigators analyzed real-time weekly hospital data from eight large British hospitals and found that urgent cancer referrals fell 70% at their lowest point.
“It really surprised me that the urgent referrals dropped so drastically,” said lead author Alvina Lai, PhD, a lecturer in health data analytics at University College London.
She attributed this in part to patients’ adherence to lockdown rules. “Patients are trying to follow government guidelines to stay home and not go to [general practitioners] unless necessary,” Dr. Lai explained in an interview.
Canada, like the United Kingdom, has a publicly funded health care system. Dr. Stewart came to a similar conclusion. “Some patients who have been diagnosed with cancer ... have told me it took them an extra couple of months to even contact the family doc, because they ... didn’t want to bother the family doctor with something that wasn’t COVID, this kind of guilt. They want to do something good for society. You know, most people are just really nice people, and they don’t want to bother the health care system if they don’t have COVID,” Dr. Stewart said.
Shelley Fuld Nasso, CEO of the National Coalition for Cancer Survivorship, a nonprofit organization based in Silver Spring, Md., agreed that screening shutdowns are not the only danger. “While we agree that screening is really important, we also want to make sure patients are following up with their physicians about symptoms that they have,” she said.
“Some of the speculation or concern about increased mortality for cancer is related to screening, but some of it is related to delayed diagnosis because of not following up on symptoms. ... What concerns me is not everyone has that ability or willingness to advocate for themselves,” she said.
Speaking at a press briefing held by the American Society for Radiation Oncology on March 30, Dr. Nasso related a case involving a patient who experienced severe arm pain. In a teleconsultation with her primary care physician, her condition was diagnosed as arthritis. She was subsequently diagnosed in the ED as having multiple myeloma.
Patients who “feel fine” may postpone their checkups to avoid going to the hospital and risking exposure to COVID-19.
“Some patients are still hesitant about returning for their mammograms or coming in if they feel a breast lump,” Dr. Tang said. “That fear of COVID-19 is still out there, and we don’t know how long patients are going to delay.”
In London, Dr. Aggarwal saw a similar response to the pandemic. “People were overestimating quite significantly what their risk of death was from acquiring COVID-19, and I think that balance was never [redressed] explicitly,” he said.
Public health initiatives to rebalance the messaging are now underway.
Public Health England and National Health Service England launched their Help Us Help You campaign in October 2020. The public information campaign urges people to speak to their doctors if they were “worried about a symptom that could be cancer.”
In Canada, the provincial government in Alberta has launched a public awareness campaign that conveys the message, “cancer has not gone away.”
“Cancer is still the No. 1 cause of potential life-years lost, despite COVID,” Dr. Stewart said. “We need to do what we can to make sure there’s no slippage in survival rates.”
Dr. Tang, Dr. Chang, Dr. Lai, Dr. Stewart, and Dr. Aggarwal have disclosed no relevant financial relationship. Dr. Trinh has received personal fees from Astellas, Bayer, and Janssen and grants from Intuitive Surgical.
A version of this article first appeared on Medscape.com.
Last year, cancer screening programs around the world ground to a halt as SARS-CoV-2 infection rates surged globally. The effect of this slowdown is now becoming clear.
Thousands of cancer diagnoses are “missing,” and oncologists worry that this will lead to more advanced cancers and higher mortality for years to come.
“I feel like this is an earthquake that’s rocked our health care system. My guess is that you’ll probably still see repercussions of this over the next couple of years at least,” said Sharon Chang, MD, an attending surgical oncologist in the Permanente Medical Group, Fremont, Calif.
She was senior author of a study that analyzed the effects of the slowdown in mammography screening as a result of California’s “shelter-in-place” order on March 17, 2020. In the 2 months that followed, there were 64% fewer breast cancer diagnoses at 21 Kaiser Permanente medical centers, compared with the same period in 2019 (250 vs. 703).
In effect, approximately 450 breast cancer patients had “disappeared,” said coauthor Annie Tang, MD, a research fellow at the University of California, San Francisco, East Bay surgery program.
“What surprised me most from our data was the sheer number of breast cancer patients that were missing,” Dr. Tang said in an interview.
A similar picture has emerged elsewhere.
In Boston, an estimated 1,438 cancerous and precancerous lesions “went missing” during the first 3 months of pandemic shutdown, according to a study from the Massachusetts General Brigham health care system.
In this study, the investigators assessed screening rates for five cancers – breast cancer (mammography), prostate cancer (prostate-specific antigen testing), colorectal cancer (colonoscopy), cervical cancer (Papanicolaou tests), and lung cancer (low-dose CT).
Screening rates during the first peak of the pandemic (March 2 to June 2, 2020) were compared with those during the preceding and following 3 months and during the same 3 months in 2019.
The results showed a pronounced drop in screening rates during the peak pandemic period, compared with the three control periods. Decreases occurred for all screening tests and ranged from –60% to –82%.
There were also significant decreases in cancer diagnoses resulting from the decreases in screening tests, ranging from –19% to –78%.
“Quantifying the actual problem made us realize how much work needs to be done to get us back to prepandemic numbers,” said senior author Quoc-Dien Trinh, MD, FACS, codirector of the Dana Farber/Brigham and Women’s prostate cancer program.
In the Canadian province of Alberta, a similar decrease in cancer diagnoses occurred during the early days of the pandemic.
By the end of 2020, Alberta was “missing” approximately 2,000 cases of invasive cancers and 1,000 cases of noninvasive cancers, Doug Stewart, MD, senior medical director at the Cancer Strategic Clinical Network (SCN) of Alberta Health Services, told this news organization.
Dr. Stewart is able to track cancer diagnoses in Alberta almost in real time through a mandatory cancer registry. Within a month of shutdown, there was a 30% decrease in diagnoses of invasive cancers and a 50% decrease “in the kind of preinvasive cancers that, for the most part, are picked up by screening programs,” said Dr. Stewart.
After the health care system opened up again in the summer, Stewart said, noninvasive cancer diagnoses continued to be 20% lower than expected. There was a 10% shortfall in invasive cancer diagnoses.
The number of diagnoses had returned to normal by December 2020. However, Dr. Stewart is worried that this fact conceals a terrible truth.
The worry is over the backlog. Although the number of diagnoses is now similar to what it was before the pandemic, “people are presenting later, and maybe the cancer is more advanced,” he speculated.
His team at Alberta Health Services is assessing whether the cancers that are being diagnosed now are more advanced. Initial results are anticipated by late April 2021.
In the United Kingdom, there was a similar halt in cancer screening as a result of the country’s lockdown. Researchers now predict an uptick in cancer diagnoses.
Ajay Aggarwal, MD, PhD, consultant clinical oncologist and associate professor at the London School of Hygiene and Tropical Medicine, and colleagues have estimated that at least 3,500 deaths from breast, colorectal, esophageal, and lung cancer will occur during the next 5 years in England that could have been avoided had it not been for the lockdown measures necessitated by the pandemic.
Speaking to this news organization, Dr. Aggarwal warned that these numbers, which are from a modeling study published in August 2020, are “extremely conservative,” because the investigators considered diagnostic delays over only a 3-month period, the analysis involved only four cancers, and it did not reflect deferral of cancer treatment.
“It felt like it was the tip of the iceberg,” Dr. Aggarwal said. He warns that more recent data suggest that “diagnostic delays are probably worse than we predicted.”
He suspects that there is more at play than screening cancellations.
In another study conducted in the United Kingdom, data show “a falling edge of referrals” from primary care to cancer centers early in the pandemic. In that study, investigators analyzed real-time weekly hospital data from eight large British hospitals and found that urgent cancer referrals fell 70% at their lowest point.
“It really surprised me that the urgent referrals dropped so drastically,” said lead author Alvina Lai, PhD, a lecturer in health data analytics at University College London.
She attributed this in part to patients’ adherence to lockdown rules. “Patients are trying to follow government guidelines to stay home and not go to [general practitioners] unless necessary,” Dr. Lai explained in an interview.
Canada, like the United Kingdom, has a publicly funded health care system. Dr. Stewart came to a similar conclusion. “Some patients who have been diagnosed with cancer ... have told me it took them an extra couple of months to even contact the family doc, because they ... didn’t want to bother the family doctor with something that wasn’t COVID, this kind of guilt. They want to do something good for society. You know, most people are just really nice people, and they don’t want to bother the health care system if they don’t have COVID,” Dr. Stewart said.
Shelley Fuld Nasso, CEO of the National Coalition for Cancer Survivorship, a nonprofit organization based in Silver Spring, Md., agreed that screening shutdowns are not the only danger. “While we agree that screening is really important, we also want to make sure patients are following up with their physicians about symptoms that they have,” she said.
“Some of the speculation or concern about increased mortality for cancer is related to screening, but some of it is related to delayed diagnosis because of not following up on symptoms. ... What concerns me is not everyone has that ability or willingness to advocate for themselves,” she said.
Speaking at a press briefing held by the American Society for Radiation Oncology on March 30, Dr. Nasso related a case involving a patient who experienced severe arm pain. In a teleconsultation with her primary care physician, her condition was diagnosed as arthritis. She was subsequently diagnosed in the ED as having multiple myeloma.
Patients who “feel fine” may postpone their checkups to avoid going to the hospital and risking exposure to COVID-19.
“Some patients are still hesitant about returning for their mammograms or coming in if they feel a breast lump,” Dr. Tang said. “That fear of COVID-19 is still out there, and we don’t know how long patients are going to delay.”
In London, Dr. Aggarwal saw a similar response to the pandemic. “People were overestimating quite significantly what their risk of death was from acquiring COVID-19, and I think that balance was never [redressed] explicitly,” he said.
Public health initiatives to rebalance the messaging are now underway.
Public Health England and National Health Service England launched their Help Us Help You campaign in October 2020. The public information campaign urges people to speak to their doctors if they were “worried about a symptom that could be cancer.”
In Canada, the provincial government in Alberta has launched a public awareness campaign that conveys the message, “cancer has not gone away.”
“Cancer is still the No. 1 cause of potential life-years lost, despite COVID,” Dr. Stewart said. “We need to do what we can to make sure there’s no slippage in survival rates.”
Dr. Tang, Dr. Chang, Dr. Lai, Dr. Stewart, and Dr. Aggarwal have disclosed no relevant financial relationship. Dr. Trinh has received personal fees from Astellas, Bayer, and Janssen and grants from Intuitive Surgical.
A version of this article first appeared on Medscape.com.
New guidelines on antibiotic prescribing focus on shorter courses
An antibiotic course of 5 days is usually just as effective as longer courses but with fewer side effects and decreased overall antibiotic exposure for a number of common bacterial conditions, according to new clinical guidelines published by the American College of Physicians.
The guidelines focus on treatment of uncomplicated cases involving pneumonia, urinary tract infections (UTIs), cellulitis, chronic obstructive pulmonary disease (COPD) exacerbations, and acute bronchitis. The goal of the guidelines is to continue improving antibiotic stewardship given the increasing threat of antibiotic resistance and the adverse effects of antibiotics.
“Any use of antibiotics (including necessary use) has downstream effects outside of treating infection,” Dawn Nolt, MD, MPH, a professor of pediatric infection disease at Oregon Health & Science University, Portland, said in an interview. Dr. Nolt was not involved in developing these guidelines. “Undesirable outcomes include allergic reactions, diarrhea, and antibiotic-resistant bacteria. When we reduce unnecessary antibiotic, we reduce undesirable outcomes,” she said.
According to background information in the paper, 1 in 10 patients receives an antibiotic prescription during visits, yet nearly a third of these (30%) are unnecessary and last too long, especially for sinusitis and bronchitis. Meanwhile, overuse of antibiotics, particularly broad-spectrum ones, leads to resistance and adverse effects in up to 20% of patients.
“Prescribing practices can vary based on the type of provider, the setting where the antibiotic is being prescribed, what geographic area you are looking at, the medical reason for which the antibiotic is being prescribed, the actual germ being targeted, and the type of patient,” Dr. Nolt said. “But this variability can be reduced when prescribing providers are aware and follow best practice standards as through this article.”
The new ACP guidelines are a distillation of recommendations from preexisting infectious disease organizations, Dr. Nolt said, but aimed specifically at those practicing internal medicine.
“We define appropriate antibiotic use as prescribing the right antibiotic at the right dose for the right duration for a specific condition,” Rachael A. Lee, MD, MSPH, of the University of Alabama at Birmingham, and colleagues wrote in the article detailing the new guidelines. “Despite evidence and guidelines supporting shorter durations of antibiotic use, many physicians do not prescribe short-course therapy, frequently defaulting to 10-day courses regardless of the condition.”
The reasons for this default response vary. Though some clinicians prescribe longer courses specifically to prevent antibiotic resistance, no evidence shows that continuing to take antibiotics after symptoms have resolved actually reduces likelihood of resistance, the authors noted.
“In fact, resistance is a documented side effect of prolonged antibiotic use due to natural selection pressure,” they wrote.
Another common reason is habit.
“This was the ‘conventional wisdom’ for so long, just trying to make sure all bacteria causing the infection were completely eradicated, with no stragglers that had been exposed to the antibiotic but were not gone and now could evolve into resistant organisms,” Jacqueline W. Fincher, MD, a primary care physician and president of the ACP, said in an interview. “While antibiotic stewardship has been very important for over a decade, we now have more recent head-to-head studies/data showing that, in these four conditions, shorter courses of treatment are just as efficacious with less side effects and adverse events.”
The researchers reviewed all existing clinical guidelines related to bronchitis with COPD exacerbations, community-acquired pneumonia, UTIs, and cellulitis, as well as any other relevant studies in the literature. Although they did not conduct a formal systematic review, they compiled the guidelines specifically for all internists, family physicians and other clinicians caring for patients with these conditions.
“Although most patients with these infections will be seen in the outpatient setting, these best-practice advice statements also apply to patients who present in the inpatient setting,” the authors wrote. They also note the importance of ensuring the patient has the correct diagnosis and appropriate corresponding antibiotic prescription. “If a patient is not improving with appropriate antibiotics, it is important for the clinician to reassess for other causes of symptoms rather than defaulting to a longer duration of antibiotic therapy,” they wrote, calling a longer course “the exception and not the rule.”
Acute bronchitis with COPD exacerbations
Antibiotic treatment for COPD exacerbations and acute uncomplicated bronchitis with signs of a bacterial infection should last no longer than 5 days. The authors define this condition as an acute respiratory infection with a normal chest x-ray, most often caused by a virus. Although patients with bronchitis do not automatically need antibiotics if there’s no evidence of pneumonia, the authors did advise antibiotics in cases involving COPD and a high likelihood of bacterial infection. Clinicians should base their choice of antibiotics on the most common bacterial etiology: Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Ideal candidates for therapy may include aminopenicillin with clavulanic acid, a macrolide, or a tetracycline.
Community-acquired pneumonia
The initial course of antibiotics should be at least 5 days for pneumonia and only extended after considering validated evidence of the patient’s clinical stability, such as resuming normal vital signs, mental activity, and the ability to eat. Multiple randomized, controlled trials have shown no improved benefit from longer courses, though longer courses are linked to increased adverse events and mortality.
Again, antibiotics used should “cover common pathogens, such as S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, and Staphylococcus aureus, and atypical pathogens, such as Legionella species,” the authors wrote. Options include “amoxicillin, doxycycline, or a macrolide for healthy adults or a beta-lactam with a macrolide or a respiratory fluoroquinolone in patients with comorbidities.”
UTIs: Uncomplicated cystitis and pyelonephritis
For women’s bacterial cystitis – 75% of which is caused by Escherichia coli – the guidelines recommend nitrofurantoin for 5 days, trimethoprim-sulfamethoxazole for 3 days, or fosfomycin as a single dose. For uncomplicated pyelonephritis in both men and women, clinicians can consider fluoroquinolones for 5-7 days or trimethoprim-sulfamethoxazole for 14 days, depending on antibiotic susceptibility.
This recommendation does not include UTIs in women who are pregnant or UTIs with other functional abnormalities present, such as obstruction. The authors also intentionally left out acute bacterial prostatitis because of its complexity and how long it can take to treat.
Cellulitis
MRSA, which has been increasing in prevalence, is a leading cause of skin and soft-tissue infections, such as necrotizing infections, cellulitis, and erysipelas. Unless the patient has penetrating trauma, evidence of MRSA infection elsewhere, injection drug use, nasal colonization of MRSA, or systemic inflammatory response syndrome, the guidelines recommend a 5- to 6-day course of cephalosporin, penicillin, or clindamycin, extended only if the infection has not improved in 5 days. Further research can narrow down the most appropriate treatment course.
This guidance does not apply to purulent cellulitis, such as conditions with abscesses, furuncles, or carbuncles that typically require incision and drainage.
Continuing to get the message out
Dr. Fincher emphasized the importance of continuing to disseminate messaging for clinicians about reducing unnecessary antibiotic use.
“In medicine we are constantly bombarded with new information. It is those patients and disease states that we see and treat every day that are especially important for us as physicians and other clinicians to keep our skills and knowledge base up to date when it comes to use of antibiotics,” Dr. Fincher said in an interview. “We just need to continue to educate and push out the data, guidelines, and recommendations.”
Dr. Nolt added that it’s important to emphasize how to translate these national recommendations into local practices since local guidance can also raise awareness and encourage local compliance.
Other strategies for reducing overuse of antibiotics “include restriction on antibiotics available at health care systems (formulary restriction), not allowing use of antibiotics unless there is discussion about the patient’s case (preauthorization), and reviewing cases of patients on antibiotics and advising on next steps (prospective audit and feedback),” she said.
The research was funded by the ACP. Dr. Lee has received personal fees from this news organization and Prime Education. Dr. Fincher owns stock in Johnson & Johnson and Procter and Gamble. Dr. Nolt and the article’s coauthors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
An antibiotic course of 5 days is usually just as effective as longer courses but with fewer side effects and decreased overall antibiotic exposure for a number of common bacterial conditions, according to new clinical guidelines published by the American College of Physicians.
The guidelines focus on treatment of uncomplicated cases involving pneumonia, urinary tract infections (UTIs), cellulitis, chronic obstructive pulmonary disease (COPD) exacerbations, and acute bronchitis. The goal of the guidelines is to continue improving antibiotic stewardship given the increasing threat of antibiotic resistance and the adverse effects of antibiotics.
“Any use of antibiotics (including necessary use) has downstream effects outside of treating infection,” Dawn Nolt, MD, MPH, a professor of pediatric infection disease at Oregon Health & Science University, Portland, said in an interview. Dr. Nolt was not involved in developing these guidelines. “Undesirable outcomes include allergic reactions, diarrhea, and antibiotic-resistant bacteria. When we reduce unnecessary antibiotic, we reduce undesirable outcomes,” she said.
According to background information in the paper, 1 in 10 patients receives an antibiotic prescription during visits, yet nearly a third of these (30%) are unnecessary and last too long, especially for sinusitis and bronchitis. Meanwhile, overuse of antibiotics, particularly broad-spectrum ones, leads to resistance and adverse effects in up to 20% of patients.
“Prescribing practices can vary based on the type of provider, the setting where the antibiotic is being prescribed, what geographic area you are looking at, the medical reason for which the antibiotic is being prescribed, the actual germ being targeted, and the type of patient,” Dr. Nolt said. “But this variability can be reduced when prescribing providers are aware and follow best practice standards as through this article.”
The new ACP guidelines are a distillation of recommendations from preexisting infectious disease organizations, Dr. Nolt said, but aimed specifically at those practicing internal medicine.
“We define appropriate antibiotic use as prescribing the right antibiotic at the right dose for the right duration for a specific condition,” Rachael A. Lee, MD, MSPH, of the University of Alabama at Birmingham, and colleagues wrote in the article detailing the new guidelines. “Despite evidence and guidelines supporting shorter durations of antibiotic use, many physicians do not prescribe short-course therapy, frequently defaulting to 10-day courses regardless of the condition.”
The reasons for this default response vary. Though some clinicians prescribe longer courses specifically to prevent antibiotic resistance, no evidence shows that continuing to take antibiotics after symptoms have resolved actually reduces likelihood of resistance, the authors noted.
“In fact, resistance is a documented side effect of prolonged antibiotic use due to natural selection pressure,” they wrote.
Another common reason is habit.
“This was the ‘conventional wisdom’ for so long, just trying to make sure all bacteria causing the infection were completely eradicated, with no stragglers that had been exposed to the antibiotic but were not gone and now could evolve into resistant organisms,” Jacqueline W. Fincher, MD, a primary care physician and president of the ACP, said in an interview. “While antibiotic stewardship has been very important for over a decade, we now have more recent head-to-head studies/data showing that, in these four conditions, shorter courses of treatment are just as efficacious with less side effects and adverse events.”
The researchers reviewed all existing clinical guidelines related to bronchitis with COPD exacerbations, community-acquired pneumonia, UTIs, and cellulitis, as well as any other relevant studies in the literature. Although they did not conduct a formal systematic review, they compiled the guidelines specifically for all internists, family physicians and other clinicians caring for patients with these conditions.
“Although most patients with these infections will be seen in the outpatient setting, these best-practice advice statements also apply to patients who present in the inpatient setting,” the authors wrote. They also note the importance of ensuring the patient has the correct diagnosis and appropriate corresponding antibiotic prescription. “If a patient is not improving with appropriate antibiotics, it is important for the clinician to reassess for other causes of symptoms rather than defaulting to a longer duration of antibiotic therapy,” they wrote, calling a longer course “the exception and not the rule.”
Acute bronchitis with COPD exacerbations
Antibiotic treatment for COPD exacerbations and acute uncomplicated bronchitis with signs of a bacterial infection should last no longer than 5 days. The authors define this condition as an acute respiratory infection with a normal chest x-ray, most often caused by a virus. Although patients with bronchitis do not automatically need antibiotics if there’s no evidence of pneumonia, the authors did advise antibiotics in cases involving COPD and a high likelihood of bacterial infection. Clinicians should base their choice of antibiotics on the most common bacterial etiology: Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Ideal candidates for therapy may include aminopenicillin with clavulanic acid, a macrolide, or a tetracycline.
Community-acquired pneumonia
The initial course of antibiotics should be at least 5 days for pneumonia and only extended after considering validated evidence of the patient’s clinical stability, such as resuming normal vital signs, mental activity, and the ability to eat. Multiple randomized, controlled trials have shown no improved benefit from longer courses, though longer courses are linked to increased adverse events and mortality.
Again, antibiotics used should “cover common pathogens, such as S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, and Staphylococcus aureus, and atypical pathogens, such as Legionella species,” the authors wrote. Options include “amoxicillin, doxycycline, or a macrolide for healthy adults or a beta-lactam with a macrolide or a respiratory fluoroquinolone in patients with comorbidities.”
UTIs: Uncomplicated cystitis and pyelonephritis
For women’s bacterial cystitis – 75% of which is caused by Escherichia coli – the guidelines recommend nitrofurantoin for 5 days, trimethoprim-sulfamethoxazole for 3 days, or fosfomycin as a single dose. For uncomplicated pyelonephritis in both men and women, clinicians can consider fluoroquinolones for 5-7 days or trimethoprim-sulfamethoxazole for 14 days, depending on antibiotic susceptibility.
This recommendation does not include UTIs in women who are pregnant or UTIs with other functional abnormalities present, such as obstruction. The authors also intentionally left out acute bacterial prostatitis because of its complexity and how long it can take to treat.
Cellulitis
MRSA, which has been increasing in prevalence, is a leading cause of skin and soft-tissue infections, such as necrotizing infections, cellulitis, and erysipelas. Unless the patient has penetrating trauma, evidence of MRSA infection elsewhere, injection drug use, nasal colonization of MRSA, or systemic inflammatory response syndrome, the guidelines recommend a 5- to 6-day course of cephalosporin, penicillin, or clindamycin, extended only if the infection has not improved in 5 days. Further research can narrow down the most appropriate treatment course.
This guidance does not apply to purulent cellulitis, such as conditions with abscesses, furuncles, or carbuncles that typically require incision and drainage.
Continuing to get the message out
Dr. Fincher emphasized the importance of continuing to disseminate messaging for clinicians about reducing unnecessary antibiotic use.
“In medicine we are constantly bombarded with new information. It is those patients and disease states that we see and treat every day that are especially important for us as physicians and other clinicians to keep our skills and knowledge base up to date when it comes to use of antibiotics,” Dr. Fincher said in an interview. “We just need to continue to educate and push out the data, guidelines, and recommendations.”
Dr. Nolt added that it’s important to emphasize how to translate these national recommendations into local practices since local guidance can also raise awareness and encourage local compliance.
Other strategies for reducing overuse of antibiotics “include restriction on antibiotics available at health care systems (formulary restriction), not allowing use of antibiotics unless there is discussion about the patient’s case (preauthorization), and reviewing cases of patients on antibiotics and advising on next steps (prospective audit and feedback),” she said.
The research was funded by the ACP. Dr. Lee has received personal fees from this news organization and Prime Education. Dr. Fincher owns stock in Johnson & Johnson and Procter and Gamble. Dr. Nolt and the article’s coauthors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
An antibiotic course of 5 days is usually just as effective as longer courses but with fewer side effects and decreased overall antibiotic exposure for a number of common bacterial conditions, according to new clinical guidelines published by the American College of Physicians.
The guidelines focus on treatment of uncomplicated cases involving pneumonia, urinary tract infections (UTIs), cellulitis, chronic obstructive pulmonary disease (COPD) exacerbations, and acute bronchitis. The goal of the guidelines is to continue improving antibiotic stewardship given the increasing threat of antibiotic resistance and the adverse effects of antibiotics.
“Any use of antibiotics (including necessary use) has downstream effects outside of treating infection,” Dawn Nolt, MD, MPH, a professor of pediatric infection disease at Oregon Health & Science University, Portland, said in an interview. Dr. Nolt was not involved in developing these guidelines. “Undesirable outcomes include allergic reactions, diarrhea, and antibiotic-resistant bacteria. When we reduce unnecessary antibiotic, we reduce undesirable outcomes,” she said.
According to background information in the paper, 1 in 10 patients receives an antibiotic prescription during visits, yet nearly a third of these (30%) are unnecessary and last too long, especially for sinusitis and bronchitis. Meanwhile, overuse of antibiotics, particularly broad-spectrum ones, leads to resistance and adverse effects in up to 20% of patients.
“Prescribing practices can vary based on the type of provider, the setting where the antibiotic is being prescribed, what geographic area you are looking at, the medical reason for which the antibiotic is being prescribed, the actual germ being targeted, and the type of patient,” Dr. Nolt said. “But this variability can be reduced when prescribing providers are aware and follow best practice standards as through this article.”
The new ACP guidelines are a distillation of recommendations from preexisting infectious disease organizations, Dr. Nolt said, but aimed specifically at those practicing internal medicine.
“We define appropriate antibiotic use as prescribing the right antibiotic at the right dose for the right duration for a specific condition,” Rachael A. Lee, MD, MSPH, of the University of Alabama at Birmingham, and colleagues wrote in the article detailing the new guidelines. “Despite evidence and guidelines supporting shorter durations of antibiotic use, many physicians do not prescribe short-course therapy, frequently defaulting to 10-day courses regardless of the condition.”
The reasons for this default response vary. Though some clinicians prescribe longer courses specifically to prevent antibiotic resistance, no evidence shows that continuing to take antibiotics after symptoms have resolved actually reduces likelihood of resistance, the authors noted.
“In fact, resistance is a documented side effect of prolonged antibiotic use due to natural selection pressure,” they wrote.
Another common reason is habit.
“This was the ‘conventional wisdom’ for so long, just trying to make sure all bacteria causing the infection were completely eradicated, with no stragglers that had been exposed to the antibiotic but were not gone and now could evolve into resistant organisms,” Jacqueline W. Fincher, MD, a primary care physician and president of the ACP, said in an interview. “While antibiotic stewardship has been very important for over a decade, we now have more recent head-to-head studies/data showing that, in these four conditions, shorter courses of treatment are just as efficacious with less side effects and adverse events.”
The researchers reviewed all existing clinical guidelines related to bronchitis with COPD exacerbations, community-acquired pneumonia, UTIs, and cellulitis, as well as any other relevant studies in the literature. Although they did not conduct a formal systematic review, they compiled the guidelines specifically for all internists, family physicians and other clinicians caring for patients with these conditions.
“Although most patients with these infections will be seen in the outpatient setting, these best-practice advice statements also apply to patients who present in the inpatient setting,” the authors wrote. They also note the importance of ensuring the patient has the correct diagnosis and appropriate corresponding antibiotic prescription. “If a patient is not improving with appropriate antibiotics, it is important for the clinician to reassess for other causes of symptoms rather than defaulting to a longer duration of antibiotic therapy,” they wrote, calling a longer course “the exception and not the rule.”
Acute bronchitis with COPD exacerbations
Antibiotic treatment for COPD exacerbations and acute uncomplicated bronchitis with signs of a bacterial infection should last no longer than 5 days. The authors define this condition as an acute respiratory infection with a normal chest x-ray, most often caused by a virus. Although patients with bronchitis do not automatically need antibiotics if there’s no evidence of pneumonia, the authors did advise antibiotics in cases involving COPD and a high likelihood of bacterial infection. Clinicians should base their choice of antibiotics on the most common bacterial etiology: Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Ideal candidates for therapy may include aminopenicillin with clavulanic acid, a macrolide, or a tetracycline.
Community-acquired pneumonia
The initial course of antibiotics should be at least 5 days for pneumonia and only extended after considering validated evidence of the patient’s clinical stability, such as resuming normal vital signs, mental activity, and the ability to eat. Multiple randomized, controlled trials have shown no improved benefit from longer courses, though longer courses are linked to increased adverse events and mortality.
Again, antibiotics used should “cover common pathogens, such as S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, and Staphylococcus aureus, and atypical pathogens, such as Legionella species,” the authors wrote. Options include “amoxicillin, doxycycline, or a macrolide for healthy adults or a beta-lactam with a macrolide or a respiratory fluoroquinolone in patients with comorbidities.”
UTIs: Uncomplicated cystitis and pyelonephritis
For women’s bacterial cystitis – 75% of which is caused by Escherichia coli – the guidelines recommend nitrofurantoin for 5 days, trimethoprim-sulfamethoxazole for 3 days, or fosfomycin as a single dose. For uncomplicated pyelonephritis in both men and women, clinicians can consider fluoroquinolones for 5-7 days or trimethoprim-sulfamethoxazole for 14 days, depending on antibiotic susceptibility.
This recommendation does not include UTIs in women who are pregnant or UTIs with other functional abnormalities present, such as obstruction. The authors also intentionally left out acute bacterial prostatitis because of its complexity and how long it can take to treat.
Cellulitis
MRSA, which has been increasing in prevalence, is a leading cause of skin and soft-tissue infections, such as necrotizing infections, cellulitis, and erysipelas. Unless the patient has penetrating trauma, evidence of MRSA infection elsewhere, injection drug use, nasal colonization of MRSA, or systemic inflammatory response syndrome, the guidelines recommend a 5- to 6-day course of cephalosporin, penicillin, or clindamycin, extended only if the infection has not improved in 5 days. Further research can narrow down the most appropriate treatment course.
This guidance does not apply to purulent cellulitis, such as conditions with abscesses, furuncles, or carbuncles that typically require incision and drainage.
Continuing to get the message out
Dr. Fincher emphasized the importance of continuing to disseminate messaging for clinicians about reducing unnecessary antibiotic use.
“In medicine we are constantly bombarded with new information. It is those patients and disease states that we see and treat every day that are especially important for us as physicians and other clinicians to keep our skills and knowledge base up to date when it comes to use of antibiotics,” Dr. Fincher said in an interview. “We just need to continue to educate and push out the data, guidelines, and recommendations.”
Dr. Nolt added that it’s important to emphasize how to translate these national recommendations into local practices since local guidance can also raise awareness and encourage local compliance.
Other strategies for reducing overuse of antibiotics “include restriction on antibiotics available at health care systems (formulary restriction), not allowing use of antibiotics unless there is discussion about the patient’s case (preauthorization), and reviewing cases of patients on antibiotics and advising on next steps (prospective audit and feedback),” she said.
The research was funded by the ACP. Dr. Lee has received personal fees from this news organization and Prime Education. Dr. Fincher owns stock in Johnson & Johnson and Procter and Gamble. Dr. Nolt and the article’s coauthors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Starting April 5, patients can read your notes: 5 things to consider
Change in writing style is not mandated
The mandate, called “open notes” by many, is part of the 21st Century Cures Act, a wide-ranging piece of federal health care legislation. The previous deadline of Nov. 2, 2020, for enacting open notes was extended last year because of the exigencies of the COVID-19 pandemic.
Organizations must provide access via patient portals to the following types of notes: consultations, discharge summaries, histories, physical examination findings, imaging narratives, laboratory and pathology report narratives, and procedure and progress notes. Noncompliant organizations will eventually be subject to fines from the Department of Health & Human Services for “information blocking.”
This news organization reported on the mandate in 2020, and some readers said it was an unwelcome intrusion into practice. Since then, this news organization has run additional open notes stories about physician concerns, a perspective essay addressing those fears, and a reader poll about the phenomenon.
Now, as the legislation turns into a practical clinical matter, there are five key points clinicians should consider.
Clinicians don’t have to change writing style.
The new law mandates timely patient access to notes and test results, but it doesn’t require that clinicians alter their writing, said Scott MacDonald, MD, an internist and electronic health record medical director at University of California Davis Health in Sacramento.
“You don’t have to change your notes,” he said. However, patients are now part of the note audience and some health care systems are directing clinicians to make patient-friendly style changes.
Everyday experience should guide clinicians when writing notes, said one expert.
“When you’re not sure [of how to write a note], just mirror the way you would speak in the office – that’s going to get you right, including for mental health issues,” advised Leonor Fernandez, MD, an internist at Beth Deaconess Israel Medical Center, Boston, in her “take-away” comments in the online video, How to Write an Open Note.
According to a 2020 Medscape poll of 1,050 physicians, a majority (56%) anticipate that they will write notes differently, knowing that patients can read them via open notes. Nearly two-thirds (64%) believe that this new wrinkle in medical records will increase their workload. However, actual practice suggests that this is true for a minority of practitioners, according to the results from a recent study of more than 1,000 physicians in Boston, Seattle, and rural Pennsylvania, who already work in open notes settings. Only about one-third (37%) reported “spending more time on documentation.”
Note writing is going to change because of the addition of the patient reader, and something will be lost, argued Steven Reidbord, MD, a psychiatrist in private practice in San Francisco. By watering down the language for patients, “you are trading away the technical precision and other advantages of having a professional language,” commented Dr. Reidbord, who blogs for Psychology Today and has criticized the open notes movement in the past.
However, years of investigation from OpenNotes, the Boston-based advocacy and research organization, indicates that there are many gains with patient-accessible notes, including improved medical record accuracy, greater medication adherence, and potentially improved health care disparities among a range of patient types. In a 2019 study, researchers said that worry and confusion among note-reading patients are uncommon (5% and 3%, respectively), which addresses two criticisms voiced by multiple people last year.
Some clinical notes can be withheld.
The new rules from the federal government permit information blocking if there is clear evidence that doing so “will substantially reduce the risk of harm” to patients or to other third parties, Tom Delbanco, MD, and Charlotte Blease, PhD, of OpenNotes in Boston wrote in a commentary in February 2021.
There are also state-level laws that can supersede the new U.S. law and block access to notes, points out MacDonald. For example, California law dictates that providers cannot post cancer test results without talking with the patient first.
The OpenNotes organization also points out that, with regard to sensitive psychotherapy notes that are separated from the rest of a medical record, those notes “can be kept from patients without their permission, and such rules vary state by state.”
Some patients are more likely readers.
Some patients are more likely to peer into their files than others, said Liz Salmi, senior strategist at OpenNotes, who is also a brain cancer patient.
“Those patients who have more serious or chronic conditions ... are more likely to read their notes,” she said in an interview.
A new study of nearly 6,000 medical oncology patients at the University of Wisconsin confirmed that opinion. Patients with incurable metastatic disease were much more likely than those with early-stage, curable disease to read notes. Notably, younger patients were more likely than older ones to access notes, likely the result of generational tech savvy.
Despite the unpredictability of serious disease such as cancer, oncology patients find satisfaction in reading their notes, say experts. “We’ve overwhelmingly heard that patients like it,” Thomas LeBlanc, MD, medical oncologist at Duke University, Durham, N.C., where all patients already have access to clinicians’ notes, told this news organization in 2018.
You are part of the avant garde.
The United States and Scandinavian countries are the world leaders in implementing open notes in clinical practice, Dr. Blease said in an interview.
“It’s a phenomenal achievement” to have enacted open notes nationally, she said. For example, there are no open notes in Northern Ireland, Dr. Blease’s home country, or most of Europe.
In the United States, there are more than 200 medical organizations, including at least one in every state, that were voluntarily providing open notes before April 5, including interstate giants such as Banner Health and big-name medical centers such as Cleveland Clinic.
It may be hard for the United States to top Sweden’s embrace of the practice. The national open notes program now has 7.2 million patient accounts in a country of 10 million people, noted Maria Häggland, PhD, of Uppsala (Sweden) MedTech Science Innovation Center during a webinar last year.
The start day will come, and you may not notice.
“When April 5 happens, something brand new is going to happen symbolically,” Ms. Salmi said. Its importance is hard to measure.
“Patients say they trust their doctor more because they understand their thinking with open notes. How do you value that? We don’t have metrics for that,” she said.
Dr. MacDonald suggested that open notes are both new and not new. In the fall of 2020, he predicted that the launch day would come, and few clinicians would notice, in part because many patients already access truncated information via patient portals.
However, there are “sensitive issues,” such as with adolescents and reproductive health, where “we know that some parents have sign-in information for their teen’s portal,” he commented. With clinical notes now on full display, potential problems “may be out of our control.”
Still, the Sacramento-based physician and IT officer acknowledged that concerns about open notes may be a bit inflated. “I’ve been more worried about reassuring physicians that everything will be okay than what’s actually going to happen [as the law takes effect],” Dr. MacDonald said.
The OpenNotes organization is grant funded, and staff disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Change in writing style is not mandated
Change in writing style is not mandated
The mandate, called “open notes” by many, is part of the 21st Century Cures Act, a wide-ranging piece of federal health care legislation. The previous deadline of Nov. 2, 2020, for enacting open notes was extended last year because of the exigencies of the COVID-19 pandemic.
Organizations must provide access via patient portals to the following types of notes: consultations, discharge summaries, histories, physical examination findings, imaging narratives, laboratory and pathology report narratives, and procedure and progress notes. Noncompliant organizations will eventually be subject to fines from the Department of Health & Human Services for “information blocking.”
This news organization reported on the mandate in 2020, and some readers said it was an unwelcome intrusion into practice. Since then, this news organization has run additional open notes stories about physician concerns, a perspective essay addressing those fears, and a reader poll about the phenomenon.
Now, as the legislation turns into a practical clinical matter, there are five key points clinicians should consider.
Clinicians don’t have to change writing style.
The new law mandates timely patient access to notes and test results, but it doesn’t require that clinicians alter their writing, said Scott MacDonald, MD, an internist and electronic health record medical director at University of California Davis Health in Sacramento.
“You don’t have to change your notes,” he said. However, patients are now part of the note audience and some health care systems are directing clinicians to make patient-friendly style changes.
Everyday experience should guide clinicians when writing notes, said one expert.
“When you’re not sure [of how to write a note], just mirror the way you would speak in the office – that’s going to get you right, including for mental health issues,” advised Leonor Fernandez, MD, an internist at Beth Deaconess Israel Medical Center, Boston, in her “take-away” comments in the online video, How to Write an Open Note.
According to a 2020 Medscape poll of 1,050 physicians, a majority (56%) anticipate that they will write notes differently, knowing that patients can read them via open notes. Nearly two-thirds (64%) believe that this new wrinkle in medical records will increase their workload. However, actual practice suggests that this is true for a minority of practitioners, according to the results from a recent study of more than 1,000 physicians in Boston, Seattle, and rural Pennsylvania, who already work in open notes settings. Only about one-third (37%) reported “spending more time on documentation.”
Note writing is going to change because of the addition of the patient reader, and something will be lost, argued Steven Reidbord, MD, a psychiatrist in private practice in San Francisco. By watering down the language for patients, “you are trading away the technical precision and other advantages of having a professional language,” commented Dr. Reidbord, who blogs for Psychology Today and has criticized the open notes movement in the past.
However, years of investigation from OpenNotes, the Boston-based advocacy and research organization, indicates that there are many gains with patient-accessible notes, including improved medical record accuracy, greater medication adherence, and potentially improved health care disparities among a range of patient types. In a 2019 study, researchers said that worry and confusion among note-reading patients are uncommon (5% and 3%, respectively), which addresses two criticisms voiced by multiple people last year.
Some clinical notes can be withheld.
The new rules from the federal government permit information blocking if there is clear evidence that doing so “will substantially reduce the risk of harm” to patients or to other third parties, Tom Delbanco, MD, and Charlotte Blease, PhD, of OpenNotes in Boston wrote in a commentary in February 2021.
There are also state-level laws that can supersede the new U.S. law and block access to notes, points out MacDonald. For example, California law dictates that providers cannot post cancer test results without talking with the patient first.
The OpenNotes organization also points out that, with regard to sensitive psychotherapy notes that are separated from the rest of a medical record, those notes “can be kept from patients without their permission, and such rules vary state by state.”
Some patients are more likely readers.
Some patients are more likely to peer into their files than others, said Liz Salmi, senior strategist at OpenNotes, who is also a brain cancer patient.
“Those patients who have more serious or chronic conditions ... are more likely to read their notes,” she said in an interview.
A new study of nearly 6,000 medical oncology patients at the University of Wisconsin confirmed that opinion. Patients with incurable metastatic disease were much more likely than those with early-stage, curable disease to read notes. Notably, younger patients were more likely than older ones to access notes, likely the result of generational tech savvy.
Despite the unpredictability of serious disease such as cancer, oncology patients find satisfaction in reading their notes, say experts. “We’ve overwhelmingly heard that patients like it,” Thomas LeBlanc, MD, medical oncologist at Duke University, Durham, N.C., where all patients already have access to clinicians’ notes, told this news organization in 2018.
You are part of the avant garde.
The United States and Scandinavian countries are the world leaders in implementing open notes in clinical practice, Dr. Blease said in an interview.
“It’s a phenomenal achievement” to have enacted open notes nationally, she said. For example, there are no open notes in Northern Ireland, Dr. Blease’s home country, or most of Europe.
In the United States, there are more than 200 medical organizations, including at least one in every state, that were voluntarily providing open notes before April 5, including interstate giants such as Banner Health and big-name medical centers such as Cleveland Clinic.
It may be hard for the United States to top Sweden’s embrace of the practice. The national open notes program now has 7.2 million patient accounts in a country of 10 million people, noted Maria Häggland, PhD, of Uppsala (Sweden) MedTech Science Innovation Center during a webinar last year.
The start day will come, and you may not notice.
“When April 5 happens, something brand new is going to happen symbolically,” Ms. Salmi said. Its importance is hard to measure.
“Patients say they trust their doctor more because they understand their thinking with open notes. How do you value that? We don’t have metrics for that,” she said.
Dr. MacDonald suggested that open notes are both new and not new. In the fall of 2020, he predicted that the launch day would come, and few clinicians would notice, in part because many patients already access truncated information via patient portals.
However, there are “sensitive issues,” such as with adolescents and reproductive health, where “we know that some parents have sign-in information for their teen’s portal,” he commented. With clinical notes now on full display, potential problems “may be out of our control.”
Still, the Sacramento-based physician and IT officer acknowledged that concerns about open notes may be a bit inflated. “I’ve been more worried about reassuring physicians that everything will be okay than what’s actually going to happen [as the law takes effect],” Dr. MacDonald said.
The OpenNotes organization is grant funded, and staff disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The mandate, called “open notes” by many, is part of the 21st Century Cures Act, a wide-ranging piece of federal health care legislation. The previous deadline of Nov. 2, 2020, for enacting open notes was extended last year because of the exigencies of the COVID-19 pandemic.
Organizations must provide access via patient portals to the following types of notes: consultations, discharge summaries, histories, physical examination findings, imaging narratives, laboratory and pathology report narratives, and procedure and progress notes. Noncompliant organizations will eventually be subject to fines from the Department of Health & Human Services for “information blocking.”
This news organization reported on the mandate in 2020, and some readers said it was an unwelcome intrusion into practice. Since then, this news organization has run additional open notes stories about physician concerns, a perspective essay addressing those fears, and a reader poll about the phenomenon.
Now, as the legislation turns into a practical clinical matter, there are five key points clinicians should consider.
Clinicians don’t have to change writing style.
The new law mandates timely patient access to notes and test results, but it doesn’t require that clinicians alter their writing, said Scott MacDonald, MD, an internist and electronic health record medical director at University of California Davis Health in Sacramento.
“You don’t have to change your notes,” he said. However, patients are now part of the note audience and some health care systems are directing clinicians to make patient-friendly style changes.
Everyday experience should guide clinicians when writing notes, said one expert.
“When you’re not sure [of how to write a note], just mirror the way you would speak in the office – that’s going to get you right, including for mental health issues,” advised Leonor Fernandez, MD, an internist at Beth Deaconess Israel Medical Center, Boston, in her “take-away” comments in the online video, How to Write an Open Note.
According to a 2020 Medscape poll of 1,050 physicians, a majority (56%) anticipate that they will write notes differently, knowing that patients can read them via open notes. Nearly two-thirds (64%) believe that this new wrinkle in medical records will increase their workload. However, actual practice suggests that this is true for a minority of practitioners, according to the results from a recent study of more than 1,000 physicians in Boston, Seattle, and rural Pennsylvania, who already work in open notes settings. Only about one-third (37%) reported “spending more time on documentation.”
Note writing is going to change because of the addition of the patient reader, and something will be lost, argued Steven Reidbord, MD, a psychiatrist in private practice in San Francisco. By watering down the language for patients, “you are trading away the technical precision and other advantages of having a professional language,” commented Dr. Reidbord, who blogs for Psychology Today and has criticized the open notes movement in the past.
However, years of investigation from OpenNotes, the Boston-based advocacy and research organization, indicates that there are many gains with patient-accessible notes, including improved medical record accuracy, greater medication adherence, and potentially improved health care disparities among a range of patient types. In a 2019 study, researchers said that worry and confusion among note-reading patients are uncommon (5% and 3%, respectively), which addresses two criticisms voiced by multiple people last year.
Some clinical notes can be withheld.
The new rules from the federal government permit information blocking if there is clear evidence that doing so “will substantially reduce the risk of harm” to patients or to other third parties, Tom Delbanco, MD, and Charlotte Blease, PhD, of OpenNotes in Boston wrote in a commentary in February 2021.
There are also state-level laws that can supersede the new U.S. law and block access to notes, points out MacDonald. For example, California law dictates that providers cannot post cancer test results without talking with the patient first.
The OpenNotes organization also points out that, with regard to sensitive psychotherapy notes that are separated from the rest of a medical record, those notes “can be kept from patients without their permission, and such rules vary state by state.”
Some patients are more likely readers.
Some patients are more likely to peer into their files than others, said Liz Salmi, senior strategist at OpenNotes, who is also a brain cancer patient.
“Those patients who have more serious or chronic conditions ... are more likely to read their notes,” she said in an interview.
A new study of nearly 6,000 medical oncology patients at the University of Wisconsin confirmed that opinion. Patients with incurable metastatic disease were much more likely than those with early-stage, curable disease to read notes. Notably, younger patients were more likely than older ones to access notes, likely the result of generational tech savvy.
Despite the unpredictability of serious disease such as cancer, oncology patients find satisfaction in reading their notes, say experts. “We’ve overwhelmingly heard that patients like it,” Thomas LeBlanc, MD, medical oncologist at Duke University, Durham, N.C., where all patients already have access to clinicians’ notes, told this news organization in 2018.
You are part of the avant garde.
The United States and Scandinavian countries are the world leaders in implementing open notes in clinical practice, Dr. Blease said in an interview.
“It’s a phenomenal achievement” to have enacted open notes nationally, she said. For example, there are no open notes in Northern Ireland, Dr. Blease’s home country, or most of Europe.
In the United States, there are more than 200 medical organizations, including at least one in every state, that were voluntarily providing open notes before April 5, including interstate giants such as Banner Health and big-name medical centers such as Cleveland Clinic.
It may be hard for the United States to top Sweden’s embrace of the practice. The national open notes program now has 7.2 million patient accounts in a country of 10 million people, noted Maria Häggland, PhD, of Uppsala (Sweden) MedTech Science Innovation Center during a webinar last year.
The start day will come, and you may not notice.
“When April 5 happens, something brand new is going to happen symbolically,” Ms. Salmi said. Its importance is hard to measure.
“Patients say they trust their doctor more because they understand their thinking with open notes. How do you value that? We don’t have metrics for that,” she said.
Dr. MacDonald suggested that open notes are both new and not new. In the fall of 2020, he predicted that the launch day would come, and few clinicians would notice, in part because many patients already access truncated information via patient portals.
However, there are “sensitive issues,” such as with adolescents and reproductive health, where “we know that some parents have sign-in information for their teen’s portal,” he commented. With clinical notes now on full display, potential problems “may be out of our control.”
Still, the Sacramento-based physician and IT officer acknowledged that concerns about open notes may be a bit inflated. “I’ve been more worried about reassuring physicians that everything will be okay than what’s actually going to happen [as the law takes effect],” Dr. MacDonald said.
The OpenNotes organization is grant funded, and staff disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Delirium risk factors identified in ICU cancer patients
Hematology-oncology patients who receive treatment in the intensive care unit often develop delirium, and according to new findings, mechanical ventilation, high-dose corticosteroid use, and brain metastases were identified as independent risk factors.
Roughly half of all hematology-oncology patients who were admitted to the ICU experienced delirium, explained lead author Rachel Klosko, PharmD, PGY-2 cardiology pharmacy resident at the Ohio State University, Columbus.
“Delirium was associated with increased mortality, an increase in hospital length of stay, and increased length of stay in the ICU,” she said.
Dr. Klosko presented the study results at the at the Critical Care Congress sponsored by the Society of Critical Care Medicine (SCCM), which was held virtually this year.
Delirium is an acute and fluctuating disturbance of consciousness and cognition and fluctuates in severity. Critically ill patients are subject to numerous risk factors for delirium. “It can occur in independently of any known neurological disorder,” said Dr. Klosko, adding that its occurrence has been associated with poorer outcomes in ICU patients.
In this study, Dr. Klosko and colleagues sought to determine the incidence of delirium in cancer patients who were admitted to the ICU, as well as identify the associated risk factors and recognize potential consequences of the development of delirium in this patient population.
They conducted a single center, retrospective, cohort study that evaluated patients between the ages of 18 and 89 years who were admitted to the hematology-oncology medical or surgical ICU between July 1, 2018, and June 30, 2019.
The study’s primary endpoint was the incidence of delirium within 7 days of ICU admission, defined as two positive Confusion Assessment Method for the ICU (CAM-ICU) assessments within 24 hours. Patients identified with delirium were compared to those without it, for the evaluation of secondary endpoints that included hospital mortality and ICU and hospital length of stay. The researchers also sought to identify independent risk factors for delirium in this population.
A total of 244 patients were included in the final analysis. Of this group, 125 (51.2%) experienced delirium during their stay in the ICU, and 119 (48.8%) did not.
Mortality in the delirium group was significantly higher at 32.8% vs. 15.1% (P = .001). In addition, the delirium group was associated with significantly higher ICU length of stay (6 days vs. 3 days, P < .001) and hospital length of stay (21 days vs. 12 days, P < .001).
“When comparing the baseline characteristics between the two groups, the delirium group had a longer hospital length prior to ICU admission, a higher SOFA score, a higher rate of brain metastases, a higher rate of shock, and higher receipt of high-dose steroids, benzodiazepines, and immunotherapy,” said Dr. Klosko.
After multivariable regression, four variables were included in the final model. Among patients with delirium, the SOFA score increased by 25% (odds ratio[OR] 1.25, P < .001), while the odds of delirium were almost four times higher among those treated with high-dose corticosteroids (OR 3.79, P = .004). Delirium was also eight times higher (OR 8.48, P < .001) among those who received mechanical ventilation and five times higher in (OR 5.38, P = .015) in patients with brain metastases.
Dr. Klosko noted that the main limitations for this study were that it was a single center retrospective analysis, and that patients were reviewed within the first 7 days of ICU admission. “This potentially missed patients who developed delirium outside of this time frame,” she said. In addition, “too few patients received high-dose benzodiazepines,” and “none of the patients received continuous neuromuscular blockade.”
However, in “contrast to these limitations, this is the largest study to date that has analyzed delirium in this population,” Dr. Klosko said.
Commenting on the study, Brenda Pun, DNP, RN, director of data quality at the Vanderbilt Critical Illness, Brain Dysfunction, and Survivorship Center, Nashville, Tenn., pointed out that the goal of this study was to describe delirium in this specific population. “But I will take a step backward and say that they are just confirming that these patients look like other ICU patients in many regards,” she said.
She explained that the sicker patients are, the higher the rates of delirium. “We have implemented strategies to lower these rates, and they have improved,” Dr. Pun said. “Ten years ago, I would say that 80% of patients who were on a ventilator would have delirium but now the rates are around 50% and that’s what we are typically seeing now.”
Dr. Pun emphasized that this study shows that delirium is like the “canary in the coal mine” or a red flag. “It’s a sign that something is wrong and that we need to pay attention, because the patient’s outcome may be worse,” she said. “So this is saying that we need to see if there is something that can be changed or modified to decrease the incidence of delirium—these are important questions.”
There was no outside sponsor. The authors had no disclosures. Dr. Pun has no disclosures.
Hematology-oncology patients who receive treatment in the intensive care unit often develop delirium, and according to new findings, mechanical ventilation, high-dose corticosteroid use, and brain metastases were identified as independent risk factors.
Roughly half of all hematology-oncology patients who were admitted to the ICU experienced delirium, explained lead author Rachel Klosko, PharmD, PGY-2 cardiology pharmacy resident at the Ohio State University, Columbus.
“Delirium was associated with increased mortality, an increase in hospital length of stay, and increased length of stay in the ICU,” she said.
Dr. Klosko presented the study results at the at the Critical Care Congress sponsored by the Society of Critical Care Medicine (SCCM), which was held virtually this year.
Delirium is an acute and fluctuating disturbance of consciousness and cognition and fluctuates in severity. Critically ill patients are subject to numerous risk factors for delirium. “It can occur in independently of any known neurological disorder,” said Dr. Klosko, adding that its occurrence has been associated with poorer outcomes in ICU patients.
In this study, Dr. Klosko and colleagues sought to determine the incidence of delirium in cancer patients who were admitted to the ICU, as well as identify the associated risk factors and recognize potential consequences of the development of delirium in this patient population.
They conducted a single center, retrospective, cohort study that evaluated patients between the ages of 18 and 89 years who were admitted to the hematology-oncology medical or surgical ICU between July 1, 2018, and June 30, 2019.
The study’s primary endpoint was the incidence of delirium within 7 days of ICU admission, defined as two positive Confusion Assessment Method for the ICU (CAM-ICU) assessments within 24 hours. Patients identified with delirium were compared to those without it, for the evaluation of secondary endpoints that included hospital mortality and ICU and hospital length of stay. The researchers also sought to identify independent risk factors for delirium in this population.
A total of 244 patients were included in the final analysis. Of this group, 125 (51.2%) experienced delirium during their stay in the ICU, and 119 (48.8%) did not.
Mortality in the delirium group was significantly higher at 32.8% vs. 15.1% (P = .001). In addition, the delirium group was associated with significantly higher ICU length of stay (6 days vs. 3 days, P < .001) and hospital length of stay (21 days vs. 12 days, P < .001).
“When comparing the baseline characteristics between the two groups, the delirium group had a longer hospital length prior to ICU admission, a higher SOFA score, a higher rate of brain metastases, a higher rate of shock, and higher receipt of high-dose steroids, benzodiazepines, and immunotherapy,” said Dr. Klosko.
After multivariable regression, four variables were included in the final model. Among patients with delirium, the SOFA score increased by 25% (odds ratio[OR] 1.25, P < .001), while the odds of delirium were almost four times higher among those treated with high-dose corticosteroids (OR 3.79, P = .004). Delirium was also eight times higher (OR 8.48, P < .001) among those who received mechanical ventilation and five times higher in (OR 5.38, P = .015) in patients with brain metastases.
Dr. Klosko noted that the main limitations for this study were that it was a single center retrospective analysis, and that patients were reviewed within the first 7 days of ICU admission. “This potentially missed patients who developed delirium outside of this time frame,” she said. In addition, “too few patients received high-dose benzodiazepines,” and “none of the patients received continuous neuromuscular blockade.”
However, in “contrast to these limitations, this is the largest study to date that has analyzed delirium in this population,” Dr. Klosko said.
Commenting on the study, Brenda Pun, DNP, RN, director of data quality at the Vanderbilt Critical Illness, Brain Dysfunction, and Survivorship Center, Nashville, Tenn., pointed out that the goal of this study was to describe delirium in this specific population. “But I will take a step backward and say that they are just confirming that these patients look like other ICU patients in many regards,” she said.
She explained that the sicker patients are, the higher the rates of delirium. “We have implemented strategies to lower these rates, and they have improved,” Dr. Pun said. “Ten years ago, I would say that 80% of patients who were on a ventilator would have delirium but now the rates are around 50% and that’s what we are typically seeing now.”
Dr. Pun emphasized that this study shows that delirium is like the “canary in the coal mine” or a red flag. “It’s a sign that something is wrong and that we need to pay attention, because the patient’s outcome may be worse,” she said. “So this is saying that we need to see if there is something that can be changed or modified to decrease the incidence of delirium—these are important questions.”
There was no outside sponsor. The authors had no disclosures. Dr. Pun has no disclosures.
Hematology-oncology patients who receive treatment in the intensive care unit often develop delirium, and according to new findings, mechanical ventilation, high-dose corticosteroid use, and brain metastases were identified as independent risk factors.
Roughly half of all hematology-oncology patients who were admitted to the ICU experienced delirium, explained lead author Rachel Klosko, PharmD, PGY-2 cardiology pharmacy resident at the Ohio State University, Columbus.
“Delirium was associated with increased mortality, an increase in hospital length of stay, and increased length of stay in the ICU,” she said.
Dr. Klosko presented the study results at the at the Critical Care Congress sponsored by the Society of Critical Care Medicine (SCCM), which was held virtually this year.
Delirium is an acute and fluctuating disturbance of consciousness and cognition and fluctuates in severity. Critically ill patients are subject to numerous risk factors for delirium. “It can occur in independently of any known neurological disorder,” said Dr. Klosko, adding that its occurrence has been associated with poorer outcomes in ICU patients.
In this study, Dr. Klosko and colleagues sought to determine the incidence of delirium in cancer patients who were admitted to the ICU, as well as identify the associated risk factors and recognize potential consequences of the development of delirium in this patient population.
They conducted a single center, retrospective, cohort study that evaluated patients between the ages of 18 and 89 years who were admitted to the hematology-oncology medical or surgical ICU between July 1, 2018, and June 30, 2019.
The study’s primary endpoint was the incidence of delirium within 7 days of ICU admission, defined as two positive Confusion Assessment Method for the ICU (CAM-ICU) assessments within 24 hours. Patients identified with delirium were compared to those without it, for the evaluation of secondary endpoints that included hospital mortality and ICU and hospital length of stay. The researchers also sought to identify independent risk factors for delirium in this population.
A total of 244 patients were included in the final analysis. Of this group, 125 (51.2%) experienced delirium during their stay in the ICU, and 119 (48.8%) did not.
Mortality in the delirium group was significantly higher at 32.8% vs. 15.1% (P = .001). In addition, the delirium group was associated with significantly higher ICU length of stay (6 days vs. 3 days, P < .001) and hospital length of stay (21 days vs. 12 days, P < .001).
“When comparing the baseline characteristics between the two groups, the delirium group had a longer hospital length prior to ICU admission, a higher SOFA score, a higher rate of brain metastases, a higher rate of shock, and higher receipt of high-dose steroids, benzodiazepines, and immunotherapy,” said Dr. Klosko.
After multivariable regression, four variables were included in the final model. Among patients with delirium, the SOFA score increased by 25% (odds ratio[OR] 1.25, P < .001), while the odds of delirium were almost four times higher among those treated with high-dose corticosteroids (OR 3.79, P = .004). Delirium was also eight times higher (OR 8.48, P < .001) among those who received mechanical ventilation and five times higher in (OR 5.38, P = .015) in patients with brain metastases.
Dr. Klosko noted that the main limitations for this study were that it was a single center retrospective analysis, and that patients were reviewed within the first 7 days of ICU admission. “This potentially missed patients who developed delirium outside of this time frame,” she said. In addition, “too few patients received high-dose benzodiazepines,” and “none of the patients received continuous neuromuscular blockade.”
However, in “contrast to these limitations, this is the largest study to date that has analyzed delirium in this population,” Dr. Klosko said.
Commenting on the study, Brenda Pun, DNP, RN, director of data quality at the Vanderbilt Critical Illness, Brain Dysfunction, and Survivorship Center, Nashville, Tenn., pointed out that the goal of this study was to describe delirium in this specific population. “But I will take a step backward and say that they are just confirming that these patients look like other ICU patients in many regards,” she said.
She explained that the sicker patients are, the higher the rates of delirium. “We have implemented strategies to lower these rates, and they have improved,” Dr. Pun said. “Ten years ago, I would say that 80% of patients who were on a ventilator would have delirium but now the rates are around 50% and that’s what we are typically seeing now.”
Dr. Pun emphasized that this study shows that delirium is like the “canary in the coal mine” or a red flag. “It’s a sign that something is wrong and that we need to pay attention, because the patient’s outcome may be worse,” she said. “So this is saying that we need to see if there is something that can be changed or modified to decrease the incidence of delirium—these are important questions.”
There was no outside sponsor. The authors had no disclosures. Dr. Pun has no disclosures.
FROM CCC50
Paving the way for diversity in clinical trials
“I’m the first person in my circle of family and friends to participate in a clinical trial.”
Five years ago, Rhonda Long was diagnosed with cholangiocarcinoma, a rare bile duct cancer that’s seen in only about 8,000 Americans each year.
At the time, Mrs. Long, who is Black, said her doctor in Dayton, Ohio, told her she was not a candidate for surgery and suggested palliative care. After seeking a second opinion at Duke University Medical Center, Durham, N.C., where her sister worked, the 51-year-old wife and mother of two had surgery, radiation, and chemotherapy there in North Carolina. When the chemo stopped working after 3 months, her oncologist at Duke referred her to a colleague at Massachusetts General Hospital in Boston, where she was accepted into a clinical trial.
“In 2019, I traveled to Boston from Dayton, Ohio, every 3 weeks for labs and scans, to make sure that the drug wasn’t doing more harm than good, making sure that the drug as developed was maintaining, shrinking, or even eliminating the disease. Physically and financially, it takes a toll on you and loved ones.”
Her medical insurance did not cover the direct expenses from the clinical trial, and she was spending $1,000-$1,500 each trip. Sometimes they drove the 15 hours to Boston, and sometimes they flew on the cheapest flight they could find.
It’s not an unfamiliar story: people traveling, often long distances, to take part in clinical trials they hope will save their lives.
The Lazarex Cancer Foundation of Danville, Calif., helped Mrs. Long do just that.
Marya Shegog, PhD, health equity and diversity coordinator at Lazarex, said that a patient travels an average of 500 miles to participate in a trial.
The financial hurdles often prevent patients from taking part in clinical trials, Dr. Shegog said. “When you are sick, and you have a disease that may be terminal, you start thinking about setting your things in order.”
Many patients have to make a decision.
“Do I bankrupt my family on trying and hoping that this drug works and helps me live longer, or do I start setting things in order so that when I’m gone, they’re okay or at least better than if I wouldn’t have spent all the money traveling back and forth.”
Dr. Shegog, a 17-year cancer survivor, says when she was battling cervical cancer, a clinical trial was never offered or explored.
Lazarex has been helping cancer patients who have run out of options for 15 years. It identifies clinical trial opportunities and reimburses patients for all travel costs. Last year, Lazarex reimbursed more than 1,000 cancer patients. And it has supported more than 6,000 people since opening its doors.
“Lazarex exists to help remove the barriers of people not being able to participate in trials,” Dr. Shegog said. “It’s systemic that the medical system does not treat patients the same and oftentimes does not offer or make aware the opportunities for African Americans to participate.”
But now, thanks in part to COVID-19, new possibilities are taking shape. The pandemic has changed the landscape for trials, forcing many of them to go virtual, which allows patients to schedule telehealth visits and get some services like bloodwork and CT or MRI scans closer to home. Mrs. Long’s trial eventually went virtual.
“It was absolutely fantastic,” she said. “Having the trial locally, it saves us money, it saves wear and tear on my body. Being in the car, being in an airport or in a plane and in a hotel, all of that wears on you physically.”
The move to virtual studies may have lasting effects on research and treatment.
“The current pandemic has forced us to reexamine all of the traditional burdens we place on patients as it relates to receiving cancer treatment,” said Hala Borno, MD, an assistant professor of medicine at the University of California, San Francisco. “Whether they’re coming to our health care facility to see a clinician, for diagnostics such as blood draws and scans, or to receive therapy, this pandemic has challenged us to explore other possibilities that minimize the risk of exposure to SARS-CoV-2. What I find striking is that it has helped us operationalize use of telemedicine and the delivery of care closer to home.”
This is especially encouraging news for minority patients whose participation in trials has for years lagged well behind that of Whites.
But travel is not the only reason. Racial disparities in clinical trials have long been an issue that’s just another part of the implicit bias in health care.
Compared with White people, Black people are largely at higher risk for heart disease, cancer, stroke, diabetes, asthma, and even mental health problems.
And it’s not just African Americans. Asians, Hispanics, Native Americans, and Alaska Natives are all underrepresented in trials at a time when there is growing evidence that drugs may have different effects on different populations.
Dr. Borno is an oncologist who specializes in prostate cancer, a disease that she says shows a “significant disparity,” where Black men are two times more likely to die from advanced prostate cancer, compared with white men. Yet Black men make up just 3% of advanced therapeutic trials.
“A lack of diversity and inclusion in clinical trials is unacceptable,” she said. “If we continue to underrecruit racial/ethnic minorities and older adults to therapeutic clinical trials, we will not be powered to make valid conclusions regarding safety and efficacy in those patient populations. As a result, we can do harm.”
Dr. Borno said that telehealth and telemedicine are not cure-alls, and digital health solutions don’t work for all patients. Approaches, she says, must be tailored to the individual, or disparities could worsen.
In 2020, the Food and Drug Administration approved 53 new drugs. Overall, 32,000 patients took part in these trials. On average, 75% were White, 8% were Black, 6% were Asian, and 11% were Hispanic.
Here’s one stark example of the issue. In 2015, the FDA approved ixazomib (Ninlaro), a promising new drug for multiple myeloma, a blood cancer that affects Black people at disproportionately higher rates than White people. In the United States, one in five people diagnosed with multiple myeloma are Black people. They are more than twice as likely to get the disease as White people. Yet during the clinical trial of 722 participants, only 13 patients, or 1.8%, were Black.
The American Cancer Society estimates that more than 600,000 Americans will die from cancer this year. Historically, Black Americans have the highest death rate and the shortest survival of any racial or ethnic group, stemming largely, it concluded, from centuries of structural racism.
According to Jamie Freedman, MD, head of U.S. medical affairs at Genentech, a global pharmaceutical company, the lack of diversity is often tied to where studies are run.
“Companies tend to choose major academic medical centers where there is a high volume of clinical trial work. When you go to the same tried and true hospitals repeatedly, the pool of patients becomes very homogeneous and tends to be primarily white,” he said. “It’s critical to bring more trials into the community setting by including new sites that can reach underrepresented groups, and Genentech is making significant progress in that area.”
Dr. Freedman believes that, while access is a big hurdle, it doesn’t end there.
“Many patients have a lack of trust in the health care system,” he said. “There are also issues around underserved communities being able to afford quality care, so it’s important to keep time and financial burdens in mind when designing trials to help mitigate barriers such as travel, parking, time off work, and child care.”
Genentech started its diversity and inclusion effort several years ago. Dr. Freeman said that, until more trials become diverse, Black Americans will continue to pay the price. “I think they’re losing their lives in part due to lack of access to these trials. And that is why Genentech and all of us in the health care industry need to change how we design and enroll these studies. We have a long way to go, but I think the steps we’re taking are leading us in the right direction.”
Jennifer Jones-McMeans, PhD, director of global clinical affairs at Abbott Pharmaceuticals, is a clinical research scientist who has designed and led many clinical trials.
She said that Abbott is actively working on solutions.
“We have designed our trials to reduce the barriers to participation and expand access,” she said. “This can be as simple as providing transportation services or home visits for those who are housebound. We’re taking it a step further and providing home health services where someone comes to the home and provides follow-up visits there.”
They also provide interpretation services to address any language barriers.
“We are reaching out to a new set of talented investigators who work closely with underrepresented communities. They are very much wedded and supportive of the communities they treat. By working with doctors within these communities, it expands access to new therapies.”
Spokesperson Keanna Ghazvini said that Pfizer Pharmaceuticals is also committed to increasing minority participation in trials.
“We know that if historically underserved populations are left out of clinical trials, they risk not benefiting from medical breakthroughs down the line,” she said.
The National Institutes of Health’s National Library of Medicine maintains the clinicaltrials.gov database.
There, you can find information on nearly 372,000 publicly and privately supported clinical trials happening in all 50 states and 219 countries. Many are funded by the NIH, but not all of these studies have been evaluated by the U.S. government.
Andrea Denicoff, a nurse consultant at the National Cancer Institute and head of clinical trials operations for the NCI’s National Clinical Trials Network, has been involved in clinical research at the NIH for 35 years.
“It’s really important that our publicly funded trials represent the people of the country,” she said. “There are some cancers that we’re doing a good job in enrolling minorities, and other cancers we need to do a much better job in having a diverse representation in our trials.”
Ms. Denicoff believed opening trials in places where people live is key, but having a diverse clinical trials team is as important.
“We need to reinforce that cancer centers across the country have open doors, and anyone with cancer feels comfortable getting care at that center, and that also includes discussing the option to participate in clinical trials when one might be available. We know from research that when people are invited and asked about trial participation and educated about them, they’ll be much more interested in joining them.”
Ms. Denicoff said that, during the pandemic, the NCI quickly came up with guidance to allow trial sites to send patients their oral study drugs and set up virtual visits. She believes it may help increase future access.
‘Lola Fashoyin-Aje, MD, associate director for science and policy to address disparities in the Oncology Center of Excellence at the FDA, says the agency firmly believes clinical trials should represent the patients who will ultimately get the drug if it’s approved.
But the FDA’s power to require diversity in trials is limited.
“It is important to point out that there are legal constraints which limit’s FDA’s authority to require specific proportional representation in clinical trials by demographic factors,” Dr. Fashoyin-Aje said.
Still, some researchers feel the FDA should play a bigger role. The question is: Should diversity be mandated?
Rhonda Long is now back in Boston to start a new trial, with a new drug that targets her specific mutation. She will be there for 2 months. Once again, Lazarex will help cover some of the cost.
She wants people of color to understand that they are missing out on the promise of new cancer drugs and extended life.
“I feel like there’s not enough emphasis on clinical trials, I don’t believe there’s enough emphasis on second opinions, I don’t think there’s enough emphasis that medicine happens outside our borders, outside of our communities. Clinical trials that don’t have a broad range of participants, how do we know how effective they are if Black and brown people, Asian or Latin American people aren’t represented in the trial?”
And with more trials adopting virtual elements, she said it’s time for minorities to get on board.
Dr. Freedman believed the groundwork is being laid for that to happen. “I don’t think we’ll ever return back to the way we used to do things, where everything has to be done at the clinical trial site. I just don’t think we’re ever going back.”
A version of this article first appeared on WebMD.com.
“I’m the first person in my circle of family and friends to participate in a clinical trial.”
Five years ago, Rhonda Long was diagnosed with cholangiocarcinoma, a rare bile duct cancer that’s seen in only about 8,000 Americans each year.
At the time, Mrs. Long, who is Black, said her doctor in Dayton, Ohio, told her she was not a candidate for surgery and suggested palliative care. After seeking a second opinion at Duke University Medical Center, Durham, N.C., where her sister worked, the 51-year-old wife and mother of two had surgery, radiation, and chemotherapy there in North Carolina. When the chemo stopped working after 3 months, her oncologist at Duke referred her to a colleague at Massachusetts General Hospital in Boston, where she was accepted into a clinical trial.
“In 2019, I traveled to Boston from Dayton, Ohio, every 3 weeks for labs and scans, to make sure that the drug wasn’t doing more harm than good, making sure that the drug as developed was maintaining, shrinking, or even eliminating the disease. Physically and financially, it takes a toll on you and loved ones.”
Her medical insurance did not cover the direct expenses from the clinical trial, and she was spending $1,000-$1,500 each trip. Sometimes they drove the 15 hours to Boston, and sometimes they flew on the cheapest flight they could find.
It’s not an unfamiliar story: people traveling, often long distances, to take part in clinical trials they hope will save their lives.
The Lazarex Cancer Foundation of Danville, Calif., helped Mrs. Long do just that.
Marya Shegog, PhD, health equity and diversity coordinator at Lazarex, said that a patient travels an average of 500 miles to participate in a trial.
The financial hurdles often prevent patients from taking part in clinical trials, Dr. Shegog said. “When you are sick, and you have a disease that may be terminal, you start thinking about setting your things in order.”
Many patients have to make a decision.
“Do I bankrupt my family on trying and hoping that this drug works and helps me live longer, or do I start setting things in order so that when I’m gone, they’re okay or at least better than if I wouldn’t have spent all the money traveling back and forth.”
Dr. Shegog, a 17-year cancer survivor, says when she was battling cervical cancer, a clinical trial was never offered or explored.
Lazarex has been helping cancer patients who have run out of options for 15 years. It identifies clinical trial opportunities and reimburses patients for all travel costs. Last year, Lazarex reimbursed more than 1,000 cancer patients. And it has supported more than 6,000 people since opening its doors.
“Lazarex exists to help remove the barriers of people not being able to participate in trials,” Dr. Shegog said. “It’s systemic that the medical system does not treat patients the same and oftentimes does not offer or make aware the opportunities for African Americans to participate.”
But now, thanks in part to COVID-19, new possibilities are taking shape. The pandemic has changed the landscape for trials, forcing many of them to go virtual, which allows patients to schedule telehealth visits and get some services like bloodwork and CT or MRI scans closer to home. Mrs. Long’s trial eventually went virtual.
“It was absolutely fantastic,” she said. “Having the trial locally, it saves us money, it saves wear and tear on my body. Being in the car, being in an airport or in a plane and in a hotel, all of that wears on you physically.”
The move to virtual studies may have lasting effects on research and treatment.
“The current pandemic has forced us to reexamine all of the traditional burdens we place on patients as it relates to receiving cancer treatment,” said Hala Borno, MD, an assistant professor of medicine at the University of California, San Francisco. “Whether they’re coming to our health care facility to see a clinician, for diagnostics such as blood draws and scans, or to receive therapy, this pandemic has challenged us to explore other possibilities that minimize the risk of exposure to SARS-CoV-2. What I find striking is that it has helped us operationalize use of telemedicine and the delivery of care closer to home.”
This is especially encouraging news for minority patients whose participation in trials has for years lagged well behind that of Whites.
But travel is not the only reason. Racial disparities in clinical trials have long been an issue that’s just another part of the implicit bias in health care.
Compared with White people, Black people are largely at higher risk for heart disease, cancer, stroke, diabetes, asthma, and even mental health problems.
And it’s not just African Americans. Asians, Hispanics, Native Americans, and Alaska Natives are all underrepresented in trials at a time when there is growing evidence that drugs may have different effects on different populations.
Dr. Borno is an oncologist who specializes in prostate cancer, a disease that she says shows a “significant disparity,” where Black men are two times more likely to die from advanced prostate cancer, compared with white men. Yet Black men make up just 3% of advanced therapeutic trials.
“A lack of diversity and inclusion in clinical trials is unacceptable,” she said. “If we continue to underrecruit racial/ethnic minorities and older adults to therapeutic clinical trials, we will not be powered to make valid conclusions regarding safety and efficacy in those patient populations. As a result, we can do harm.”
Dr. Borno said that telehealth and telemedicine are not cure-alls, and digital health solutions don’t work for all patients. Approaches, she says, must be tailored to the individual, or disparities could worsen.
In 2020, the Food and Drug Administration approved 53 new drugs. Overall, 32,000 patients took part in these trials. On average, 75% were White, 8% were Black, 6% were Asian, and 11% were Hispanic.
Here’s one stark example of the issue. In 2015, the FDA approved ixazomib (Ninlaro), a promising new drug for multiple myeloma, a blood cancer that affects Black people at disproportionately higher rates than White people. In the United States, one in five people diagnosed with multiple myeloma are Black people. They are more than twice as likely to get the disease as White people. Yet during the clinical trial of 722 participants, only 13 patients, or 1.8%, were Black.
The American Cancer Society estimates that more than 600,000 Americans will die from cancer this year. Historically, Black Americans have the highest death rate and the shortest survival of any racial or ethnic group, stemming largely, it concluded, from centuries of structural racism.
According to Jamie Freedman, MD, head of U.S. medical affairs at Genentech, a global pharmaceutical company, the lack of diversity is often tied to where studies are run.
“Companies tend to choose major academic medical centers where there is a high volume of clinical trial work. When you go to the same tried and true hospitals repeatedly, the pool of patients becomes very homogeneous and tends to be primarily white,” he said. “It’s critical to bring more trials into the community setting by including new sites that can reach underrepresented groups, and Genentech is making significant progress in that area.”
Dr. Freedman believes that, while access is a big hurdle, it doesn’t end there.
“Many patients have a lack of trust in the health care system,” he said. “There are also issues around underserved communities being able to afford quality care, so it’s important to keep time and financial burdens in mind when designing trials to help mitigate barriers such as travel, parking, time off work, and child care.”
Genentech started its diversity and inclusion effort several years ago. Dr. Freeman said that, until more trials become diverse, Black Americans will continue to pay the price. “I think they’re losing their lives in part due to lack of access to these trials. And that is why Genentech and all of us in the health care industry need to change how we design and enroll these studies. We have a long way to go, but I think the steps we’re taking are leading us in the right direction.”
Jennifer Jones-McMeans, PhD, director of global clinical affairs at Abbott Pharmaceuticals, is a clinical research scientist who has designed and led many clinical trials.
She said that Abbott is actively working on solutions.
“We have designed our trials to reduce the barriers to participation and expand access,” she said. “This can be as simple as providing transportation services or home visits for those who are housebound. We’re taking it a step further and providing home health services where someone comes to the home and provides follow-up visits there.”
They also provide interpretation services to address any language barriers.
“We are reaching out to a new set of talented investigators who work closely with underrepresented communities. They are very much wedded and supportive of the communities they treat. By working with doctors within these communities, it expands access to new therapies.”
Spokesperson Keanna Ghazvini said that Pfizer Pharmaceuticals is also committed to increasing minority participation in trials.
“We know that if historically underserved populations are left out of clinical trials, they risk not benefiting from medical breakthroughs down the line,” she said.
The National Institutes of Health’s National Library of Medicine maintains the clinicaltrials.gov database.
There, you can find information on nearly 372,000 publicly and privately supported clinical trials happening in all 50 states and 219 countries. Many are funded by the NIH, but not all of these studies have been evaluated by the U.S. government.
Andrea Denicoff, a nurse consultant at the National Cancer Institute and head of clinical trials operations for the NCI’s National Clinical Trials Network, has been involved in clinical research at the NIH for 35 years.
“It’s really important that our publicly funded trials represent the people of the country,” she said. “There are some cancers that we’re doing a good job in enrolling minorities, and other cancers we need to do a much better job in having a diverse representation in our trials.”
Ms. Denicoff believed opening trials in places where people live is key, but having a diverse clinical trials team is as important.
“We need to reinforce that cancer centers across the country have open doors, and anyone with cancer feels comfortable getting care at that center, and that also includes discussing the option to participate in clinical trials when one might be available. We know from research that when people are invited and asked about trial participation and educated about them, they’ll be much more interested in joining them.”
Ms. Denicoff said that, during the pandemic, the NCI quickly came up with guidance to allow trial sites to send patients their oral study drugs and set up virtual visits. She believes it may help increase future access.
‘Lola Fashoyin-Aje, MD, associate director for science and policy to address disparities in the Oncology Center of Excellence at the FDA, says the agency firmly believes clinical trials should represent the patients who will ultimately get the drug if it’s approved.
But the FDA’s power to require diversity in trials is limited.
“It is important to point out that there are legal constraints which limit’s FDA’s authority to require specific proportional representation in clinical trials by demographic factors,” Dr. Fashoyin-Aje said.
Still, some researchers feel the FDA should play a bigger role. The question is: Should diversity be mandated?
Rhonda Long is now back in Boston to start a new trial, with a new drug that targets her specific mutation. She will be there for 2 months. Once again, Lazarex will help cover some of the cost.
She wants people of color to understand that they are missing out on the promise of new cancer drugs and extended life.
“I feel like there’s not enough emphasis on clinical trials, I don’t believe there’s enough emphasis on second opinions, I don’t think there’s enough emphasis that medicine happens outside our borders, outside of our communities. Clinical trials that don’t have a broad range of participants, how do we know how effective they are if Black and brown people, Asian or Latin American people aren’t represented in the trial?”
And with more trials adopting virtual elements, she said it’s time for minorities to get on board.
Dr. Freedman believed the groundwork is being laid for that to happen. “I don’t think we’ll ever return back to the way we used to do things, where everything has to be done at the clinical trial site. I just don’t think we’re ever going back.”
A version of this article first appeared on WebMD.com.
“I’m the first person in my circle of family and friends to participate in a clinical trial.”
Five years ago, Rhonda Long was diagnosed with cholangiocarcinoma, a rare bile duct cancer that’s seen in only about 8,000 Americans each year.
At the time, Mrs. Long, who is Black, said her doctor in Dayton, Ohio, told her she was not a candidate for surgery and suggested palliative care. After seeking a second opinion at Duke University Medical Center, Durham, N.C., where her sister worked, the 51-year-old wife and mother of two had surgery, radiation, and chemotherapy there in North Carolina. When the chemo stopped working after 3 months, her oncologist at Duke referred her to a colleague at Massachusetts General Hospital in Boston, where she was accepted into a clinical trial.
“In 2019, I traveled to Boston from Dayton, Ohio, every 3 weeks for labs and scans, to make sure that the drug wasn’t doing more harm than good, making sure that the drug as developed was maintaining, shrinking, or even eliminating the disease. Physically and financially, it takes a toll on you and loved ones.”
Her medical insurance did not cover the direct expenses from the clinical trial, and she was spending $1,000-$1,500 each trip. Sometimes they drove the 15 hours to Boston, and sometimes they flew on the cheapest flight they could find.
It’s not an unfamiliar story: people traveling, often long distances, to take part in clinical trials they hope will save their lives.
The Lazarex Cancer Foundation of Danville, Calif., helped Mrs. Long do just that.
Marya Shegog, PhD, health equity and diversity coordinator at Lazarex, said that a patient travels an average of 500 miles to participate in a trial.
The financial hurdles often prevent patients from taking part in clinical trials, Dr. Shegog said. “When you are sick, and you have a disease that may be terminal, you start thinking about setting your things in order.”
Many patients have to make a decision.
“Do I bankrupt my family on trying and hoping that this drug works and helps me live longer, or do I start setting things in order so that when I’m gone, they’re okay or at least better than if I wouldn’t have spent all the money traveling back and forth.”
Dr. Shegog, a 17-year cancer survivor, says when she was battling cervical cancer, a clinical trial was never offered or explored.
Lazarex has been helping cancer patients who have run out of options for 15 years. It identifies clinical trial opportunities and reimburses patients for all travel costs. Last year, Lazarex reimbursed more than 1,000 cancer patients. And it has supported more than 6,000 people since opening its doors.
“Lazarex exists to help remove the barriers of people not being able to participate in trials,” Dr. Shegog said. “It’s systemic that the medical system does not treat patients the same and oftentimes does not offer or make aware the opportunities for African Americans to participate.”
But now, thanks in part to COVID-19, new possibilities are taking shape. The pandemic has changed the landscape for trials, forcing many of them to go virtual, which allows patients to schedule telehealth visits and get some services like bloodwork and CT or MRI scans closer to home. Mrs. Long’s trial eventually went virtual.
“It was absolutely fantastic,” she said. “Having the trial locally, it saves us money, it saves wear and tear on my body. Being in the car, being in an airport or in a plane and in a hotel, all of that wears on you physically.”
The move to virtual studies may have lasting effects on research and treatment.
“The current pandemic has forced us to reexamine all of the traditional burdens we place on patients as it relates to receiving cancer treatment,” said Hala Borno, MD, an assistant professor of medicine at the University of California, San Francisco. “Whether they’re coming to our health care facility to see a clinician, for diagnostics such as blood draws and scans, or to receive therapy, this pandemic has challenged us to explore other possibilities that minimize the risk of exposure to SARS-CoV-2. What I find striking is that it has helped us operationalize use of telemedicine and the delivery of care closer to home.”
This is especially encouraging news for minority patients whose participation in trials has for years lagged well behind that of Whites.
But travel is not the only reason. Racial disparities in clinical trials have long been an issue that’s just another part of the implicit bias in health care.
Compared with White people, Black people are largely at higher risk for heart disease, cancer, stroke, diabetes, asthma, and even mental health problems.
And it’s not just African Americans. Asians, Hispanics, Native Americans, and Alaska Natives are all underrepresented in trials at a time when there is growing evidence that drugs may have different effects on different populations.
Dr. Borno is an oncologist who specializes in prostate cancer, a disease that she says shows a “significant disparity,” where Black men are two times more likely to die from advanced prostate cancer, compared with white men. Yet Black men make up just 3% of advanced therapeutic trials.
“A lack of diversity and inclusion in clinical trials is unacceptable,” she said. “If we continue to underrecruit racial/ethnic minorities and older adults to therapeutic clinical trials, we will not be powered to make valid conclusions regarding safety and efficacy in those patient populations. As a result, we can do harm.”
Dr. Borno said that telehealth and telemedicine are not cure-alls, and digital health solutions don’t work for all patients. Approaches, she says, must be tailored to the individual, or disparities could worsen.
In 2020, the Food and Drug Administration approved 53 new drugs. Overall, 32,000 patients took part in these trials. On average, 75% were White, 8% were Black, 6% were Asian, and 11% were Hispanic.
Here’s one stark example of the issue. In 2015, the FDA approved ixazomib (Ninlaro), a promising new drug for multiple myeloma, a blood cancer that affects Black people at disproportionately higher rates than White people. In the United States, one in five people diagnosed with multiple myeloma are Black people. They are more than twice as likely to get the disease as White people. Yet during the clinical trial of 722 participants, only 13 patients, or 1.8%, were Black.
The American Cancer Society estimates that more than 600,000 Americans will die from cancer this year. Historically, Black Americans have the highest death rate and the shortest survival of any racial or ethnic group, stemming largely, it concluded, from centuries of structural racism.
According to Jamie Freedman, MD, head of U.S. medical affairs at Genentech, a global pharmaceutical company, the lack of diversity is often tied to where studies are run.
“Companies tend to choose major academic medical centers where there is a high volume of clinical trial work. When you go to the same tried and true hospitals repeatedly, the pool of patients becomes very homogeneous and tends to be primarily white,” he said. “It’s critical to bring more trials into the community setting by including new sites that can reach underrepresented groups, and Genentech is making significant progress in that area.”
Dr. Freedman believes that, while access is a big hurdle, it doesn’t end there.
“Many patients have a lack of trust in the health care system,” he said. “There are also issues around underserved communities being able to afford quality care, so it’s important to keep time and financial burdens in mind when designing trials to help mitigate barriers such as travel, parking, time off work, and child care.”
Genentech started its diversity and inclusion effort several years ago. Dr. Freeman said that, until more trials become diverse, Black Americans will continue to pay the price. “I think they’re losing their lives in part due to lack of access to these trials. And that is why Genentech and all of us in the health care industry need to change how we design and enroll these studies. We have a long way to go, but I think the steps we’re taking are leading us in the right direction.”
Jennifer Jones-McMeans, PhD, director of global clinical affairs at Abbott Pharmaceuticals, is a clinical research scientist who has designed and led many clinical trials.
She said that Abbott is actively working on solutions.
“We have designed our trials to reduce the barriers to participation and expand access,” she said. “This can be as simple as providing transportation services or home visits for those who are housebound. We’re taking it a step further and providing home health services where someone comes to the home and provides follow-up visits there.”
They also provide interpretation services to address any language barriers.
“We are reaching out to a new set of talented investigators who work closely with underrepresented communities. They are very much wedded and supportive of the communities they treat. By working with doctors within these communities, it expands access to new therapies.”
Spokesperson Keanna Ghazvini said that Pfizer Pharmaceuticals is also committed to increasing minority participation in trials.
“We know that if historically underserved populations are left out of clinical trials, they risk not benefiting from medical breakthroughs down the line,” she said.
The National Institutes of Health’s National Library of Medicine maintains the clinicaltrials.gov database.
There, you can find information on nearly 372,000 publicly and privately supported clinical trials happening in all 50 states and 219 countries. Many are funded by the NIH, but not all of these studies have been evaluated by the U.S. government.
Andrea Denicoff, a nurse consultant at the National Cancer Institute and head of clinical trials operations for the NCI’s National Clinical Trials Network, has been involved in clinical research at the NIH for 35 years.
“It’s really important that our publicly funded trials represent the people of the country,” she said. “There are some cancers that we’re doing a good job in enrolling minorities, and other cancers we need to do a much better job in having a diverse representation in our trials.”
Ms. Denicoff believed opening trials in places where people live is key, but having a diverse clinical trials team is as important.
“We need to reinforce that cancer centers across the country have open doors, and anyone with cancer feels comfortable getting care at that center, and that also includes discussing the option to participate in clinical trials when one might be available. We know from research that when people are invited and asked about trial participation and educated about them, they’ll be much more interested in joining them.”
Ms. Denicoff said that, during the pandemic, the NCI quickly came up with guidance to allow trial sites to send patients their oral study drugs and set up virtual visits. She believes it may help increase future access.
‘Lola Fashoyin-Aje, MD, associate director for science and policy to address disparities in the Oncology Center of Excellence at the FDA, says the agency firmly believes clinical trials should represent the patients who will ultimately get the drug if it’s approved.
But the FDA’s power to require diversity in trials is limited.
“It is important to point out that there are legal constraints which limit’s FDA’s authority to require specific proportional representation in clinical trials by demographic factors,” Dr. Fashoyin-Aje said.
Still, some researchers feel the FDA should play a bigger role. The question is: Should diversity be mandated?
Rhonda Long is now back in Boston to start a new trial, with a new drug that targets her specific mutation. She will be there for 2 months. Once again, Lazarex will help cover some of the cost.
She wants people of color to understand that they are missing out on the promise of new cancer drugs and extended life.
“I feel like there’s not enough emphasis on clinical trials, I don’t believe there’s enough emphasis on second opinions, I don’t think there’s enough emphasis that medicine happens outside our borders, outside of our communities. Clinical trials that don’t have a broad range of participants, how do we know how effective they are if Black and brown people, Asian or Latin American people aren’t represented in the trial?”
And with more trials adopting virtual elements, she said it’s time for minorities to get on board.
Dr. Freedman believed the groundwork is being laid for that to happen. “I don’t think we’ll ever return back to the way we used to do things, where everything has to be done at the clinical trial site. I just don’t think we’re ever going back.”
A version of this article first appeared on WebMD.com.