User login
MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
Osimertinib/Savolitinib Combo Shows Promise in NSCLC
according to results of the phase 2 FLOWERS study.
Compared with EGFR inhibitor osimertinib alone, the combination demonstrated a clinically meaningful improvement in the objective response rate — the study’s primary endpoint — with a positive trend in progression-free survival and a manageable safety profile.
About 30% patients with EGFR-mutated NSCLC fail to respond well to EGFR–tyrosine kinase inhibitors (TKIs), explained Jin-Ji Yang, MD, with Guangdong Lung Cancer Institute, Guangzhou, China, who reported the study results at the annual meeting of the World Conference on Lung Cancer.
Data suggested that de novo MET amplification occurs in up to 5% patients with treatment-naive, EGFR-mutated advanced NSCLC, and MET overexpression occurs in up to 15% these patients.
Coexistence of EGFR mutation and MET amplification/overexpression reduces sensitivity to EGFR-TKI therapy “and is likely the mechanism for mediating primary resistance to first-line EGFR-TKI monotherapy,” Dr. Yang explained in her presentation.
Osimertinib is a third-generation EGFR-TKI recommended as the first-line treatment for EGFR-mutant advanced NSCLC. Savolitinib is a highly selective MET-TKI which has demonstrated antitumor activity in various cancers with MET alterations.
The FLOWERS study is the first to test whether combining the two agents could improve efficacy and overcome MET-driven primary resistance in these patients.
The phase 2 study enrolled 44 treatment-naive patients with de novo MET-aberrant, EGFR-mutant, stage IIIB-IV NSCLC; 23 were randomly allocated to receive oral osimertinib (80 mg once daily) alone and 21 to receive oral osimertinib (80 mg once daily) plus savolitinib (300 mg twice daily).
At a median follow-up of 8.2 months, the objective response rate was 60.9% with osimertinib monotherapy vs 90.5% with combination therapy. The disease control rate was also better with the combination therapy than with monotherapy (95.2% vs 87%).
Median duration of response (not yet mature) was 8.4 months with monotherapy vs 18.6 months with combination therapy.
Preliminary progression-free survival data also showed a trend in favor of combination therapy over monotherapy (a median of 19.3 vs 9.3 months; hazard ratio, 0.59).
Most treatment-related adverse events were grade 1 or 2, and there were no fatal adverse events.
Treatment-related adverse events of grade 3 or higher were more common with combination therapy (57.1% vs 8.7%). The most common events with monotherapy were diarrhea (56.5%), rash (52.2%), and pruritus (43.5%) and with dual therapy were rash (52.4%), thrombocytopenia (52.4%), and peripheral edema (42.9%).
The results showed that the combination therapy has the potential to become a first-line treatment option for patients who do not respond well to EGFR-TKIs alone, Dr. Yang said in a press release.
Discussant for the study Paul Paik, MD, thoracic oncologist at Memorial Sloan Kettering Cancer Center in New York City, said this study “adds to data suggesting high MET expression might be a poor prognostic or predictive marker, the outcomes of which are improved with MET inhibition.”
He cautioned, however, that there appears to be “quality of life, side-effect trade-offs with dual MET plus EGFR TKI upfront.”
Dr. Paik said he looks forward to results from FLOWERS on serial circulating tumor DNA and formal androgen receptor testing, which “might aid in further assessing clonality and characterizing MET as a co-driver in this setting.”
The study was funded by AstraZeneca China. Dr. Yang had no disclosures. Dr. Paik disclosed relationships with EMD Serono, Bicara, Novartis, and Summit.
A version of this article first appeared on Medscape.com.
according to results of the phase 2 FLOWERS study.
Compared with EGFR inhibitor osimertinib alone, the combination demonstrated a clinically meaningful improvement in the objective response rate — the study’s primary endpoint — with a positive trend in progression-free survival and a manageable safety profile.
About 30% patients with EGFR-mutated NSCLC fail to respond well to EGFR–tyrosine kinase inhibitors (TKIs), explained Jin-Ji Yang, MD, with Guangdong Lung Cancer Institute, Guangzhou, China, who reported the study results at the annual meeting of the World Conference on Lung Cancer.
Data suggested that de novo MET amplification occurs in up to 5% patients with treatment-naive, EGFR-mutated advanced NSCLC, and MET overexpression occurs in up to 15% these patients.
Coexistence of EGFR mutation and MET amplification/overexpression reduces sensitivity to EGFR-TKI therapy “and is likely the mechanism for mediating primary resistance to first-line EGFR-TKI monotherapy,” Dr. Yang explained in her presentation.
Osimertinib is a third-generation EGFR-TKI recommended as the first-line treatment for EGFR-mutant advanced NSCLC. Savolitinib is a highly selective MET-TKI which has demonstrated antitumor activity in various cancers with MET alterations.
The FLOWERS study is the first to test whether combining the two agents could improve efficacy and overcome MET-driven primary resistance in these patients.
The phase 2 study enrolled 44 treatment-naive patients with de novo MET-aberrant, EGFR-mutant, stage IIIB-IV NSCLC; 23 were randomly allocated to receive oral osimertinib (80 mg once daily) alone and 21 to receive oral osimertinib (80 mg once daily) plus savolitinib (300 mg twice daily).
At a median follow-up of 8.2 months, the objective response rate was 60.9% with osimertinib monotherapy vs 90.5% with combination therapy. The disease control rate was also better with the combination therapy than with monotherapy (95.2% vs 87%).
Median duration of response (not yet mature) was 8.4 months with monotherapy vs 18.6 months with combination therapy.
Preliminary progression-free survival data also showed a trend in favor of combination therapy over monotherapy (a median of 19.3 vs 9.3 months; hazard ratio, 0.59).
Most treatment-related adverse events were grade 1 or 2, and there were no fatal adverse events.
Treatment-related adverse events of grade 3 or higher were more common with combination therapy (57.1% vs 8.7%). The most common events with monotherapy were diarrhea (56.5%), rash (52.2%), and pruritus (43.5%) and with dual therapy were rash (52.4%), thrombocytopenia (52.4%), and peripheral edema (42.9%).
The results showed that the combination therapy has the potential to become a first-line treatment option for patients who do not respond well to EGFR-TKIs alone, Dr. Yang said in a press release.
Discussant for the study Paul Paik, MD, thoracic oncologist at Memorial Sloan Kettering Cancer Center in New York City, said this study “adds to data suggesting high MET expression might be a poor prognostic or predictive marker, the outcomes of which are improved with MET inhibition.”
He cautioned, however, that there appears to be “quality of life, side-effect trade-offs with dual MET plus EGFR TKI upfront.”
Dr. Paik said he looks forward to results from FLOWERS on serial circulating tumor DNA and formal androgen receptor testing, which “might aid in further assessing clonality and characterizing MET as a co-driver in this setting.”
The study was funded by AstraZeneca China. Dr. Yang had no disclosures. Dr. Paik disclosed relationships with EMD Serono, Bicara, Novartis, and Summit.
A version of this article first appeared on Medscape.com.
according to results of the phase 2 FLOWERS study.
Compared with EGFR inhibitor osimertinib alone, the combination demonstrated a clinically meaningful improvement in the objective response rate — the study’s primary endpoint — with a positive trend in progression-free survival and a manageable safety profile.
About 30% patients with EGFR-mutated NSCLC fail to respond well to EGFR–tyrosine kinase inhibitors (TKIs), explained Jin-Ji Yang, MD, with Guangdong Lung Cancer Institute, Guangzhou, China, who reported the study results at the annual meeting of the World Conference on Lung Cancer.
Data suggested that de novo MET amplification occurs in up to 5% patients with treatment-naive, EGFR-mutated advanced NSCLC, and MET overexpression occurs in up to 15% these patients.
Coexistence of EGFR mutation and MET amplification/overexpression reduces sensitivity to EGFR-TKI therapy “and is likely the mechanism for mediating primary resistance to first-line EGFR-TKI monotherapy,” Dr. Yang explained in her presentation.
Osimertinib is a third-generation EGFR-TKI recommended as the first-line treatment for EGFR-mutant advanced NSCLC. Savolitinib is a highly selective MET-TKI which has demonstrated antitumor activity in various cancers with MET alterations.
The FLOWERS study is the first to test whether combining the two agents could improve efficacy and overcome MET-driven primary resistance in these patients.
The phase 2 study enrolled 44 treatment-naive patients with de novo MET-aberrant, EGFR-mutant, stage IIIB-IV NSCLC; 23 were randomly allocated to receive oral osimertinib (80 mg once daily) alone and 21 to receive oral osimertinib (80 mg once daily) plus savolitinib (300 mg twice daily).
At a median follow-up of 8.2 months, the objective response rate was 60.9% with osimertinib monotherapy vs 90.5% with combination therapy. The disease control rate was also better with the combination therapy than with monotherapy (95.2% vs 87%).
Median duration of response (not yet mature) was 8.4 months with monotherapy vs 18.6 months with combination therapy.
Preliminary progression-free survival data also showed a trend in favor of combination therapy over monotherapy (a median of 19.3 vs 9.3 months; hazard ratio, 0.59).
Most treatment-related adverse events were grade 1 or 2, and there were no fatal adverse events.
Treatment-related adverse events of grade 3 or higher were more common with combination therapy (57.1% vs 8.7%). The most common events with monotherapy were diarrhea (56.5%), rash (52.2%), and pruritus (43.5%) and with dual therapy were rash (52.4%), thrombocytopenia (52.4%), and peripheral edema (42.9%).
The results showed that the combination therapy has the potential to become a first-line treatment option for patients who do not respond well to EGFR-TKIs alone, Dr. Yang said in a press release.
Discussant for the study Paul Paik, MD, thoracic oncologist at Memorial Sloan Kettering Cancer Center in New York City, said this study “adds to data suggesting high MET expression might be a poor prognostic or predictive marker, the outcomes of which are improved with MET inhibition.”
He cautioned, however, that there appears to be “quality of life, side-effect trade-offs with dual MET plus EGFR TKI upfront.”
Dr. Paik said he looks forward to results from FLOWERS on serial circulating tumor DNA and formal androgen receptor testing, which “might aid in further assessing clonality and characterizing MET as a co-driver in this setting.”
The study was funded by AstraZeneca China. Dr. Yang had no disclosures. Dr. Paik disclosed relationships with EMD Serono, Bicara, Novartis, and Summit.
A version of this article first appeared on Medscape.com.
FROM WCLC 2024
No Matched Sibling Donor? Sickle Cell Experts Debate Next-Best Option
“If there is an indication for intervention, for a curative therapy, in the absence of a matched sibling donor, gene therapy is the first choice,” Jaap-Jan Boelens, MD, PhD, of Memorial Sloan Kettering Cancer Center, New York City, argued in a presentation at the annual meeting of the Society of Hematologic Oncology (SOHO) in Houston.
“In the registries, alternative transplant outcomes are pretty poor, although there is some encouraging data coming up. The time is not there yet when this is the [best] choice.”
But Adetola Kassim, MBBS, of Vanderbilt University Medical Center in Nashville, Tennessee, said patients with sickle cell disease (SCD) who don’t qualify for a matched sibling donor transplant can still have good transplant options. And the results can be impressive.
“Once you’re engrafted, and you don’t lose your graft, the effect in transplant is lifelong,” he said. When it comes to long-lasting effects, he added, “we’re not sure yet about gene therapy.”
As Dr. Kassim noted, SCD continues to take a huge toll.
“Median survival for patients with sickle cell anemia remains stuck in the fifth decade of life with no change in 25 years,” he said. Heart, lung, and kidney complications account for 50% of identifiable causes of death, followed by about 26% attributed to cardiovascular disease, he said. “The question here is about which therapy can impact the most debilitating complication in children, which is stroke, and improve survival in adults with progressive organ dysfunction.”
Dr. Boelens said there are “huge barriers” to stem cell transplant in SCD because only 15% of patients eligible for the treatment have a matched related donor, and only 10% have a matched related or unrelated donor.
“There’s also a lack of financial and psychosocial support in many of the families. There is also parental refusal because of the mortality risk, and there’s also physician refusal because hematologists aren’t always in the same hospitals as the transplant programs.”
Dr. Boelens highlighted a 2019 study of data from 2008-2017 that found outcomes in unmatched donor transplantations are “not great,” with higher risk for mortality and graft failure.
As an alternative, he said, two gene therapies, both gene “additions,” are now approved by the US Food and Drug Administration (FDA). They are exagamglogene autotemcel (exa-cel, Casgevy) and betibeglogene autotemcel (LentiGlobin, Zynteglo). There’s also a gene “correction” option in the works, but it’s not yet ready for prime time, he said.
In the two approved gene therapy treatments, stem cells are removed from the patient, modified/manufactured in an outside facility, and then engrafted.
The advantages of gene therapy include no need to find a donor or worry about graft resistance, and there’s no need for immunosuppression, he said. However, the process takes a long time, there’s limited long-term data, and there’s a risk for loss of fertility and other chemotherapy-related adverse effects.
For his part, Dr. Kassim noted how several groups are excluded from the strong outcomes in matched sibling donor stem-cell transplants: Children with strokes and no eligible donors, others without eligible donors, and adults with severe disease and organ dysfunction who are typically excluded.
“We need transplants with less toxicity and alternative donors,” he said. Another challenge: “How do we decrease graft failure without increasing transplant-related mortality?”
Researchers are exploring several strategies to adjust drug therapy during conditioning, Dr. Kassim said, and he led a promising phase II study that explored one approach. The results of that study were recently published in the journal Blood. Graft failures were very low in both adults and children, he said, and 2-year survival among 70 patients was 94.8%. The five deaths were related to infection.
The evidence about the various strategies shows that “virtually all SCD patients, except those with severe heart, lung, or kidney disease” can benefit from a curative transplant, Dr. Kassim said.
Dr. Boelens had no disclosures. Disclosures for Dr. Kassim were not provided, but he recently reported no disclosures in a report about transplants in SCD.
A version of this article appeared on Medscape.com.
“If there is an indication for intervention, for a curative therapy, in the absence of a matched sibling donor, gene therapy is the first choice,” Jaap-Jan Boelens, MD, PhD, of Memorial Sloan Kettering Cancer Center, New York City, argued in a presentation at the annual meeting of the Society of Hematologic Oncology (SOHO) in Houston.
“In the registries, alternative transplant outcomes are pretty poor, although there is some encouraging data coming up. The time is not there yet when this is the [best] choice.”
But Adetola Kassim, MBBS, of Vanderbilt University Medical Center in Nashville, Tennessee, said patients with sickle cell disease (SCD) who don’t qualify for a matched sibling donor transplant can still have good transplant options. And the results can be impressive.
“Once you’re engrafted, and you don’t lose your graft, the effect in transplant is lifelong,” he said. When it comes to long-lasting effects, he added, “we’re not sure yet about gene therapy.”
As Dr. Kassim noted, SCD continues to take a huge toll.
“Median survival for patients with sickle cell anemia remains stuck in the fifth decade of life with no change in 25 years,” he said. Heart, lung, and kidney complications account for 50% of identifiable causes of death, followed by about 26% attributed to cardiovascular disease, he said. “The question here is about which therapy can impact the most debilitating complication in children, which is stroke, and improve survival in adults with progressive organ dysfunction.”
Dr. Boelens said there are “huge barriers” to stem cell transplant in SCD because only 15% of patients eligible for the treatment have a matched related donor, and only 10% have a matched related or unrelated donor.
“There’s also a lack of financial and psychosocial support in many of the families. There is also parental refusal because of the mortality risk, and there’s also physician refusal because hematologists aren’t always in the same hospitals as the transplant programs.”
Dr. Boelens highlighted a 2019 study of data from 2008-2017 that found outcomes in unmatched donor transplantations are “not great,” with higher risk for mortality and graft failure.
As an alternative, he said, two gene therapies, both gene “additions,” are now approved by the US Food and Drug Administration (FDA). They are exagamglogene autotemcel (exa-cel, Casgevy) and betibeglogene autotemcel (LentiGlobin, Zynteglo). There’s also a gene “correction” option in the works, but it’s not yet ready for prime time, he said.
In the two approved gene therapy treatments, stem cells are removed from the patient, modified/manufactured in an outside facility, and then engrafted.
The advantages of gene therapy include no need to find a donor or worry about graft resistance, and there’s no need for immunosuppression, he said. However, the process takes a long time, there’s limited long-term data, and there’s a risk for loss of fertility and other chemotherapy-related adverse effects.
For his part, Dr. Kassim noted how several groups are excluded from the strong outcomes in matched sibling donor stem-cell transplants: Children with strokes and no eligible donors, others without eligible donors, and adults with severe disease and organ dysfunction who are typically excluded.
“We need transplants with less toxicity and alternative donors,” he said. Another challenge: “How do we decrease graft failure without increasing transplant-related mortality?”
Researchers are exploring several strategies to adjust drug therapy during conditioning, Dr. Kassim said, and he led a promising phase II study that explored one approach. The results of that study were recently published in the journal Blood. Graft failures were very low in both adults and children, he said, and 2-year survival among 70 patients was 94.8%. The five deaths were related to infection.
The evidence about the various strategies shows that “virtually all SCD patients, except those with severe heart, lung, or kidney disease” can benefit from a curative transplant, Dr. Kassim said.
Dr. Boelens had no disclosures. Disclosures for Dr. Kassim were not provided, but he recently reported no disclosures in a report about transplants in SCD.
A version of this article appeared on Medscape.com.
“If there is an indication for intervention, for a curative therapy, in the absence of a matched sibling donor, gene therapy is the first choice,” Jaap-Jan Boelens, MD, PhD, of Memorial Sloan Kettering Cancer Center, New York City, argued in a presentation at the annual meeting of the Society of Hematologic Oncology (SOHO) in Houston.
“In the registries, alternative transplant outcomes are pretty poor, although there is some encouraging data coming up. The time is not there yet when this is the [best] choice.”
But Adetola Kassim, MBBS, of Vanderbilt University Medical Center in Nashville, Tennessee, said patients with sickle cell disease (SCD) who don’t qualify for a matched sibling donor transplant can still have good transplant options. And the results can be impressive.
“Once you’re engrafted, and you don’t lose your graft, the effect in transplant is lifelong,” he said. When it comes to long-lasting effects, he added, “we’re not sure yet about gene therapy.”
As Dr. Kassim noted, SCD continues to take a huge toll.
“Median survival for patients with sickle cell anemia remains stuck in the fifth decade of life with no change in 25 years,” he said. Heart, lung, and kidney complications account for 50% of identifiable causes of death, followed by about 26% attributed to cardiovascular disease, he said. “The question here is about which therapy can impact the most debilitating complication in children, which is stroke, and improve survival in adults with progressive organ dysfunction.”
Dr. Boelens said there are “huge barriers” to stem cell transplant in SCD because only 15% of patients eligible for the treatment have a matched related donor, and only 10% have a matched related or unrelated donor.
“There’s also a lack of financial and psychosocial support in many of the families. There is also parental refusal because of the mortality risk, and there’s also physician refusal because hematologists aren’t always in the same hospitals as the transplant programs.”
Dr. Boelens highlighted a 2019 study of data from 2008-2017 that found outcomes in unmatched donor transplantations are “not great,” with higher risk for mortality and graft failure.
As an alternative, he said, two gene therapies, both gene “additions,” are now approved by the US Food and Drug Administration (FDA). They are exagamglogene autotemcel (exa-cel, Casgevy) and betibeglogene autotemcel (LentiGlobin, Zynteglo). There’s also a gene “correction” option in the works, but it’s not yet ready for prime time, he said.
In the two approved gene therapy treatments, stem cells are removed from the patient, modified/manufactured in an outside facility, and then engrafted.
The advantages of gene therapy include no need to find a donor or worry about graft resistance, and there’s no need for immunosuppression, he said. However, the process takes a long time, there’s limited long-term data, and there’s a risk for loss of fertility and other chemotherapy-related adverse effects.
For his part, Dr. Kassim noted how several groups are excluded from the strong outcomes in matched sibling donor stem-cell transplants: Children with strokes and no eligible donors, others without eligible donors, and adults with severe disease and organ dysfunction who are typically excluded.
“We need transplants with less toxicity and alternative donors,” he said. Another challenge: “How do we decrease graft failure without increasing transplant-related mortality?”
Researchers are exploring several strategies to adjust drug therapy during conditioning, Dr. Kassim said, and he led a promising phase II study that explored one approach. The results of that study were recently published in the journal Blood. Graft failures were very low in both adults and children, he said, and 2-year survival among 70 patients was 94.8%. The five deaths were related to infection.
The evidence about the various strategies shows that “virtually all SCD patients, except those with severe heart, lung, or kidney disease” can benefit from a curative transplant, Dr. Kassim said.
Dr. Boelens had no disclosures. Disclosures for Dr. Kassim were not provided, but he recently reported no disclosures in a report about transplants in SCD.
A version of this article appeared on Medscape.com.
FROM SOHO 2024
SGLT2 Inhibitor Reduces Risk for Neurodegenerative Diseases in T2D
MADRID — Patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) show significant reductions in the risk of developing neurodegenerative disorders including Alzheimer’s disease, vascular dementia, and Parkinson’s disease, compared with those treated with other antidiabetic drugs, results from a large population-based cohort show.
“This was the largest nationwide population-based longitudinal cohort study to investigate the association between the use of SGLT2 inhibitors and the incidence of all-cause dementia and Parkinson’s disease,” said first author Hae Kyung Kim, MD, of the Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, in presenting the findings at the annual meeting of the European Association for the Study of Diabetes.
Type 2 diabetes is known to increase the risk for neurodegenerative diseases such as dementia or Alzheimer’s disease, said Dr. Kim. Key factors attributed to the risk include shared pathophysiological mechanisms such as central nervous system insulin resistance and reduced cerebral glucose metabolism.
While research is lacking on the role of antidiabetic drugs in the treatment of neurodegenerative diseases, the researcher noted that “SGLT2 inhibitors, which have shown significant cardiorenal benefits and enhanced energy metabolism through ketogenesis, offer promise.”
To further investigate, Dr. Kim and her colleagues conducted the retrospective study, evaluating data on more than 1.3 million enrollees in Korea’s National Health Insurance Service Database who were aged 40 years or older, diagnosed with type 2 diabetes, and had initiated antidiabetic drugs between September 2014 and December 2019.
In the propensity score analysis, 358,862 patients were matched 1:1, in groups of 179,431 participants each, based on whether they were treated with SGLT2is or other oral antidiabetic drugs. Patients with a history of neurodegenerative disease, cancer, or use of glucagon-like peptide 1 receptor agonists were excluded.
The patients had a mean age of 57.8 years, 57.9% were men, and 6837 had incident dementia or Parkinson’s disease events reported.
With a mean follow-up of 2.88 years, after adjustment for key variables, those treated with SGLT2is had a 19% reduced risk of developing Alzheimer’s disease (adjusted hazard ratio [aHR], 0.81), a 31% reduced risk for vascular dementia (aHR, 0.69), and a 20% reduced risk for Parkinson’s disease (aHR, 0.80) compared with the non-SGLT2i group.
Furthermore, those receiving SGLT2i treatment had a 21% reduced risk for all-cause dementia (aHR, 0.79) and a 22% reduced risk for all-cause dementia and Parkinson’s disease compared with the oral antidiabetic drug group (aHR, 0.78) with a 6-month drug use lag period.
The association was observed regardless of SGLT2i exposure duration. Subgroup analyses indicated that the reductions in neurodegenerative disorders among those receiving SGLT2is were not associated with factors including age, sex, body mass index, blood pressure, glucose, lipid profiles, kidney function, health behaviors, comorbidities, diabetic complications, or other medication use.
Dr. Kim speculated that mechanisms underlying the reduced dementia risk could include SGLT2i effects of mitigating the common severe risk factors of type 2 diabetes and neurodegenerative diseases, including hypertension, heart failure, and chronic kidney disease, and improving hyperperfusion in the heart and cerebral vascular insufficiency.
Commenting on the study to this news organization, Erik H. Serné, MD, of the VU University Medical Centre, Amsterdam, the Netherlands, who comoderated the session, noted that “people with type 2 diabetes have a 50%-100% increased risk of developing dementia, particularly Alzheimer’s disease and vascular dementia.”
“The increasing prevalence of both conditions poses significant public health challenges, highlighting the need for effective prevention strategies and interventions.”
Currently, treatments for dementia are limited, with most primarily addressing symptoms and not the underlying cause of the neurodegenerative disease, he said.
He noted that, in addition to the effects mentioned by Dr. Kim, SGLT2is are also speculated to provide potential neuroprotective effects through improved glycemic control and insulin sensitivity, reduced inflammation and oxidative stress, enhanced mitochondrial function and energy metabolism, and reduced beta-amyloid and tau pathology.
“These mechanisms collectively may reduce the risk of cognitive decline, particularly in diabetic patients, and warrant further investigation in clinical trials to solidify the neuroprotective role of SGLT2 inhibitors,” said Dr. Serné.
In addition to their benefits in type 2 diabetes, SGLT2is “now offer hope in the prevention of dementia, a disease that has very limited therapeutic options thus far. The current data [presented by Dr. Kim] seem to corroborate this,” he added.
Dr. Kim and Dr. Serné had no disclosures to report.
A version of this article first appeared on Medscape.com.
MADRID — Patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) show significant reductions in the risk of developing neurodegenerative disorders including Alzheimer’s disease, vascular dementia, and Parkinson’s disease, compared with those treated with other antidiabetic drugs, results from a large population-based cohort show.
“This was the largest nationwide population-based longitudinal cohort study to investigate the association between the use of SGLT2 inhibitors and the incidence of all-cause dementia and Parkinson’s disease,” said first author Hae Kyung Kim, MD, of the Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, in presenting the findings at the annual meeting of the European Association for the Study of Diabetes.
Type 2 diabetes is known to increase the risk for neurodegenerative diseases such as dementia or Alzheimer’s disease, said Dr. Kim. Key factors attributed to the risk include shared pathophysiological mechanisms such as central nervous system insulin resistance and reduced cerebral glucose metabolism.
While research is lacking on the role of antidiabetic drugs in the treatment of neurodegenerative diseases, the researcher noted that “SGLT2 inhibitors, which have shown significant cardiorenal benefits and enhanced energy metabolism through ketogenesis, offer promise.”
To further investigate, Dr. Kim and her colleagues conducted the retrospective study, evaluating data on more than 1.3 million enrollees in Korea’s National Health Insurance Service Database who were aged 40 years or older, diagnosed with type 2 diabetes, and had initiated antidiabetic drugs between September 2014 and December 2019.
In the propensity score analysis, 358,862 patients were matched 1:1, in groups of 179,431 participants each, based on whether they were treated with SGLT2is or other oral antidiabetic drugs. Patients with a history of neurodegenerative disease, cancer, or use of glucagon-like peptide 1 receptor agonists were excluded.
The patients had a mean age of 57.8 years, 57.9% were men, and 6837 had incident dementia or Parkinson’s disease events reported.
With a mean follow-up of 2.88 years, after adjustment for key variables, those treated with SGLT2is had a 19% reduced risk of developing Alzheimer’s disease (adjusted hazard ratio [aHR], 0.81), a 31% reduced risk for vascular dementia (aHR, 0.69), and a 20% reduced risk for Parkinson’s disease (aHR, 0.80) compared with the non-SGLT2i group.
Furthermore, those receiving SGLT2i treatment had a 21% reduced risk for all-cause dementia (aHR, 0.79) and a 22% reduced risk for all-cause dementia and Parkinson’s disease compared with the oral antidiabetic drug group (aHR, 0.78) with a 6-month drug use lag period.
The association was observed regardless of SGLT2i exposure duration. Subgroup analyses indicated that the reductions in neurodegenerative disorders among those receiving SGLT2is were not associated with factors including age, sex, body mass index, blood pressure, glucose, lipid profiles, kidney function, health behaviors, comorbidities, diabetic complications, or other medication use.
Dr. Kim speculated that mechanisms underlying the reduced dementia risk could include SGLT2i effects of mitigating the common severe risk factors of type 2 diabetes and neurodegenerative diseases, including hypertension, heart failure, and chronic kidney disease, and improving hyperperfusion in the heart and cerebral vascular insufficiency.
Commenting on the study to this news organization, Erik H. Serné, MD, of the VU University Medical Centre, Amsterdam, the Netherlands, who comoderated the session, noted that “people with type 2 diabetes have a 50%-100% increased risk of developing dementia, particularly Alzheimer’s disease and vascular dementia.”
“The increasing prevalence of both conditions poses significant public health challenges, highlighting the need for effective prevention strategies and interventions.”
Currently, treatments for dementia are limited, with most primarily addressing symptoms and not the underlying cause of the neurodegenerative disease, he said.
He noted that, in addition to the effects mentioned by Dr. Kim, SGLT2is are also speculated to provide potential neuroprotective effects through improved glycemic control and insulin sensitivity, reduced inflammation and oxidative stress, enhanced mitochondrial function and energy metabolism, and reduced beta-amyloid and tau pathology.
“These mechanisms collectively may reduce the risk of cognitive decline, particularly in diabetic patients, and warrant further investigation in clinical trials to solidify the neuroprotective role of SGLT2 inhibitors,” said Dr. Serné.
In addition to their benefits in type 2 diabetes, SGLT2is “now offer hope in the prevention of dementia, a disease that has very limited therapeutic options thus far. The current data [presented by Dr. Kim] seem to corroborate this,” he added.
Dr. Kim and Dr. Serné had no disclosures to report.
A version of this article first appeared on Medscape.com.
MADRID — Patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) show significant reductions in the risk of developing neurodegenerative disorders including Alzheimer’s disease, vascular dementia, and Parkinson’s disease, compared with those treated with other antidiabetic drugs, results from a large population-based cohort show.
“This was the largest nationwide population-based longitudinal cohort study to investigate the association between the use of SGLT2 inhibitors and the incidence of all-cause dementia and Parkinson’s disease,” said first author Hae Kyung Kim, MD, of the Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, in presenting the findings at the annual meeting of the European Association for the Study of Diabetes.
Type 2 diabetes is known to increase the risk for neurodegenerative diseases such as dementia or Alzheimer’s disease, said Dr. Kim. Key factors attributed to the risk include shared pathophysiological mechanisms such as central nervous system insulin resistance and reduced cerebral glucose metabolism.
While research is lacking on the role of antidiabetic drugs in the treatment of neurodegenerative diseases, the researcher noted that “SGLT2 inhibitors, which have shown significant cardiorenal benefits and enhanced energy metabolism through ketogenesis, offer promise.”
To further investigate, Dr. Kim and her colleagues conducted the retrospective study, evaluating data on more than 1.3 million enrollees in Korea’s National Health Insurance Service Database who were aged 40 years or older, diagnosed with type 2 diabetes, and had initiated antidiabetic drugs between September 2014 and December 2019.
In the propensity score analysis, 358,862 patients were matched 1:1, in groups of 179,431 participants each, based on whether they were treated with SGLT2is or other oral antidiabetic drugs. Patients with a history of neurodegenerative disease, cancer, or use of glucagon-like peptide 1 receptor agonists were excluded.
The patients had a mean age of 57.8 years, 57.9% were men, and 6837 had incident dementia or Parkinson’s disease events reported.
With a mean follow-up of 2.88 years, after adjustment for key variables, those treated with SGLT2is had a 19% reduced risk of developing Alzheimer’s disease (adjusted hazard ratio [aHR], 0.81), a 31% reduced risk for vascular dementia (aHR, 0.69), and a 20% reduced risk for Parkinson’s disease (aHR, 0.80) compared with the non-SGLT2i group.
Furthermore, those receiving SGLT2i treatment had a 21% reduced risk for all-cause dementia (aHR, 0.79) and a 22% reduced risk for all-cause dementia and Parkinson’s disease compared with the oral antidiabetic drug group (aHR, 0.78) with a 6-month drug use lag period.
The association was observed regardless of SGLT2i exposure duration. Subgroup analyses indicated that the reductions in neurodegenerative disorders among those receiving SGLT2is were not associated with factors including age, sex, body mass index, blood pressure, glucose, lipid profiles, kidney function, health behaviors, comorbidities, diabetic complications, or other medication use.
Dr. Kim speculated that mechanisms underlying the reduced dementia risk could include SGLT2i effects of mitigating the common severe risk factors of type 2 diabetes and neurodegenerative diseases, including hypertension, heart failure, and chronic kidney disease, and improving hyperperfusion in the heart and cerebral vascular insufficiency.
Commenting on the study to this news organization, Erik H. Serné, MD, of the VU University Medical Centre, Amsterdam, the Netherlands, who comoderated the session, noted that “people with type 2 diabetes have a 50%-100% increased risk of developing dementia, particularly Alzheimer’s disease and vascular dementia.”
“The increasing prevalence of both conditions poses significant public health challenges, highlighting the need for effective prevention strategies and interventions.”
Currently, treatments for dementia are limited, with most primarily addressing symptoms and not the underlying cause of the neurodegenerative disease, he said.
He noted that, in addition to the effects mentioned by Dr. Kim, SGLT2is are also speculated to provide potential neuroprotective effects through improved glycemic control and insulin sensitivity, reduced inflammation and oxidative stress, enhanced mitochondrial function and energy metabolism, and reduced beta-amyloid and tau pathology.
“These mechanisms collectively may reduce the risk of cognitive decline, particularly in diabetic patients, and warrant further investigation in clinical trials to solidify the neuroprotective role of SGLT2 inhibitors,” said Dr. Serné.
In addition to their benefits in type 2 diabetes, SGLT2is “now offer hope in the prevention of dementia, a disease that has very limited therapeutic options thus far. The current data [presented by Dr. Kim] seem to corroborate this,” he added.
Dr. Kim and Dr. Serné had no disclosures to report.
A version of this article first appeared on Medscape.com.
FROM EASD 2024
NSAIDs Offer No Relief for Pain From IUD Placement
Research on pain management during placement of intrauterine devices (IUD) is lacking, but most studies so far indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) are not effective, according to a poster presented at Pain Week 2024 in Las Vegas.
Roughly 79% of the 14 studies included in the systematic review found NSAIDs — one of the most common drugs clinicians advise patients to take before placement — did not diminish discomfort.
“We’re challenging the current practice of using just NSAIDs as a first-line of treatment,” said Kevin Rowland, PhD, professor and chair of biomedical sciences at Tilman J. Fertitta Family College of Medicine in Houston, who helped conduct the meta-analysis. “We need additional measures.”
Some studies found the drugs offered virtually no improvement for patients, while the biggest drop in pain shown in one study was about 40%. The range of pain levels women reported while using NSAIDs was between 1.8 and 7.3 on the visual analog scale (VAS), with an average score of 4.25.
The review included 10 types of NSAIDs and dosages administered to patients before the procedure. One intramuscular NSAID was included while the remaining were oral. All studies were peer-reviewed, used the VAS pain scale, and were not limited to any specific population.
The findings highlight a longstanding but unresolved problem in reproductive health: An overall lack of effective pain management strategies for gynecologic procedures.
“We went into this having a pretty good idea of what we were going to find because [the lack of NSAID efficacy] has been shown before, it’s been talked about before, and we’re just not listening as a medical community,” said Isabella D. Martingano, an MD candidate at Tilman J. Fertitta Family College of Medicine, who led the review.
The research also points to a lack of robust studies on pain during IUD placement, said Emma Lakey, a coauthor and medical student at Tilman J. Fertitta Family College of Medicine.
“We were only able to review 14 studies, which was enough to go off of, but considering we were looking for trials about pain control for a procedure that helps prevent pregnancy, that’s just not enough research,” Ms. Lakey said.
Discomfort associated with IUD placement ranges from mild to severe, can last for over a week, and includes cramping, bleeding, lightheadedness, nausea, and fainting. Some research suggests that providers may underestimate the level of pain the procedures cause.
“Unfortunately, the pain associated with IUD insertion and removal has been underplayed for a long time and many practitioners in the field likely haven’t counseled patients fully on what the procedure will feel like,” said Jennifer Chin, MD, an ob.gyn. and assistant professor of obstetrics and gynecology at the University of Washington in Seattle.
NSAIDs are not mentioned in the recently expanded guidelines on IUD placement from the US Centers for Disease Control and Prevention (CDC). The CDC recommends lidocaine paracervical blocks, gels, sprays, and creams, plus counseling women about pain ahead of the procedures.
IUDs are one of the most effective forms of birth control, with a failure rate below 1%.
Yet hearing about painful placement keeps many women from seeking out an IUD or replacing an existing device, Dr. Rowland said. The review adds to the body of evidence that current strategies are not working and that more research is needed, he said.
According to Dr. Chin, making IUDs more accessible means taking a more personalized approach to pain management while understanding that what may be a painless procedure for one patient may be excruciating for another.
Dr. Chin offers a range of options for her patients, including NSAIDs, lorazepam for anxiety, paracervical blocks, lidocaine jelly and spray, intravenous sedation, and general anesthesia. She also talks to her patients through the procedure and provides guided imagery and meditation.
“We should always make sure we’re prioritizing the patients and providing evidence-based, compassionate, and individualized care,” said Dr. Chin. “Each patient comes to us in a particular context and with a specific set of experiences and history that will make a difference in how we’re best able to take care of them.”
The authors reported no disclosures and no sources of funding. Dr. Chin reported no disclosures.
A version of this article first appeared on Medscape.com.
Research on pain management during placement of intrauterine devices (IUD) is lacking, but most studies so far indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) are not effective, according to a poster presented at Pain Week 2024 in Las Vegas.
Roughly 79% of the 14 studies included in the systematic review found NSAIDs — one of the most common drugs clinicians advise patients to take before placement — did not diminish discomfort.
“We’re challenging the current practice of using just NSAIDs as a first-line of treatment,” said Kevin Rowland, PhD, professor and chair of biomedical sciences at Tilman J. Fertitta Family College of Medicine in Houston, who helped conduct the meta-analysis. “We need additional measures.”
Some studies found the drugs offered virtually no improvement for patients, while the biggest drop in pain shown in one study was about 40%. The range of pain levels women reported while using NSAIDs was between 1.8 and 7.3 on the visual analog scale (VAS), with an average score of 4.25.
The review included 10 types of NSAIDs and dosages administered to patients before the procedure. One intramuscular NSAID was included while the remaining were oral. All studies were peer-reviewed, used the VAS pain scale, and were not limited to any specific population.
The findings highlight a longstanding but unresolved problem in reproductive health: An overall lack of effective pain management strategies for gynecologic procedures.
“We went into this having a pretty good idea of what we were going to find because [the lack of NSAID efficacy] has been shown before, it’s been talked about before, and we’re just not listening as a medical community,” said Isabella D. Martingano, an MD candidate at Tilman J. Fertitta Family College of Medicine, who led the review.
The research also points to a lack of robust studies on pain during IUD placement, said Emma Lakey, a coauthor and medical student at Tilman J. Fertitta Family College of Medicine.
“We were only able to review 14 studies, which was enough to go off of, but considering we were looking for trials about pain control for a procedure that helps prevent pregnancy, that’s just not enough research,” Ms. Lakey said.
Discomfort associated with IUD placement ranges from mild to severe, can last for over a week, and includes cramping, bleeding, lightheadedness, nausea, and fainting. Some research suggests that providers may underestimate the level of pain the procedures cause.
“Unfortunately, the pain associated with IUD insertion and removal has been underplayed for a long time and many practitioners in the field likely haven’t counseled patients fully on what the procedure will feel like,” said Jennifer Chin, MD, an ob.gyn. and assistant professor of obstetrics and gynecology at the University of Washington in Seattle.
NSAIDs are not mentioned in the recently expanded guidelines on IUD placement from the US Centers for Disease Control and Prevention (CDC). The CDC recommends lidocaine paracervical blocks, gels, sprays, and creams, plus counseling women about pain ahead of the procedures.
IUDs are one of the most effective forms of birth control, with a failure rate below 1%.
Yet hearing about painful placement keeps many women from seeking out an IUD or replacing an existing device, Dr. Rowland said. The review adds to the body of evidence that current strategies are not working and that more research is needed, he said.
According to Dr. Chin, making IUDs more accessible means taking a more personalized approach to pain management while understanding that what may be a painless procedure for one patient may be excruciating for another.
Dr. Chin offers a range of options for her patients, including NSAIDs, lorazepam for anxiety, paracervical blocks, lidocaine jelly and spray, intravenous sedation, and general anesthesia. She also talks to her patients through the procedure and provides guided imagery and meditation.
“We should always make sure we’re prioritizing the patients and providing evidence-based, compassionate, and individualized care,” said Dr. Chin. “Each patient comes to us in a particular context and with a specific set of experiences and history that will make a difference in how we’re best able to take care of them.”
The authors reported no disclosures and no sources of funding. Dr. Chin reported no disclosures.
A version of this article first appeared on Medscape.com.
Research on pain management during placement of intrauterine devices (IUD) is lacking, but most studies so far indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) are not effective, according to a poster presented at Pain Week 2024 in Las Vegas.
Roughly 79% of the 14 studies included in the systematic review found NSAIDs — one of the most common drugs clinicians advise patients to take before placement — did not diminish discomfort.
“We’re challenging the current practice of using just NSAIDs as a first-line of treatment,” said Kevin Rowland, PhD, professor and chair of biomedical sciences at Tilman J. Fertitta Family College of Medicine in Houston, who helped conduct the meta-analysis. “We need additional measures.”
Some studies found the drugs offered virtually no improvement for patients, while the biggest drop in pain shown in one study was about 40%. The range of pain levels women reported while using NSAIDs was between 1.8 and 7.3 on the visual analog scale (VAS), with an average score of 4.25.
The review included 10 types of NSAIDs and dosages administered to patients before the procedure. One intramuscular NSAID was included while the remaining were oral. All studies were peer-reviewed, used the VAS pain scale, and were not limited to any specific population.
The findings highlight a longstanding but unresolved problem in reproductive health: An overall lack of effective pain management strategies for gynecologic procedures.
“We went into this having a pretty good idea of what we were going to find because [the lack of NSAID efficacy] has been shown before, it’s been talked about before, and we’re just not listening as a medical community,” said Isabella D. Martingano, an MD candidate at Tilman J. Fertitta Family College of Medicine, who led the review.
The research also points to a lack of robust studies on pain during IUD placement, said Emma Lakey, a coauthor and medical student at Tilman J. Fertitta Family College of Medicine.
“We were only able to review 14 studies, which was enough to go off of, but considering we were looking for trials about pain control for a procedure that helps prevent pregnancy, that’s just not enough research,” Ms. Lakey said.
Discomfort associated with IUD placement ranges from mild to severe, can last for over a week, and includes cramping, bleeding, lightheadedness, nausea, and fainting. Some research suggests that providers may underestimate the level of pain the procedures cause.
“Unfortunately, the pain associated with IUD insertion and removal has been underplayed for a long time and many practitioners in the field likely haven’t counseled patients fully on what the procedure will feel like,” said Jennifer Chin, MD, an ob.gyn. and assistant professor of obstetrics and gynecology at the University of Washington in Seattle.
NSAIDs are not mentioned in the recently expanded guidelines on IUD placement from the US Centers for Disease Control and Prevention (CDC). The CDC recommends lidocaine paracervical blocks, gels, sprays, and creams, plus counseling women about pain ahead of the procedures.
IUDs are one of the most effective forms of birth control, with a failure rate below 1%.
Yet hearing about painful placement keeps many women from seeking out an IUD or replacing an existing device, Dr. Rowland said. The review adds to the body of evidence that current strategies are not working and that more research is needed, he said.
According to Dr. Chin, making IUDs more accessible means taking a more personalized approach to pain management while understanding that what may be a painless procedure for one patient may be excruciating for another.
Dr. Chin offers a range of options for her patients, including NSAIDs, lorazepam for anxiety, paracervical blocks, lidocaine jelly and spray, intravenous sedation, and general anesthesia. She also talks to her patients through the procedure and provides guided imagery and meditation.
“We should always make sure we’re prioritizing the patients and providing evidence-based, compassionate, and individualized care,” said Dr. Chin. “Each patient comes to us in a particular context and with a specific set of experiences and history that will make a difference in how we’re best able to take care of them.”
The authors reported no disclosures and no sources of funding. Dr. Chin reported no disclosures.
A version of this article first appeared on Medscape.com.
Early vs Late Fast Window: Is One More Effective?
MADRID — A daily 8-hour eating window controls blood glucose whether followed early or late in the day by people at risk for type 2 diabetes, showed a time-restricted eating (TRE) study presented at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.
The study, examining shifting the time of day for the 8-hour eating window along with a tightly controlled diet, found that 8 hours of TRE — whether early or late in the day — led to a significant improvement in the time spent within a normal daily blood glucose range and in glycemic variability.
“We didn’t show a benefit in terms of early versus late TRE, but we did show a benefit of time-restricted eating within a window of 8 h/d,” said study lead Kelly Bowden Davies, MSc, PhD, from Manchester Metropolitan University, Manchester, England, when presenting the work. “It doesn’t matter when you restrict eating, but if you restrict it to 8 hours then, according to our study, it benefits glycemic control in people at risk of type 2 diabetes.”
The researcher added that the effect was seen after only 3 days, and “demonstrates its therapeutic role in adults at risk of type 2 diabetes, which warrants investigation in the longer term.”
The current study examined the effect of shifting the time of day for the TRE window from early (8 AM-4 PM) to late (12 PM-8 PM) in people at risk of developing type 2 diabetes due to a lifestyle characterized as sedentary and poor diet.
Previous studies indicate that TRE, which limits when, but not what, individuals eat, can improve insulin sensitivity and A1c in people at risk for type 2 diabetes.
But Dr. Bowden Davies pointed out that the effect of TRE on glycemic variability remained unclear. While prior work had attributed the positive effects of TRE to reduced energy intake, this study provided a diet where energy consumption matched energy expenditure — taking into account sex, age, weight, height, and activity level, termed a “eucaloric” diet.
“Some research groups recognize that if we manipulate the time at which we eat, then we can better align with circadian metabolic rhythms to improve whole body insulin sensitivity and glycemic variability,” explained Dr. Bowden Davies. “It may be that eating in the morning may be better aligned [with circadian rhythms] and cause greater improvement in glucose control.”
Three-Day TRE Plan Led to Blood Glucose Control
In a cross-over study design, all 15 participants were randomized to follow the early and late TRE regimens with a 7-day washout period in the middle. Participants had a mean body mass index (BMI) of 27.7 kg/m2, had a mean waist circumference of 73 cm, were sedentary, and followed a poor diet.
“Participants were normoglycemic so had good glucose control, but due to having overweight and obesity, they are considered as having risk factors for the development of type 2 diabetes,” noted Dr. Bowden Davies.
Before the TRE period, participants provided researchers with a dietary record. If they started on the early TRE, they crossed over to the late TRE after the washout period, and vice versa, she explained.
Continuous glucose monitoring (FreeStyle Libre 2, Abbott Laboratories) was carried out across the study to assess the daily time spent in euglycemia (3.9-7.8 mmol/L) and provide markers of glycemic variability, including mean absolute glucose, coefficient of variation, and mean amplitude of glucose excursions. Blood draws both pre- and post-TRE period provided biochemical measurements, and anthropometric readings were also taken.
There were nine female participants, with a mean age of 52 years, a BMI of 28 kg/m2, and an A1c level of 37.9 mmol/mol (5.6%). They tended to snack across an eating period of 14 h/d or more (habitual eating). They were assigned to two different investigational eating patterns for 3-day durations: Early or late, and these findings were compared with those from participants who continued their habitual eating.
Participants were provided with a eucaloric, standardized diet [50% carbohydrates, 30% fat, and 20% protein] to be eaten during the TRE period, whereas they ate as usual (ie, as and what they wanted) when not on the TRE regimen.
No changes were seen in the biochemistry markers assessed. “Given they only followed the TRE for 3 days, this is unsurprising,” remarked Dr. Bowden Davies. “We did see weight loss after only 3 days of TRE of around 1.1 kg across the two interventions,” she reported.
Referring to the early vs late TRE regimen, she added that “we didn’t see a benefit [no significant differences in glycemic control] of early compared with late TRE, but we did see a benefit of restricting the eating window to 8 h/d, so both conditions [early and late TRE regimens] had a benefit on glucose control.”
Variables of blood glucose control were also reduced while on the TRE regimen compared with habitual eating (more than 14 h/d), with significantly increased time spent within the normal blood glucose range on average by 3.3%, and also reduced mean absolute glucose by 0.6 mmol/L, coefficient of variation by 2.6%, and mean amplitude of glucose excursions by 0.4 mmol/L.
“Within 3 days, this is quite striking,” Dr. Bowden Davies pointed out.
She added that these data were interim analyses, but “these are positive in terms of participants seeing a benefit in glucose control and glycemic variability, which is a risk factor for developing type 2 diabetes but also for microvascular complications. We also saw improved time in range in terms of tight glucose control.
“Even in 3 days, there were small, subtle differences which are subclinical — but this is not a clinical cohort. The results are statistically significant and a promising piece of data to suggest a feasible intervention that could be translated across different populations,” she said, adding that over a longer time period, changes between TRE timing might show changes in people at risk for type 2 diabetes who don’t have compromised circadian rhythms.
Moderating the session was Lutgarda Bozzetto, MD, from the University of Naples Federico II, Naples, Italy. She told this news organization, “It’s a hot topic right now, and the finding that there’s no difference in the time of day when the restricted eating is done suggests that in people at risk of diabetes, the hormonal flux and cycle involved in blood glucose control is not so strong or sensitive.”
Using a continuous glucose monitor, they can look at their blood glucose levels after eating, and this might “be powerful in guiding behavioral change,” said Dr. Bozzetto.
Abbott Laboratories funded the continuous glucose monitoring. Neither Dr. Bowden Davies nor Dr. Bozzetto had any other relevant financial disclosures.
A version of this article first appeared on Medscape.com.
MADRID — A daily 8-hour eating window controls blood glucose whether followed early or late in the day by people at risk for type 2 diabetes, showed a time-restricted eating (TRE) study presented at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.
The study, examining shifting the time of day for the 8-hour eating window along with a tightly controlled diet, found that 8 hours of TRE — whether early or late in the day — led to a significant improvement in the time spent within a normal daily blood glucose range and in glycemic variability.
“We didn’t show a benefit in terms of early versus late TRE, but we did show a benefit of time-restricted eating within a window of 8 h/d,” said study lead Kelly Bowden Davies, MSc, PhD, from Manchester Metropolitan University, Manchester, England, when presenting the work. “It doesn’t matter when you restrict eating, but if you restrict it to 8 hours then, according to our study, it benefits glycemic control in people at risk of type 2 diabetes.”
The researcher added that the effect was seen after only 3 days, and “demonstrates its therapeutic role in adults at risk of type 2 diabetes, which warrants investigation in the longer term.”
The current study examined the effect of shifting the time of day for the TRE window from early (8 AM-4 PM) to late (12 PM-8 PM) in people at risk of developing type 2 diabetes due to a lifestyle characterized as sedentary and poor diet.
Previous studies indicate that TRE, which limits when, but not what, individuals eat, can improve insulin sensitivity and A1c in people at risk for type 2 diabetes.
But Dr. Bowden Davies pointed out that the effect of TRE on glycemic variability remained unclear. While prior work had attributed the positive effects of TRE to reduced energy intake, this study provided a diet where energy consumption matched energy expenditure — taking into account sex, age, weight, height, and activity level, termed a “eucaloric” diet.
“Some research groups recognize that if we manipulate the time at which we eat, then we can better align with circadian metabolic rhythms to improve whole body insulin sensitivity and glycemic variability,” explained Dr. Bowden Davies. “It may be that eating in the morning may be better aligned [with circadian rhythms] and cause greater improvement in glucose control.”
Three-Day TRE Plan Led to Blood Glucose Control
In a cross-over study design, all 15 participants were randomized to follow the early and late TRE regimens with a 7-day washout period in the middle. Participants had a mean body mass index (BMI) of 27.7 kg/m2, had a mean waist circumference of 73 cm, were sedentary, and followed a poor diet.
“Participants were normoglycemic so had good glucose control, but due to having overweight and obesity, they are considered as having risk factors for the development of type 2 diabetes,” noted Dr. Bowden Davies.
Before the TRE period, participants provided researchers with a dietary record. If they started on the early TRE, they crossed over to the late TRE after the washout period, and vice versa, she explained.
Continuous glucose monitoring (FreeStyle Libre 2, Abbott Laboratories) was carried out across the study to assess the daily time spent in euglycemia (3.9-7.8 mmol/L) and provide markers of glycemic variability, including mean absolute glucose, coefficient of variation, and mean amplitude of glucose excursions. Blood draws both pre- and post-TRE period provided biochemical measurements, and anthropometric readings were also taken.
There were nine female participants, with a mean age of 52 years, a BMI of 28 kg/m2, and an A1c level of 37.9 mmol/mol (5.6%). They tended to snack across an eating period of 14 h/d or more (habitual eating). They were assigned to two different investigational eating patterns for 3-day durations: Early or late, and these findings were compared with those from participants who continued their habitual eating.
Participants were provided with a eucaloric, standardized diet [50% carbohydrates, 30% fat, and 20% protein] to be eaten during the TRE period, whereas they ate as usual (ie, as and what they wanted) when not on the TRE regimen.
No changes were seen in the biochemistry markers assessed. “Given they only followed the TRE for 3 days, this is unsurprising,” remarked Dr. Bowden Davies. “We did see weight loss after only 3 days of TRE of around 1.1 kg across the two interventions,” she reported.
Referring to the early vs late TRE regimen, she added that “we didn’t see a benefit [no significant differences in glycemic control] of early compared with late TRE, but we did see a benefit of restricting the eating window to 8 h/d, so both conditions [early and late TRE regimens] had a benefit on glucose control.”
Variables of blood glucose control were also reduced while on the TRE regimen compared with habitual eating (more than 14 h/d), with significantly increased time spent within the normal blood glucose range on average by 3.3%, and also reduced mean absolute glucose by 0.6 mmol/L, coefficient of variation by 2.6%, and mean amplitude of glucose excursions by 0.4 mmol/L.
“Within 3 days, this is quite striking,” Dr. Bowden Davies pointed out.
She added that these data were interim analyses, but “these are positive in terms of participants seeing a benefit in glucose control and glycemic variability, which is a risk factor for developing type 2 diabetes but also for microvascular complications. We also saw improved time in range in terms of tight glucose control.
“Even in 3 days, there were small, subtle differences which are subclinical — but this is not a clinical cohort. The results are statistically significant and a promising piece of data to suggest a feasible intervention that could be translated across different populations,” she said, adding that over a longer time period, changes between TRE timing might show changes in people at risk for type 2 diabetes who don’t have compromised circadian rhythms.
Moderating the session was Lutgarda Bozzetto, MD, from the University of Naples Federico II, Naples, Italy. She told this news organization, “It’s a hot topic right now, and the finding that there’s no difference in the time of day when the restricted eating is done suggests that in people at risk of diabetes, the hormonal flux and cycle involved in blood glucose control is not so strong or sensitive.”
Using a continuous glucose monitor, they can look at their blood glucose levels after eating, and this might “be powerful in guiding behavioral change,” said Dr. Bozzetto.
Abbott Laboratories funded the continuous glucose monitoring. Neither Dr. Bowden Davies nor Dr. Bozzetto had any other relevant financial disclosures.
A version of this article first appeared on Medscape.com.
MADRID — A daily 8-hour eating window controls blood glucose whether followed early or late in the day by people at risk for type 2 diabetes, showed a time-restricted eating (TRE) study presented at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.
The study, examining shifting the time of day for the 8-hour eating window along with a tightly controlled diet, found that 8 hours of TRE — whether early or late in the day — led to a significant improvement in the time spent within a normal daily blood glucose range and in glycemic variability.
“We didn’t show a benefit in terms of early versus late TRE, but we did show a benefit of time-restricted eating within a window of 8 h/d,” said study lead Kelly Bowden Davies, MSc, PhD, from Manchester Metropolitan University, Manchester, England, when presenting the work. “It doesn’t matter when you restrict eating, but if you restrict it to 8 hours then, according to our study, it benefits glycemic control in people at risk of type 2 diabetes.”
The researcher added that the effect was seen after only 3 days, and “demonstrates its therapeutic role in adults at risk of type 2 diabetes, which warrants investigation in the longer term.”
The current study examined the effect of shifting the time of day for the TRE window from early (8 AM-4 PM) to late (12 PM-8 PM) in people at risk of developing type 2 diabetes due to a lifestyle characterized as sedentary and poor diet.
Previous studies indicate that TRE, which limits when, but not what, individuals eat, can improve insulin sensitivity and A1c in people at risk for type 2 diabetes.
But Dr. Bowden Davies pointed out that the effect of TRE on glycemic variability remained unclear. While prior work had attributed the positive effects of TRE to reduced energy intake, this study provided a diet where energy consumption matched energy expenditure — taking into account sex, age, weight, height, and activity level, termed a “eucaloric” diet.
“Some research groups recognize that if we manipulate the time at which we eat, then we can better align with circadian metabolic rhythms to improve whole body insulin sensitivity and glycemic variability,” explained Dr. Bowden Davies. “It may be that eating in the morning may be better aligned [with circadian rhythms] and cause greater improvement in glucose control.”
Three-Day TRE Plan Led to Blood Glucose Control
In a cross-over study design, all 15 participants were randomized to follow the early and late TRE regimens with a 7-day washout period in the middle. Participants had a mean body mass index (BMI) of 27.7 kg/m2, had a mean waist circumference of 73 cm, were sedentary, and followed a poor diet.
“Participants were normoglycemic so had good glucose control, but due to having overweight and obesity, they are considered as having risk factors for the development of type 2 diabetes,” noted Dr. Bowden Davies.
Before the TRE period, participants provided researchers with a dietary record. If they started on the early TRE, they crossed over to the late TRE after the washout period, and vice versa, she explained.
Continuous glucose monitoring (FreeStyle Libre 2, Abbott Laboratories) was carried out across the study to assess the daily time spent in euglycemia (3.9-7.8 mmol/L) and provide markers of glycemic variability, including mean absolute glucose, coefficient of variation, and mean amplitude of glucose excursions. Blood draws both pre- and post-TRE period provided biochemical measurements, and anthropometric readings were also taken.
There were nine female participants, with a mean age of 52 years, a BMI of 28 kg/m2, and an A1c level of 37.9 mmol/mol (5.6%). They tended to snack across an eating period of 14 h/d or more (habitual eating). They were assigned to two different investigational eating patterns for 3-day durations: Early or late, and these findings were compared with those from participants who continued their habitual eating.
Participants were provided with a eucaloric, standardized diet [50% carbohydrates, 30% fat, and 20% protein] to be eaten during the TRE period, whereas they ate as usual (ie, as and what they wanted) when not on the TRE regimen.
No changes were seen in the biochemistry markers assessed. “Given they only followed the TRE for 3 days, this is unsurprising,” remarked Dr. Bowden Davies. “We did see weight loss after only 3 days of TRE of around 1.1 kg across the two interventions,” she reported.
Referring to the early vs late TRE regimen, she added that “we didn’t see a benefit [no significant differences in glycemic control] of early compared with late TRE, but we did see a benefit of restricting the eating window to 8 h/d, so both conditions [early and late TRE regimens] had a benefit on glucose control.”
Variables of blood glucose control were also reduced while on the TRE regimen compared with habitual eating (more than 14 h/d), with significantly increased time spent within the normal blood glucose range on average by 3.3%, and also reduced mean absolute glucose by 0.6 mmol/L, coefficient of variation by 2.6%, and mean amplitude of glucose excursions by 0.4 mmol/L.
“Within 3 days, this is quite striking,” Dr. Bowden Davies pointed out.
She added that these data were interim analyses, but “these are positive in terms of participants seeing a benefit in glucose control and glycemic variability, which is a risk factor for developing type 2 diabetes but also for microvascular complications. We also saw improved time in range in terms of tight glucose control.
“Even in 3 days, there were small, subtle differences which are subclinical — but this is not a clinical cohort. The results are statistically significant and a promising piece of data to suggest a feasible intervention that could be translated across different populations,” she said, adding that over a longer time period, changes between TRE timing might show changes in people at risk for type 2 diabetes who don’t have compromised circadian rhythms.
Moderating the session was Lutgarda Bozzetto, MD, from the University of Naples Federico II, Naples, Italy. She told this news organization, “It’s a hot topic right now, and the finding that there’s no difference in the time of day when the restricted eating is done suggests that in people at risk of diabetes, the hormonal flux and cycle involved in blood glucose control is not so strong or sensitive.”
Using a continuous glucose monitor, they can look at their blood glucose levels after eating, and this might “be powerful in guiding behavioral change,” said Dr. Bozzetto.
Abbott Laboratories funded the continuous glucose monitoring. Neither Dr. Bowden Davies nor Dr. Bozzetto had any other relevant financial disclosures.
A version of this article first appeared on Medscape.com.
FROM EASD 2024
Treatment Options in MCL: What Are the Best Practices?
In the frontline setting, findings suggest that regimens should differ significantly on the basis of whether patients are older or younger, whereas more data are needed to understand whether treatment can overcome poor prognoses in patients with TP53 mutations, lymphoma specialist Nina Wagner-Johnston, MD, of Johns Hopkins University School of Medicine, Baltimore, said in a presentation at the annual meeting of the Society of Hematologic Oncology (SOHO) 2024 in Houston, Texas.
On the relapsed/refractory front, patients need better options after treatment with Bruton tyrosine kinase inhibitors or chimeric antigen receptor (CAR) T-cell therapy, Krish Patel, MD, a lymphoma specialist with Swedish Cancer Institute in Seattle, said in an adjoining presentation. Fortunately, he said, some treatments are showing early promise.
Here’s a closer look at the presentations by Dr. Wagner-Johnston and Dr. Patel.
Frontline MCL: Age Helps Determine Best Approach
“For older and less fit patients, the standard approach has typically been bendamustine (Bendeka, Treanda) and rituximab (Rituxan), and the median progression-free survival is about 4 years, with overall survival not reached at a median 5 years of follow-up,” Dr. Wagner-Johnston said.
Low doses of the chemotherapy drug cytarabine have been added to the bendamustine-rituximab regimen, with encouraging results, she said. “Certainly there’s more toxicity associated even with lower doses, but those data look fairly promising.”
For younger and fit patients, “the standard of care approach has been to administer intensive chemoimmunotherapy that contains high-dose cytarabine, and then that’s typically followed with an autologous stem cell transplant,” she said. A 2016 study reported median progression-free survival of 8.5 years and median overall survival of 12.7 years.
Now, second-generation Bruton tyrosine kinase inhibitors “look very promising” in the frontline setting, Dr. Wagner-Johnston said.
The road has been rocky, however. The SHINE trial of more than 500 patients aged over 65 found that adding ibrutinib to bendamustine-rituximab improved progression-free survival. “However, progression-free survival did not [connect] to an overall survival benefit, and that’s likely due to the toxicity seen with ibrutinib,” she said.
“It’s not surprising to many of you that ibrutinib has been removed from the FDA label for mantle cell lymphoma,” she said. However, “second-generation [Bruton tyrosine kinase inhibitors] are known to be associated with less toxicity and potentially increased potency.”
What about Bruton tyrosine kinase inhibitors in younger and fitter patients? The TRIANGLE trial demonstrated their benefit, Dr. Wagner-Johnston said, linking ibrutinib to improvement in progression-free survival.
However, “it’s really too early to evaluate the statistical significance for overall survival.” And while the study looks at therapy without stem cell transplant, she believes it’s too early to know whether that’s a good option.
Dr. Wagner-Johnston tackled another topic: Can Bruton tyrosine kinase inhibitors overcome the poor prognosis seen with MCL with TP53 mutation? For now, the limitations of research makes it “hard to know,” she said, although early results of the BOVen trial are promising.
Relapsed/Refractory MCL: Better Options Are Still Needed
In his presentation, Dr. Patel spoke about therapy in patients with MCL and relapsed/refractory disease. “We know that outcomes for patients who progress on covalent [Bruton tyrosine kinase inhibitors] is really dismal,” he said. “This has been shown by multiple groups now across the globe.”
Noncovalent Bruton tyrosine kinase inhibitors are now an option, he noted. “We do understand that they work for some patients, and it can be quite useful, but even noncovalent [Bruton tyrosine kinase inhibitors] themselves are susceptible to resistance mutations. We’ve seen that in the [chronic lymphocytic leukemia] world.”
Dr. Patel asked the audience, “Why not just give everybody CAR T-cells, post-[Bruton tyrosine kinase inhibitors]? You get a CAR T-cell! You get a CAR T-cell! Everybody gets one.”
However, he noted, “Unfortunately, mantle cell lymphoma patients experience the worst high-grade toxicity when receiving CD19[-targeted] CAR T-cells.”
Are there better options? At the moment, “really, really early data” suggest benefits from molecular glues and degraders, novel inhibitors, antibody-drug conjugates, novel CAR T-cells, and bispecific antibodies, Dr. Patel said.
“All of these tools are in clinical trials, and hopefully some of them will help,” he said.
Disclosures were not provided. Dr. Wagner-Johnston recently disclosed advisory committee/board of directors’ relationships with ADC Therapeutics, Regeneron, Calibr, and Verastem. Dr. Patel recently disclosed ties with a long list of pharmaceutical companies, including AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Genentech, Janssen, Merck, and others.
A version of this article first appeared on Medscape.com.
In the frontline setting, findings suggest that regimens should differ significantly on the basis of whether patients are older or younger, whereas more data are needed to understand whether treatment can overcome poor prognoses in patients with TP53 mutations, lymphoma specialist Nina Wagner-Johnston, MD, of Johns Hopkins University School of Medicine, Baltimore, said in a presentation at the annual meeting of the Society of Hematologic Oncology (SOHO) 2024 in Houston, Texas.
On the relapsed/refractory front, patients need better options after treatment with Bruton tyrosine kinase inhibitors or chimeric antigen receptor (CAR) T-cell therapy, Krish Patel, MD, a lymphoma specialist with Swedish Cancer Institute in Seattle, said in an adjoining presentation. Fortunately, he said, some treatments are showing early promise.
Here’s a closer look at the presentations by Dr. Wagner-Johnston and Dr. Patel.
Frontline MCL: Age Helps Determine Best Approach
“For older and less fit patients, the standard approach has typically been bendamustine (Bendeka, Treanda) and rituximab (Rituxan), and the median progression-free survival is about 4 years, with overall survival not reached at a median 5 years of follow-up,” Dr. Wagner-Johnston said.
Low doses of the chemotherapy drug cytarabine have been added to the bendamustine-rituximab regimen, with encouraging results, she said. “Certainly there’s more toxicity associated even with lower doses, but those data look fairly promising.”
For younger and fit patients, “the standard of care approach has been to administer intensive chemoimmunotherapy that contains high-dose cytarabine, and then that’s typically followed with an autologous stem cell transplant,” she said. A 2016 study reported median progression-free survival of 8.5 years and median overall survival of 12.7 years.
Now, second-generation Bruton tyrosine kinase inhibitors “look very promising” in the frontline setting, Dr. Wagner-Johnston said.
The road has been rocky, however. The SHINE trial of more than 500 patients aged over 65 found that adding ibrutinib to bendamustine-rituximab improved progression-free survival. “However, progression-free survival did not [connect] to an overall survival benefit, and that’s likely due to the toxicity seen with ibrutinib,” she said.
“It’s not surprising to many of you that ibrutinib has been removed from the FDA label for mantle cell lymphoma,” she said. However, “second-generation [Bruton tyrosine kinase inhibitors] are known to be associated with less toxicity and potentially increased potency.”
What about Bruton tyrosine kinase inhibitors in younger and fitter patients? The TRIANGLE trial demonstrated their benefit, Dr. Wagner-Johnston said, linking ibrutinib to improvement in progression-free survival.
However, “it’s really too early to evaluate the statistical significance for overall survival.” And while the study looks at therapy without stem cell transplant, she believes it’s too early to know whether that’s a good option.
Dr. Wagner-Johnston tackled another topic: Can Bruton tyrosine kinase inhibitors overcome the poor prognosis seen with MCL with TP53 mutation? For now, the limitations of research makes it “hard to know,” she said, although early results of the BOVen trial are promising.
Relapsed/Refractory MCL: Better Options Are Still Needed
In his presentation, Dr. Patel spoke about therapy in patients with MCL and relapsed/refractory disease. “We know that outcomes for patients who progress on covalent [Bruton tyrosine kinase inhibitors] is really dismal,” he said. “This has been shown by multiple groups now across the globe.”
Noncovalent Bruton tyrosine kinase inhibitors are now an option, he noted. “We do understand that they work for some patients, and it can be quite useful, but even noncovalent [Bruton tyrosine kinase inhibitors] themselves are susceptible to resistance mutations. We’ve seen that in the [chronic lymphocytic leukemia] world.”
Dr. Patel asked the audience, “Why not just give everybody CAR T-cells, post-[Bruton tyrosine kinase inhibitors]? You get a CAR T-cell! You get a CAR T-cell! Everybody gets one.”
However, he noted, “Unfortunately, mantle cell lymphoma patients experience the worst high-grade toxicity when receiving CD19[-targeted] CAR T-cells.”
Are there better options? At the moment, “really, really early data” suggest benefits from molecular glues and degraders, novel inhibitors, antibody-drug conjugates, novel CAR T-cells, and bispecific antibodies, Dr. Patel said.
“All of these tools are in clinical trials, and hopefully some of them will help,” he said.
Disclosures were not provided. Dr. Wagner-Johnston recently disclosed advisory committee/board of directors’ relationships with ADC Therapeutics, Regeneron, Calibr, and Verastem. Dr. Patel recently disclosed ties with a long list of pharmaceutical companies, including AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Genentech, Janssen, Merck, and others.
A version of this article first appeared on Medscape.com.
In the frontline setting, findings suggest that regimens should differ significantly on the basis of whether patients are older or younger, whereas more data are needed to understand whether treatment can overcome poor prognoses in patients with TP53 mutations, lymphoma specialist Nina Wagner-Johnston, MD, of Johns Hopkins University School of Medicine, Baltimore, said in a presentation at the annual meeting of the Society of Hematologic Oncology (SOHO) 2024 in Houston, Texas.
On the relapsed/refractory front, patients need better options after treatment with Bruton tyrosine kinase inhibitors or chimeric antigen receptor (CAR) T-cell therapy, Krish Patel, MD, a lymphoma specialist with Swedish Cancer Institute in Seattle, said in an adjoining presentation. Fortunately, he said, some treatments are showing early promise.
Here’s a closer look at the presentations by Dr. Wagner-Johnston and Dr. Patel.
Frontline MCL: Age Helps Determine Best Approach
“For older and less fit patients, the standard approach has typically been bendamustine (Bendeka, Treanda) and rituximab (Rituxan), and the median progression-free survival is about 4 years, with overall survival not reached at a median 5 years of follow-up,” Dr. Wagner-Johnston said.
Low doses of the chemotherapy drug cytarabine have been added to the bendamustine-rituximab regimen, with encouraging results, she said. “Certainly there’s more toxicity associated even with lower doses, but those data look fairly promising.”
For younger and fit patients, “the standard of care approach has been to administer intensive chemoimmunotherapy that contains high-dose cytarabine, and then that’s typically followed with an autologous stem cell transplant,” she said. A 2016 study reported median progression-free survival of 8.5 years and median overall survival of 12.7 years.
Now, second-generation Bruton tyrosine kinase inhibitors “look very promising” in the frontline setting, Dr. Wagner-Johnston said.
The road has been rocky, however. The SHINE trial of more than 500 patients aged over 65 found that adding ibrutinib to bendamustine-rituximab improved progression-free survival. “However, progression-free survival did not [connect] to an overall survival benefit, and that’s likely due to the toxicity seen with ibrutinib,” she said.
“It’s not surprising to many of you that ibrutinib has been removed from the FDA label for mantle cell lymphoma,” she said. However, “second-generation [Bruton tyrosine kinase inhibitors] are known to be associated with less toxicity and potentially increased potency.”
What about Bruton tyrosine kinase inhibitors in younger and fitter patients? The TRIANGLE trial demonstrated their benefit, Dr. Wagner-Johnston said, linking ibrutinib to improvement in progression-free survival.
However, “it’s really too early to evaluate the statistical significance for overall survival.” And while the study looks at therapy without stem cell transplant, she believes it’s too early to know whether that’s a good option.
Dr. Wagner-Johnston tackled another topic: Can Bruton tyrosine kinase inhibitors overcome the poor prognosis seen with MCL with TP53 mutation? For now, the limitations of research makes it “hard to know,” she said, although early results of the BOVen trial are promising.
Relapsed/Refractory MCL: Better Options Are Still Needed
In his presentation, Dr. Patel spoke about therapy in patients with MCL and relapsed/refractory disease. “We know that outcomes for patients who progress on covalent [Bruton tyrosine kinase inhibitors] is really dismal,” he said. “This has been shown by multiple groups now across the globe.”
Noncovalent Bruton tyrosine kinase inhibitors are now an option, he noted. “We do understand that they work for some patients, and it can be quite useful, but even noncovalent [Bruton tyrosine kinase inhibitors] themselves are susceptible to resistance mutations. We’ve seen that in the [chronic lymphocytic leukemia] world.”
Dr. Patel asked the audience, “Why not just give everybody CAR T-cells, post-[Bruton tyrosine kinase inhibitors]? You get a CAR T-cell! You get a CAR T-cell! Everybody gets one.”
However, he noted, “Unfortunately, mantle cell lymphoma patients experience the worst high-grade toxicity when receiving CD19[-targeted] CAR T-cells.”
Are there better options? At the moment, “really, really early data” suggest benefits from molecular glues and degraders, novel inhibitors, antibody-drug conjugates, novel CAR T-cells, and bispecific antibodies, Dr. Patel said.
“All of these tools are in clinical trials, and hopefully some of them will help,” he said.
Disclosures were not provided. Dr. Wagner-Johnston recently disclosed advisory committee/board of directors’ relationships with ADC Therapeutics, Regeneron, Calibr, and Verastem. Dr. Patel recently disclosed ties with a long list of pharmaceutical companies, including AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Genentech, Janssen, Merck, and others.
A version of this article first appeared on Medscape.com.
FROM SOHO 2024
Debate: Should CAR T Best Be Used in Early MM Relapse?
Will CAR T be best used in early relapse? Experts debated this question at the annual meeting of the Society of Hematologic Oncology. Based on attendees’ votes, at least one side of the debate emerged victorious.
Krina Patel, MD, an associate professor at the University of Texas MD Anderson Cancer Center, Houston, came out swinging with earnest support for using CAR T in early relapse. Saad Z. Usmani, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York City, and Cornell University, Ithaca, New York, argued in favor of being “a little more circumspect.”
Dr. Patel: Yes, Earlier Is Better
A pre-debate audience poll leaned Dr. Patel’s way, with about 59% of 73 votes favoring CAR T in early relapse, 33% favoring reserving CAR T for patients who relapse after three or more lines of therapy, and 8% undecided.
“CAR T is not just a drug — it’s an actual therapy that takes a lot of logistics, as well as bridging therapy and all these other things to take into account,” said Dr. Patel. “And again, when I can go earlier, I have control over some of this.”
Furthermore, randomized phase 3 data from the KarMMA-3 study and the CARTITUDE-4 study showed that multiple standard therapies were not as good as CAR T in the early relapse setting, she said, pointing to the respective hazard ratios for disease progression or death with CAR T vs standard therapies of 0.49 and 0.26.
CARTITUDE-4 also suggested that manufacturing failures are more likely in later relapse — when time is already of greater essence, she said, noting that it can take an additional 3 months when restarting the process.
When it comes to toxicity, yes, it is a concern, she said.
“But we know how to decrease toxicity,” she stressed. “And again, with our second- and third-line approaches, we actually have better therapies to give for bridging.”
Quality of life is another important consideration, Dr. Patel said, noting only CAR T offers a “one-and-done” therapy that helps patients “truly feel better.”
“They’re not having to come into hospitals as often, and this is not just for months; it’s for years,” she said. “To be able to give that to somebody is huge, and again, we have objective data that show that compared to our standard of care therapies, patients do better in almost every realm of quality of life metrics.”
Dr. Patel also pointed to recent data from a retrospective study showing that for bridging therapy, less is more when disease is controlled, and in the early-line setting, more and safer options are available for reducing tumor burden.
Early CAR T is better for older or frail patients as well, she argued, noting that these patients don’t have time to wait, and a new study demonstrates that they tend to do well with CAR T in the early relapse setting.
The choice for early CAR T is clear in patients with high-risk disease, but Dr. Patel stressed that it shouldn’t be reserved for those patients, asking, “When has anything worked well for patients with high-risk disease and not [also] better for standard-risk patients?”
“And why give only 20%-25% of your patients [who actually reach fifth-line treatment] access to something that we know has really revolutionized myeloma therapy?” she said.
Many patients don’t have access, and that’s an issue, she acknowledged, adding: “But for those who do, we really should be giving it to them as soon as possible.”
Dr. Usmani: Reserve CAR T for Later Relapse
Not so fast, said Dr. Usmani. “All of these therapies are doing wonders for our patients, and we believe in them, but we have to be a little circumspect in looking at this data more closely and not just with emotions,” he added, noting that many options exist for patients in a first or second relapse, and new options are emerging.
There is also a “harsh reality” in terms of CAR T availability, he noted, explaining that, in 2021, about 180,000 people were living with MM, and about two thirds of those had relapsed disease. Meanwhile, fewer than 1000 CAR T products have been delivered each year for patients with relapsed MM since they were approved in this setting in the United States.
“So, it’s a pipe dream, seriously, that we will be able to utilize CAR T for all patients in early relapsed disease,” he said, adding that capacity will remain an issue because of limited resources.
The existing data, including from KarMMa-3 and CARTITUDE-4, show little potential for long-term benefit with early vs later CAR T.
“There is no plateau,” he said of the survival curves in KarMMa-3, underscoring the lack of a difference in overall survival benefit based on CAR T timing.
The CARTITUDE-4 curves “look great,” and it may be that a “small plateau emerges,” but they don’t demonstrate a benefit of earlier vs later CAR T, he said.
As Dr. Patel noted, there are few treatment options for patients with anti-CD38 monoclonal antibody and immunomodulatory drug resistance at first relapse. However, that situation will soon change, Dr. Usmani stated.
“Guess what? Belamaf is coming to the rescue!” he said of the off-the-shelf and more accessible B-cell maturation antigen-targeted antibody-drug conjugate belantamab mafodotin, which has recently been evaluated in the DREAMM 7 and DREAMM 8 trials.
DREAMM 7 demonstrated improved survival vs daratumumab, bortezomib, and dexamethasone in the relapsed/refractory MM setting when used in combination with bortezomib and dexamethasone. DREAMM 8 shows similar benefit with belantamab mafodotin, pomalidomide, and dexamethasone vs pomalidomide, bortezomib, and dexamethasone in lenalidomide-exposed patients with relapsed or refractory MM.
“Belamaf combinations in the one to three lines [of prior therapy] setting look really good,” he said, noting a particular benefit for progression-free survival and a trend toward improved overall survival.
Considering these factors, as well as the risk for cytopenias and the subsequent risk for infection in most patients who undergo CAR T-cell therapy and the known potential risk for secondary malignancies, Dr. Usmani said that he will remain “in the camp of being really careful in selecting CAR T patients for early relapse” until more is known about the risks.
“CAR T for all is not the answer. I think we have to be careful in picking CAR T patients; it’s not a zero-sum game here,” he said, stressing that “there are too many unknowns with the use of early CAR T therapy.”
“It makes sense in some, but not for everyone,” he said, emphasizing the importance of including patients in the discussion.
“The great thing is we have all these options for our patients,” he said.
Dr. Usmani persuaded at least a few colleagues: The final vote showed 42% of 124 voters supported early CAR T, compared with 52% who supported CAR T after three or more lines of therapy and 6% who remained undecided.
A version of this article first appeared on Medscape.com.
Will CAR T be best used in early relapse? Experts debated this question at the annual meeting of the Society of Hematologic Oncology. Based on attendees’ votes, at least one side of the debate emerged victorious.
Krina Patel, MD, an associate professor at the University of Texas MD Anderson Cancer Center, Houston, came out swinging with earnest support for using CAR T in early relapse. Saad Z. Usmani, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York City, and Cornell University, Ithaca, New York, argued in favor of being “a little more circumspect.”
Dr. Patel: Yes, Earlier Is Better
A pre-debate audience poll leaned Dr. Patel’s way, with about 59% of 73 votes favoring CAR T in early relapse, 33% favoring reserving CAR T for patients who relapse after three or more lines of therapy, and 8% undecided.
“CAR T is not just a drug — it’s an actual therapy that takes a lot of logistics, as well as bridging therapy and all these other things to take into account,” said Dr. Patel. “And again, when I can go earlier, I have control over some of this.”
Furthermore, randomized phase 3 data from the KarMMA-3 study and the CARTITUDE-4 study showed that multiple standard therapies were not as good as CAR T in the early relapse setting, she said, pointing to the respective hazard ratios for disease progression or death with CAR T vs standard therapies of 0.49 and 0.26.
CARTITUDE-4 also suggested that manufacturing failures are more likely in later relapse — when time is already of greater essence, she said, noting that it can take an additional 3 months when restarting the process.
When it comes to toxicity, yes, it is a concern, she said.
“But we know how to decrease toxicity,” she stressed. “And again, with our second- and third-line approaches, we actually have better therapies to give for bridging.”
Quality of life is another important consideration, Dr. Patel said, noting only CAR T offers a “one-and-done” therapy that helps patients “truly feel better.”
“They’re not having to come into hospitals as often, and this is not just for months; it’s for years,” she said. “To be able to give that to somebody is huge, and again, we have objective data that show that compared to our standard of care therapies, patients do better in almost every realm of quality of life metrics.”
Dr. Patel also pointed to recent data from a retrospective study showing that for bridging therapy, less is more when disease is controlled, and in the early-line setting, more and safer options are available for reducing tumor burden.
Early CAR T is better for older or frail patients as well, she argued, noting that these patients don’t have time to wait, and a new study demonstrates that they tend to do well with CAR T in the early relapse setting.
The choice for early CAR T is clear in patients with high-risk disease, but Dr. Patel stressed that it shouldn’t be reserved for those patients, asking, “When has anything worked well for patients with high-risk disease and not [also] better for standard-risk patients?”
“And why give only 20%-25% of your patients [who actually reach fifth-line treatment] access to something that we know has really revolutionized myeloma therapy?” she said.
Many patients don’t have access, and that’s an issue, she acknowledged, adding: “But for those who do, we really should be giving it to them as soon as possible.”
Dr. Usmani: Reserve CAR T for Later Relapse
Not so fast, said Dr. Usmani. “All of these therapies are doing wonders for our patients, and we believe in them, but we have to be a little circumspect in looking at this data more closely and not just with emotions,” he added, noting that many options exist for patients in a first or second relapse, and new options are emerging.
There is also a “harsh reality” in terms of CAR T availability, he noted, explaining that, in 2021, about 180,000 people were living with MM, and about two thirds of those had relapsed disease. Meanwhile, fewer than 1000 CAR T products have been delivered each year for patients with relapsed MM since they were approved in this setting in the United States.
“So, it’s a pipe dream, seriously, that we will be able to utilize CAR T for all patients in early relapsed disease,” he said, adding that capacity will remain an issue because of limited resources.
The existing data, including from KarMMa-3 and CARTITUDE-4, show little potential for long-term benefit with early vs later CAR T.
“There is no plateau,” he said of the survival curves in KarMMa-3, underscoring the lack of a difference in overall survival benefit based on CAR T timing.
The CARTITUDE-4 curves “look great,” and it may be that a “small plateau emerges,” but they don’t demonstrate a benefit of earlier vs later CAR T, he said.
As Dr. Patel noted, there are few treatment options for patients with anti-CD38 monoclonal antibody and immunomodulatory drug resistance at first relapse. However, that situation will soon change, Dr. Usmani stated.
“Guess what? Belamaf is coming to the rescue!” he said of the off-the-shelf and more accessible B-cell maturation antigen-targeted antibody-drug conjugate belantamab mafodotin, which has recently been evaluated in the DREAMM 7 and DREAMM 8 trials.
DREAMM 7 demonstrated improved survival vs daratumumab, bortezomib, and dexamethasone in the relapsed/refractory MM setting when used in combination with bortezomib and dexamethasone. DREAMM 8 shows similar benefit with belantamab mafodotin, pomalidomide, and dexamethasone vs pomalidomide, bortezomib, and dexamethasone in lenalidomide-exposed patients with relapsed or refractory MM.
“Belamaf combinations in the one to three lines [of prior therapy] setting look really good,” he said, noting a particular benefit for progression-free survival and a trend toward improved overall survival.
Considering these factors, as well as the risk for cytopenias and the subsequent risk for infection in most patients who undergo CAR T-cell therapy and the known potential risk for secondary malignancies, Dr. Usmani said that he will remain “in the camp of being really careful in selecting CAR T patients for early relapse” until more is known about the risks.
“CAR T for all is not the answer. I think we have to be careful in picking CAR T patients; it’s not a zero-sum game here,” he said, stressing that “there are too many unknowns with the use of early CAR T therapy.”
“It makes sense in some, but not for everyone,” he said, emphasizing the importance of including patients in the discussion.
“The great thing is we have all these options for our patients,” he said.
Dr. Usmani persuaded at least a few colleagues: The final vote showed 42% of 124 voters supported early CAR T, compared with 52% who supported CAR T after three or more lines of therapy and 6% who remained undecided.
A version of this article first appeared on Medscape.com.
Will CAR T be best used in early relapse? Experts debated this question at the annual meeting of the Society of Hematologic Oncology. Based on attendees’ votes, at least one side of the debate emerged victorious.
Krina Patel, MD, an associate professor at the University of Texas MD Anderson Cancer Center, Houston, came out swinging with earnest support for using CAR T in early relapse. Saad Z. Usmani, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York City, and Cornell University, Ithaca, New York, argued in favor of being “a little more circumspect.”
Dr. Patel: Yes, Earlier Is Better
A pre-debate audience poll leaned Dr. Patel’s way, with about 59% of 73 votes favoring CAR T in early relapse, 33% favoring reserving CAR T for patients who relapse after three or more lines of therapy, and 8% undecided.
“CAR T is not just a drug — it’s an actual therapy that takes a lot of logistics, as well as bridging therapy and all these other things to take into account,” said Dr. Patel. “And again, when I can go earlier, I have control over some of this.”
Furthermore, randomized phase 3 data from the KarMMA-3 study and the CARTITUDE-4 study showed that multiple standard therapies were not as good as CAR T in the early relapse setting, she said, pointing to the respective hazard ratios for disease progression or death with CAR T vs standard therapies of 0.49 and 0.26.
CARTITUDE-4 also suggested that manufacturing failures are more likely in later relapse — when time is already of greater essence, she said, noting that it can take an additional 3 months when restarting the process.
When it comes to toxicity, yes, it is a concern, she said.
“But we know how to decrease toxicity,” she stressed. “And again, with our second- and third-line approaches, we actually have better therapies to give for bridging.”
Quality of life is another important consideration, Dr. Patel said, noting only CAR T offers a “one-and-done” therapy that helps patients “truly feel better.”
“They’re not having to come into hospitals as often, and this is not just for months; it’s for years,” she said. “To be able to give that to somebody is huge, and again, we have objective data that show that compared to our standard of care therapies, patients do better in almost every realm of quality of life metrics.”
Dr. Patel also pointed to recent data from a retrospective study showing that for bridging therapy, less is more when disease is controlled, and in the early-line setting, more and safer options are available for reducing tumor burden.
Early CAR T is better for older or frail patients as well, she argued, noting that these patients don’t have time to wait, and a new study demonstrates that they tend to do well with CAR T in the early relapse setting.
The choice for early CAR T is clear in patients with high-risk disease, but Dr. Patel stressed that it shouldn’t be reserved for those patients, asking, “When has anything worked well for patients with high-risk disease and not [also] better for standard-risk patients?”
“And why give only 20%-25% of your patients [who actually reach fifth-line treatment] access to something that we know has really revolutionized myeloma therapy?” she said.
Many patients don’t have access, and that’s an issue, she acknowledged, adding: “But for those who do, we really should be giving it to them as soon as possible.”
Dr. Usmani: Reserve CAR T for Later Relapse
Not so fast, said Dr. Usmani. “All of these therapies are doing wonders for our patients, and we believe in them, but we have to be a little circumspect in looking at this data more closely and not just with emotions,” he added, noting that many options exist for patients in a first or second relapse, and new options are emerging.
There is also a “harsh reality” in terms of CAR T availability, he noted, explaining that, in 2021, about 180,000 people were living with MM, and about two thirds of those had relapsed disease. Meanwhile, fewer than 1000 CAR T products have been delivered each year for patients with relapsed MM since they were approved in this setting in the United States.
“So, it’s a pipe dream, seriously, that we will be able to utilize CAR T for all patients in early relapsed disease,” he said, adding that capacity will remain an issue because of limited resources.
The existing data, including from KarMMa-3 and CARTITUDE-4, show little potential for long-term benefit with early vs later CAR T.
“There is no plateau,” he said of the survival curves in KarMMa-3, underscoring the lack of a difference in overall survival benefit based on CAR T timing.
The CARTITUDE-4 curves “look great,” and it may be that a “small plateau emerges,” but they don’t demonstrate a benefit of earlier vs later CAR T, he said.
As Dr. Patel noted, there are few treatment options for patients with anti-CD38 monoclonal antibody and immunomodulatory drug resistance at first relapse. However, that situation will soon change, Dr. Usmani stated.
“Guess what? Belamaf is coming to the rescue!” he said of the off-the-shelf and more accessible B-cell maturation antigen-targeted antibody-drug conjugate belantamab mafodotin, which has recently been evaluated in the DREAMM 7 and DREAMM 8 trials.
DREAMM 7 demonstrated improved survival vs daratumumab, bortezomib, and dexamethasone in the relapsed/refractory MM setting when used in combination with bortezomib and dexamethasone. DREAMM 8 shows similar benefit with belantamab mafodotin, pomalidomide, and dexamethasone vs pomalidomide, bortezomib, and dexamethasone in lenalidomide-exposed patients with relapsed or refractory MM.
“Belamaf combinations in the one to three lines [of prior therapy] setting look really good,” he said, noting a particular benefit for progression-free survival and a trend toward improved overall survival.
Considering these factors, as well as the risk for cytopenias and the subsequent risk for infection in most patients who undergo CAR T-cell therapy and the known potential risk for secondary malignancies, Dr. Usmani said that he will remain “in the camp of being really careful in selecting CAR T patients for early relapse” until more is known about the risks.
“CAR T for all is not the answer. I think we have to be careful in picking CAR T patients; it’s not a zero-sum game here,” he said, stressing that “there are too many unknowns with the use of early CAR T therapy.”
“It makes sense in some, but not for everyone,” he said, emphasizing the importance of including patients in the discussion.
“The great thing is we have all these options for our patients,” he said.
Dr. Usmani persuaded at least a few colleagues: The final vote showed 42% of 124 voters supported early CAR T, compared with 52% who supported CAR T after three or more lines of therapy and 6% who remained undecided.
A version of this article first appeared on Medscape.com.
FROM SOHO 2024
Whole Health Oncology—Just Do It: Making Whole Person Cancer Care Routine and Regular at the Dayton VA Medical Center (DVAMC)
Background
VA Whole Health (WH) is an approach that empowers and equips people to take charge of their health and well-being. In 2020, 18 WH Flagship sites demonstrated reduced opiate use and smaller increases in pharmacy costs as well as favorable veteran self-reported measures. VA mandated WH integration into mental health and primary care. Purose: To incorporate WH within Dayton VA cancer care, using the Personal Health Inventory (PHI) as an intake tool, a tumor-agnostic WH oncology clinic was established.
Methods
Led by an oncologist, a referral-based clinic opened in 2021. Pre-work included EHR items (stop codes/templates), staff training and leverage of mental health integration. VA’s generic PHI was utilized until an oncology-specific PHI was developed by leaders in the field.(3-5) Clinic data was tracked.
Results
170 visits offered (June 2021-May 2024). 32 referrals received (one without cancer; deaths: two pre-intake/five post-intake); 70 appointments occurred among 30 veterans (30 intake/40 follow-up) for 41% fill rate (up 5% from 1st six months). 96% PHI completion rate. Referral sources: fellows (43%), attendings (17%), PCP (3%), Survivorship Clinic (3%), self-referral (33%)--40% of these from cancer support group members. Cancer types (one dual-diagnosis; total >100%): 24% breast, 17% prostate, 17% NSCLC, 10% NHL, 10% pancreatic, 7% Head/Neck, 7% SCLC, 3% each colon/esophageal/kidney. Cancer Stages represented: I (10%), II (20%), III (23%) and IV (47%). Participant info: Age range (36-85); 69% male and 31% female with 86% on active cancer therapy (hormonal, immune-, chemo- or chemoradiation). Supplements were discussed at 26% of visits and referrals ordered at 27% (4-massage therapy, 1-acupuncture, 1-chiropractic, 2-health coaching, 1-cardiology, 1-lymphedema therapy, 1-social work, 1-survivorship clinic, 1-yoga, 1-diabetes education, 1-ENT, 1-nutrition, 1-pathology, 1-pulmonary, 1-prosthetics).
Conclusions
WH within cancer care is feasible for veterans on active treatment (all types/stages) and at a non-Flagship/unfunded site. Veterans gain introduction to WH through the PHI and Complementary-Integrative Health referrals (VA Directive 1137). Cancer support group attendance prompts WH clinic self-referrals. Next steps at DVAMC are to offer mind-body approaches such as virtual reality experiences in the infusion room and VA CALM sessions via asynchronous online delivery; funding would support WH evolution in oncology.
Background
VA Whole Health (WH) is an approach that empowers and equips people to take charge of their health and well-being. In 2020, 18 WH Flagship sites demonstrated reduced opiate use and smaller increases in pharmacy costs as well as favorable veteran self-reported measures. VA mandated WH integration into mental health and primary care. Purose: To incorporate WH within Dayton VA cancer care, using the Personal Health Inventory (PHI) as an intake tool, a tumor-agnostic WH oncology clinic was established.
Methods
Led by an oncologist, a referral-based clinic opened in 2021. Pre-work included EHR items (stop codes/templates), staff training and leverage of mental health integration. VA’s generic PHI was utilized until an oncology-specific PHI was developed by leaders in the field.(3-5) Clinic data was tracked.
Results
170 visits offered (June 2021-May 2024). 32 referrals received (one without cancer; deaths: two pre-intake/five post-intake); 70 appointments occurred among 30 veterans (30 intake/40 follow-up) for 41% fill rate (up 5% from 1st six months). 96% PHI completion rate. Referral sources: fellows (43%), attendings (17%), PCP (3%), Survivorship Clinic (3%), self-referral (33%)--40% of these from cancer support group members. Cancer types (one dual-diagnosis; total >100%): 24% breast, 17% prostate, 17% NSCLC, 10% NHL, 10% pancreatic, 7% Head/Neck, 7% SCLC, 3% each colon/esophageal/kidney. Cancer Stages represented: I (10%), II (20%), III (23%) and IV (47%). Participant info: Age range (36-85); 69% male and 31% female with 86% on active cancer therapy (hormonal, immune-, chemo- or chemoradiation). Supplements were discussed at 26% of visits and referrals ordered at 27% (4-massage therapy, 1-acupuncture, 1-chiropractic, 2-health coaching, 1-cardiology, 1-lymphedema therapy, 1-social work, 1-survivorship clinic, 1-yoga, 1-diabetes education, 1-ENT, 1-nutrition, 1-pathology, 1-pulmonary, 1-prosthetics).
Conclusions
WH within cancer care is feasible for veterans on active treatment (all types/stages) and at a non-Flagship/unfunded site. Veterans gain introduction to WH through the PHI and Complementary-Integrative Health referrals (VA Directive 1137). Cancer support group attendance prompts WH clinic self-referrals. Next steps at DVAMC are to offer mind-body approaches such as virtual reality experiences in the infusion room and VA CALM sessions via asynchronous online delivery; funding would support WH evolution in oncology.
Background
VA Whole Health (WH) is an approach that empowers and equips people to take charge of their health and well-being. In 2020, 18 WH Flagship sites demonstrated reduced opiate use and smaller increases in pharmacy costs as well as favorable veteran self-reported measures. VA mandated WH integration into mental health and primary care. Purose: To incorporate WH within Dayton VA cancer care, using the Personal Health Inventory (PHI) as an intake tool, a tumor-agnostic WH oncology clinic was established.
Methods
Led by an oncologist, a referral-based clinic opened in 2021. Pre-work included EHR items (stop codes/templates), staff training and leverage of mental health integration. VA’s generic PHI was utilized until an oncology-specific PHI was developed by leaders in the field.(3-5) Clinic data was tracked.
Results
170 visits offered (June 2021-May 2024). 32 referrals received (one without cancer; deaths: two pre-intake/five post-intake); 70 appointments occurred among 30 veterans (30 intake/40 follow-up) for 41% fill rate (up 5% from 1st six months). 96% PHI completion rate. Referral sources: fellows (43%), attendings (17%), PCP (3%), Survivorship Clinic (3%), self-referral (33%)--40% of these from cancer support group members. Cancer types (one dual-diagnosis; total >100%): 24% breast, 17% prostate, 17% NSCLC, 10% NHL, 10% pancreatic, 7% Head/Neck, 7% SCLC, 3% each colon/esophageal/kidney. Cancer Stages represented: I (10%), II (20%), III (23%) and IV (47%). Participant info: Age range (36-85); 69% male and 31% female with 86% on active cancer therapy (hormonal, immune-, chemo- or chemoradiation). Supplements were discussed at 26% of visits and referrals ordered at 27% (4-massage therapy, 1-acupuncture, 1-chiropractic, 2-health coaching, 1-cardiology, 1-lymphedema therapy, 1-social work, 1-survivorship clinic, 1-yoga, 1-diabetes education, 1-ENT, 1-nutrition, 1-pathology, 1-pulmonary, 1-prosthetics).
Conclusions
WH within cancer care is feasible for veterans on active treatment (all types/stages) and at a non-Flagship/unfunded site. Veterans gain introduction to WH through the PHI and Complementary-Integrative Health referrals (VA Directive 1137). Cancer support group attendance prompts WH clinic self-referrals. Next steps at DVAMC are to offer mind-body approaches such as virtual reality experiences in the infusion room and VA CALM sessions via asynchronous online delivery; funding would support WH evolution in oncology.
A Simple Blood Test May Predict Cancer Risk in T2D
TOPLINE:
potentially enabling the identification of higher-risk individuals through a simple blood test.
METHODOLOGY:
- T2D is associated with an increased risk for obesity-related cancers, including breast, renal, uterine, thyroid, ovarian, and gastrointestinal cancers, as well as multiple myeloma, possibly because of chronic low-grade inflammation.
- Researchers explored whether the markers of inflammation IL-6, tumor necrosis factor alpha (TNF-alpha), and high-sensitivity C-reactive protein (hsCRP) can serve as predictive biomarkers for obesity-related cancers in patients recently diagnosed with T2D.
- They identified patients with recent-onset T2D and no prior history of cancer participating in the ongoing Danish Centre for Strategic Research in Type 2 Diabetes cohort study.
- At study initiation, plasma levels of IL-6 and TNF-alpha were measured using Meso Scale Discovery assays, and serum levels of hsCRP were measured using immunofluorometric assays.
TAKEAWAY:
- Among 6,466 eligible patients (40.5% women; median age, 60.9 years), 327 developed obesity-related cancers over a median follow-up of 8.8 years.
- Each SD increase in log-transformed IL-6 levels increased the risk for obesity-related cancers by 19%.
- The researchers did not find a strong association between TNF-alpha or hsCRP and obesity-related cancers.
- The addition of baseline IL-6 levels to other well-known risk factors for obesity-related cancers improved the performance of a cancer prediction model from 0.685 to 0.693, translating to a small but important increase in the ability to predict whether an individual would develop one of these cancers.
IN PRACTICE:
“In future, a simple blood test could identify those at higher risk of the cancers,” said the study’s lead author in an accompanying press release.
SOURCE:
The study was led by Mathilde D. Bennetsen, Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark, and published online on August 27 as an early release from the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.
LIMITATIONS:
No limitations were discussed in this abstract. However, the reliance on registry data may have introduced potential biases related to data accuracy and completeness.
DISCLOSURES:
The Danish Centre for Strategic Research in Type 2 Diabetes was supported by grants from the Danish Agency for Science and the Novo Nordisk Foundation. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
potentially enabling the identification of higher-risk individuals through a simple blood test.
METHODOLOGY:
- T2D is associated with an increased risk for obesity-related cancers, including breast, renal, uterine, thyroid, ovarian, and gastrointestinal cancers, as well as multiple myeloma, possibly because of chronic low-grade inflammation.
- Researchers explored whether the markers of inflammation IL-6, tumor necrosis factor alpha (TNF-alpha), and high-sensitivity C-reactive protein (hsCRP) can serve as predictive biomarkers for obesity-related cancers in patients recently diagnosed with T2D.
- They identified patients with recent-onset T2D and no prior history of cancer participating in the ongoing Danish Centre for Strategic Research in Type 2 Diabetes cohort study.
- At study initiation, plasma levels of IL-6 and TNF-alpha were measured using Meso Scale Discovery assays, and serum levels of hsCRP were measured using immunofluorometric assays.
TAKEAWAY:
- Among 6,466 eligible patients (40.5% women; median age, 60.9 years), 327 developed obesity-related cancers over a median follow-up of 8.8 years.
- Each SD increase in log-transformed IL-6 levels increased the risk for obesity-related cancers by 19%.
- The researchers did not find a strong association between TNF-alpha or hsCRP and obesity-related cancers.
- The addition of baseline IL-6 levels to other well-known risk factors for obesity-related cancers improved the performance of a cancer prediction model from 0.685 to 0.693, translating to a small but important increase in the ability to predict whether an individual would develop one of these cancers.
IN PRACTICE:
“In future, a simple blood test could identify those at higher risk of the cancers,” said the study’s lead author in an accompanying press release.
SOURCE:
The study was led by Mathilde D. Bennetsen, Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark, and published online on August 27 as an early release from the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.
LIMITATIONS:
No limitations were discussed in this abstract. However, the reliance on registry data may have introduced potential biases related to data accuracy and completeness.
DISCLOSURES:
The Danish Centre for Strategic Research in Type 2 Diabetes was supported by grants from the Danish Agency for Science and the Novo Nordisk Foundation. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
potentially enabling the identification of higher-risk individuals through a simple blood test.
METHODOLOGY:
- T2D is associated with an increased risk for obesity-related cancers, including breast, renal, uterine, thyroid, ovarian, and gastrointestinal cancers, as well as multiple myeloma, possibly because of chronic low-grade inflammation.
- Researchers explored whether the markers of inflammation IL-6, tumor necrosis factor alpha (TNF-alpha), and high-sensitivity C-reactive protein (hsCRP) can serve as predictive biomarkers for obesity-related cancers in patients recently diagnosed with T2D.
- They identified patients with recent-onset T2D and no prior history of cancer participating in the ongoing Danish Centre for Strategic Research in Type 2 Diabetes cohort study.
- At study initiation, plasma levels of IL-6 and TNF-alpha were measured using Meso Scale Discovery assays, and serum levels of hsCRP were measured using immunofluorometric assays.
TAKEAWAY:
- Among 6,466 eligible patients (40.5% women; median age, 60.9 years), 327 developed obesity-related cancers over a median follow-up of 8.8 years.
- Each SD increase in log-transformed IL-6 levels increased the risk for obesity-related cancers by 19%.
- The researchers did not find a strong association between TNF-alpha or hsCRP and obesity-related cancers.
- The addition of baseline IL-6 levels to other well-known risk factors for obesity-related cancers improved the performance of a cancer prediction model from 0.685 to 0.693, translating to a small but important increase in the ability to predict whether an individual would develop one of these cancers.
IN PRACTICE:
“In future, a simple blood test could identify those at higher risk of the cancers,” said the study’s lead author in an accompanying press release.
SOURCE:
The study was led by Mathilde D. Bennetsen, Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark, and published online on August 27 as an early release from the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.
LIMITATIONS:
No limitations were discussed in this abstract. However, the reliance on registry data may have introduced potential biases related to data accuracy and completeness.
DISCLOSURES:
The Danish Centre for Strategic Research in Type 2 Diabetes was supported by grants from the Danish Agency for Science and the Novo Nordisk Foundation. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Monitor Asthma Patients on Biologics for Remission, Potential EGPA Symptoms During Steroid Tapering
VIENNA — , according to pulmonary experts presenting at the European Respiratory Society (ERS) 2024 International Congress.
Biologics have revolutionized the treatment of severe asthma, significantly improving patient outcomes. However, the focus has recently shifted toward achieving more comprehensive disease control. Remission, already a well-established goal in conditions like rheumatoid arthritis and inflammatory bowel disease, is now being explored in patients with asthma receiving biologics.
Peter Howarth, medical director at Global Medical, Specialty Medicine, GSK, in Brentford, England, said that new clinical remission criteria in asthma may be overly rigid and of little use. He said that more attainable limits must be created. Meanwhile, clinicians should collect clinical data more thoroughly.
In parallel, studies have also raised questions about the role of biologics in the emergence of EGPA.
Defining Clinical Remission in Asthma
Last year, a working group, including members from the American Thoracic Society and the American College and Academy of Allergy, Asthma, and Immunology, proposed new guidelines to define clinical remission in asthma. These guidelines extended beyond the typical outcomes of no severe exacerbations, no maintenance oral corticosteroid use, good asthma control, and stable lung function. The additional recommendations included no missed work or school due to asthma, limited use of rescue medication (no more than once a month), and reduced inhaled corticosteroid use to low or medium doses.
To explore the feasibility of achieving these clinical remission outcomes, GSK partnered with the Mayo Clinic for a retrospective analysis of the medical records of 700 patients with asthma undergoing various biologic therapies. The study revealed that essential data for determining clinical remission, such as asthma control and exacerbation records, were inconsistently documented. While some data were recorded, such as maintenance corticosteroid use in 50%-60% of cases, other key measures, like asthma control, were recorded in less than a quarter of the patients.
GSK researchers analyzed available data and found that around 30% of patients on any biologic therapy met three components of remission. Mepolizumab performed better than other corticosteroids, with over 40% of those receiving the drug meeting these criteria. However, when stricter definitions were applied, such as requiring four or more remission components, fewer patients achieved remission — less than 10% for four components, with no patients meeting the full seven-point criteria proposed by the working group.
An ongoing ERS Task Force is now exploring what clinical remission outcomes are practical to achieve, as the current definitions may be too aspirational, said Mr. Howarth. “It’s a matter of defying what is practical to achieve because if you can’t achieve it, then it won’t be valuable.”
He also pointed out that biologics are often used for the most severe cases of asthma after other treatments have failed. Evidence suggests that introducing biologics earlier in the disease, before chronic damage occurs, may result in better patient outcomes.
Biologics and EGPA
In a retrospective study, clinical details of 27 patients with adult-onset asthma from 28 countries, all on biologic therapy, were analyzed. The study, a multicounty collaboration, was led by ERS Severe Heterogeneous Asthma Research Collaboration, Patient-centred (SHARP), and aimed to understand the role of biologics in the emergence of EGPA.
The most significant finding presented at the ERS 2024 International Congress was that EGPA was not associated with maintenance corticosteroids; instead, it often emerged when corticosteroid doses were reduced or tapered off. “This might suggest that steroid withdrawal may unmask the underlying disease,” said Hitasha Rupani, MD, a consultant respiratory physician at the University Hospital Southampton, in Southampton, England. Importantly, the rate at which steroids were tapered did not influence the onset of EGPA, indicating that the tapering process, rather than its speed, may be the critical factor. However, due to the small sample size, this remains a hypothesis, Dr. Rupani explained.
The study also found that when clinicians had a clinical suspicion of EGPA before starting biologic therapy, the diagnosis was made earlier than in cases without such suspicion. Dr. Rupani concluded that this underscores the importance of clinical vigilance and the need to monitor patients closely for EGPA symptoms, especially during corticosteroid tapering.
The study was funded by GSK. Mr. Howarth is an employee at GSK. Dr. Rupani reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
VIENNA — , according to pulmonary experts presenting at the European Respiratory Society (ERS) 2024 International Congress.
Biologics have revolutionized the treatment of severe asthma, significantly improving patient outcomes. However, the focus has recently shifted toward achieving more comprehensive disease control. Remission, already a well-established goal in conditions like rheumatoid arthritis and inflammatory bowel disease, is now being explored in patients with asthma receiving biologics.
Peter Howarth, medical director at Global Medical, Specialty Medicine, GSK, in Brentford, England, said that new clinical remission criteria in asthma may be overly rigid and of little use. He said that more attainable limits must be created. Meanwhile, clinicians should collect clinical data more thoroughly.
In parallel, studies have also raised questions about the role of biologics in the emergence of EGPA.
Defining Clinical Remission in Asthma
Last year, a working group, including members from the American Thoracic Society and the American College and Academy of Allergy, Asthma, and Immunology, proposed new guidelines to define clinical remission in asthma. These guidelines extended beyond the typical outcomes of no severe exacerbations, no maintenance oral corticosteroid use, good asthma control, and stable lung function. The additional recommendations included no missed work or school due to asthma, limited use of rescue medication (no more than once a month), and reduced inhaled corticosteroid use to low or medium doses.
To explore the feasibility of achieving these clinical remission outcomes, GSK partnered with the Mayo Clinic for a retrospective analysis of the medical records of 700 patients with asthma undergoing various biologic therapies. The study revealed that essential data for determining clinical remission, such as asthma control and exacerbation records, were inconsistently documented. While some data were recorded, such as maintenance corticosteroid use in 50%-60% of cases, other key measures, like asthma control, were recorded in less than a quarter of the patients.
GSK researchers analyzed available data and found that around 30% of patients on any biologic therapy met three components of remission. Mepolizumab performed better than other corticosteroids, with over 40% of those receiving the drug meeting these criteria. However, when stricter definitions were applied, such as requiring four or more remission components, fewer patients achieved remission — less than 10% for four components, with no patients meeting the full seven-point criteria proposed by the working group.
An ongoing ERS Task Force is now exploring what clinical remission outcomes are practical to achieve, as the current definitions may be too aspirational, said Mr. Howarth. “It’s a matter of defying what is practical to achieve because if you can’t achieve it, then it won’t be valuable.”
He also pointed out that biologics are often used for the most severe cases of asthma after other treatments have failed. Evidence suggests that introducing biologics earlier in the disease, before chronic damage occurs, may result in better patient outcomes.
Biologics and EGPA
In a retrospective study, clinical details of 27 patients with adult-onset asthma from 28 countries, all on biologic therapy, were analyzed. The study, a multicounty collaboration, was led by ERS Severe Heterogeneous Asthma Research Collaboration, Patient-centred (SHARP), and aimed to understand the role of biologics in the emergence of EGPA.
The most significant finding presented at the ERS 2024 International Congress was that EGPA was not associated with maintenance corticosteroids; instead, it often emerged when corticosteroid doses were reduced or tapered off. “This might suggest that steroid withdrawal may unmask the underlying disease,” said Hitasha Rupani, MD, a consultant respiratory physician at the University Hospital Southampton, in Southampton, England. Importantly, the rate at which steroids were tapered did not influence the onset of EGPA, indicating that the tapering process, rather than its speed, may be the critical factor. However, due to the small sample size, this remains a hypothesis, Dr. Rupani explained.
The study also found that when clinicians had a clinical suspicion of EGPA before starting biologic therapy, the diagnosis was made earlier than in cases without such suspicion. Dr. Rupani concluded that this underscores the importance of clinical vigilance and the need to monitor patients closely for EGPA symptoms, especially during corticosteroid tapering.
The study was funded by GSK. Mr. Howarth is an employee at GSK. Dr. Rupani reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
VIENNA — , according to pulmonary experts presenting at the European Respiratory Society (ERS) 2024 International Congress.
Biologics have revolutionized the treatment of severe asthma, significantly improving patient outcomes. However, the focus has recently shifted toward achieving more comprehensive disease control. Remission, already a well-established goal in conditions like rheumatoid arthritis and inflammatory bowel disease, is now being explored in patients with asthma receiving biologics.
Peter Howarth, medical director at Global Medical, Specialty Medicine, GSK, in Brentford, England, said that new clinical remission criteria in asthma may be overly rigid and of little use. He said that more attainable limits must be created. Meanwhile, clinicians should collect clinical data more thoroughly.
In parallel, studies have also raised questions about the role of biologics in the emergence of EGPA.
Defining Clinical Remission in Asthma
Last year, a working group, including members from the American Thoracic Society and the American College and Academy of Allergy, Asthma, and Immunology, proposed new guidelines to define clinical remission in asthma. These guidelines extended beyond the typical outcomes of no severe exacerbations, no maintenance oral corticosteroid use, good asthma control, and stable lung function. The additional recommendations included no missed work or school due to asthma, limited use of rescue medication (no more than once a month), and reduced inhaled corticosteroid use to low or medium doses.
To explore the feasibility of achieving these clinical remission outcomes, GSK partnered with the Mayo Clinic for a retrospective analysis of the medical records of 700 patients with asthma undergoing various biologic therapies. The study revealed that essential data for determining clinical remission, such as asthma control and exacerbation records, were inconsistently documented. While some data were recorded, such as maintenance corticosteroid use in 50%-60% of cases, other key measures, like asthma control, were recorded in less than a quarter of the patients.
GSK researchers analyzed available data and found that around 30% of patients on any biologic therapy met three components of remission. Mepolizumab performed better than other corticosteroids, with over 40% of those receiving the drug meeting these criteria. However, when stricter definitions were applied, such as requiring four or more remission components, fewer patients achieved remission — less than 10% for four components, with no patients meeting the full seven-point criteria proposed by the working group.
An ongoing ERS Task Force is now exploring what clinical remission outcomes are practical to achieve, as the current definitions may be too aspirational, said Mr. Howarth. “It’s a matter of defying what is practical to achieve because if you can’t achieve it, then it won’t be valuable.”
He also pointed out that biologics are often used for the most severe cases of asthma after other treatments have failed. Evidence suggests that introducing biologics earlier in the disease, before chronic damage occurs, may result in better patient outcomes.
Biologics and EGPA
In a retrospective study, clinical details of 27 patients with adult-onset asthma from 28 countries, all on biologic therapy, were analyzed. The study, a multicounty collaboration, was led by ERS Severe Heterogeneous Asthma Research Collaboration, Patient-centred (SHARP), and aimed to understand the role of biologics in the emergence of EGPA.
The most significant finding presented at the ERS 2024 International Congress was that EGPA was not associated with maintenance corticosteroids; instead, it often emerged when corticosteroid doses were reduced or tapered off. “This might suggest that steroid withdrawal may unmask the underlying disease,” said Hitasha Rupani, MD, a consultant respiratory physician at the University Hospital Southampton, in Southampton, England. Importantly, the rate at which steroids were tapered did not influence the onset of EGPA, indicating that the tapering process, rather than its speed, may be the critical factor. However, due to the small sample size, this remains a hypothesis, Dr. Rupani explained.
The study also found that when clinicians had a clinical suspicion of EGPA before starting biologic therapy, the diagnosis was made earlier than in cases without such suspicion. Dr. Rupani concluded that this underscores the importance of clinical vigilance and the need to monitor patients closely for EGPA symptoms, especially during corticosteroid tapering.
The study was funded by GSK. Mr. Howarth is an employee at GSK. Dr. Rupani reports no relevant financial relationships.
A version of this article appeared on Medscape.com.