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ZUMA-5: Axi-cel yields high response rate in indolent NHL
, according to phase 2 study results presented at the annual meeting of the American Society of Hematology, held virtually this year.
The overall response rate exceeded 90% in the ZUMA-5 study, which included patients with multiply relapsed follicular lymphoma (FL) or marginal zone lymphoma (MZL) who were treated with this anti-CD19 chimeric antigen receptor (CAR) T cell therapy.
“Although longer follow-up is needed, these responses appear to be durable,” said investigator Caron Jacobson, MD, of Dana-Farber Cancer Institute in Boston.
Complete responses (CRs) after axi-cel treatment were seen in about three-quarters of patients, and most of those patients were still in response with a median follow-up that approached 1.5 years as of this report at the ASH meeting.
In her presentation, Dr. Jacobson said the safety profile of axi-cel in ZUMA-5 was manageable and “at least similar” to what was previously seen in aggressive relapsed lymphomas, referring to the ZUMA-1 study that led to 2017 approval by the Food and Drug Administration of the treatment for relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy.
The FL patient cohort in ZUMA-5 appeared to have lower rates of cytokine release syndrome (CRS) and high-grade neurotoxicity, compared with the MZL cohort in the study, she added.
Catherine Bollard, MD, of Children’s National Research Institute in Washington, said these results suggest axi-cel may be a “viable treatment option” for some patients with indolent lymphomas who have not responded to other therapies.
“What the field does need is long-term follow-up in the real-world setting to see what the true progression-free and disease-free survival is for these patients,” said Dr. Bollard, who moderated a media briefing that included the ZUMA-5 study.
“It’s really exciting to see this data in the [indolent] lymphoma setting, and I actually would like to see it moved further up in the treatment of patients, earlier in their disease process, if that’s going to be possible,” she added.
Promising results
The report on ZUMA-5, presented by Dr. Jacobson, involved 146 patients with relapsed/refractory indolent NHL: 124 patients with FL and an exploratory cohort of 22 patients with MZL. All patients had received at least two prior lines of therapy.
Following a fludarabine/cyclophosphamide conditioning regimen, patients received axi-cel at the FDA-approved dose of 2 x 106 CAR-positive T cells per kg of body weight. The primary endpoint of the study was overall response rate (ORR).
For 104 patients evaluable for efficacy, the ORR was 92% (96 patients), including CR in 76% (79 patients), data show. Among 84 FL patients evaluable for efficacy, ORR and CR were 94% (79 patients) and 80% (67 patients), respectively, while among 20 evaluable patients in the exploratory MZL cohort, ORR and CR were 60% (12 patients) and 25% (5 patients), respectively.
Sixty-four percent of patients with FL had an ongoing response at a median follow-up of 17.5 months, according to Dr. Jacobson, who added that median duration of response (DOR) had not been reached, while the 12-month DOR rate approached 72%.
The 12-month progression-free survival and overall survival rates were 73.7% and 92.9%, respectively, with medians not yet reached for either survival outcome, according to reported data.
Adverse effects
The incidence of grade 3 or greater neurologic events was lower in FL patients (15%), compared with MZL patients (41%), according to Dr. Jacobson.
While CRS occurred in 82% of patients, rates of grade 3 or greater CRS occurred in just 6% of FL patients and 9% of MZL patients, the investigator said.
There were no grade 5 neurologic events, and one grade 5 CRS was observed, she noted in her presentation.
The median time to onset of CRS was 4 days, compared with 2 days in the ZUMA-1 trial. “This may have implications for the possibility of outpatient therapy,” she said.
A study is planned to look at outpatient administration of axi-cel in patients with indolent NHL, she added.
Dr. Jacobson said she had no conflicts of interest to declare. Coauthors reported disclosures related to Kite, a Gilead Company; Genentech; Epizyme; Verastem; Novartis; and Pfizer, among others.
Correction, 12/7/20: An earlier version of this article misattributed some aspects of the ZUMA-5 trial to ZUMA-1.
SOURCE: Jacobson CA et al. ASH 2020, Abstract 700.
, according to phase 2 study results presented at the annual meeting of the American Society of Hematology, held virtually this year.
The overall response rate exceeded 90% in the ZUMA-5 study, which included patients with multiply relapsed follicular lymphoma (FL) or marginal zone lymphoma (MZL) who were treated with this anti-CD19 chimeric antigen receptor (CAR) T cell therapy.
“Although longer follow-up is needed, these responses appear to be durable,” said investigator Caron Jacobson, MD, of Dana-Farber Cancer Institute in Boston.
Complete responses (CRs) after axi-cel treatment were seen in about three-quarters of patients, and most of those patients were still in response with a median follow-up that approached 1.5 years as of this report at the ASH meeting.
In her presentation, Dr. Jacobson said the safety profile of axi-cel in ZUMA-5 was manageable and “at least similar” to what was previously seen in aggressive relapsed lymphomas, referring to the ZUMA-1 study that led to 2017 approval by the Food and Drug Administration of the treatment for relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy.
The FL patient cohort in ZUMA-5 appeared to have lower rates of cytokine release syndrome (CRS) and high-grade neurotoxicity, compared with the MZL cohort in the study, she added.
Catherine Bollard, MD, of Children’s National Research Institute in Washington, said these results suggest axi-cel may be a “viable treatment option” for some patients with indolent lymphomas who have not responded to other therapies.
“What the field does need is long-term follow-up in the real-world setting to see what the true progression-free and disease-free survival is for these patients,” said Dr. Bollard, who moderated a media briefing that included the ZUMA-5 study.
“It’s really exciting to see this data in the [indolent] lymphoma setting, and I actually would like to see it moved further up in the treatment of patients, earlier in their disease process, if that’s going to be possible,” she added.
Promising results
The report on ZUMA-5, presented by Dr. Jacobson, involved 146 patients with relapsed/refractory indolent NHL: 124 patients with FL and an exploratory cohort of 22 patients with MZL. All patients had received at least two prior lines of therapy.
Following a fludarabine/cyclophosphamide conditioning regimen, patients received axi-cel at the FDA-approved dose of 2 x 106 CAR-positive T cells per kg of body weight. The primary endpoint of the study was overall response rate (ORR).
For 104 patients evaluable for efficacy, the ORR was 92% (96 patients), including CR in 76% (79 patients), data show. Among 84 FL patients evaluable for efficacy, ORR and CR were 94% (79 patients) and 80% (67 patients), respectively, while among 20 evaluable patients in the exploratory MZL cohort, ORR and CR were 60% (12 patients) and 25% (5 patients), respectively.
Sixty-four percent of patients with FL had an ongoing response at a median follow-up of 17.5 months, according to Dr. Jacobson, who added that median duration of response (DOR) had not been reached, while the 12-month DOR rate approached 72%.
The 12-month progression-free survival and overall survival rates were 73.7% and 92.9%, respectively, with medians not yet reached for either survival outcome, according to reported data.
Adverse effects
The incidence of grade 3 or greater neurologic events was lower in FL patients (15%), compared with MZL patients (41%), according to Dr. Jacobson.
While CRS occurred in 82% of patients, rates of grade 3 or greater CRS occurred in just 6% of FL patients and 9% of MZL patients, the investigator said.
There were no grade 5 neurologic events, and one grade 5 CRS was observed, she noted in her presentation.
The median time to onset of CRS was 4 days, compared with 2 days in the ZUMA-1 trial. “This may have implications for the possibility of outpatient therapy,” she said.
A study is planned to look at outpatient administration of axi-cel in patients with indolent NHL, she added.
Dr. Jacobson said she had no conflicts of interest to declare. Coauthors reported disclosures related to Kite, a Gilead Company; Genentech; Epizyme; Verastem; Novartis; and Pfizer, among others.
Correction, 12/7/20: An earlier version of this article misattributed some aspects of the ZUMA-5 trial to ZUMA-1.
SOURCE: Jacobson CA et al. ASH 2020, Abstract 700.
, according to phase 2 study results presented at the annual meeting of the American Society of Hematology, held virtually this year.
The overall response rate exceeded 90% in the ZUMA-5 study, which included patients with multiply relapsed follicular lymphoma (FL) or marginal zone lymphoma (MZL) who were treated with this anti-CD19 chimeric antigen receptor (CAR) T cell therapy.
“Although longer follow-up is needed, these responses appear to be durable,” said investigator Caron Jacobson, MD, of Dana-Farber Cancer Institute in Boston.
Complete responses (CRs) after axi-cel treatment were seen in about three-quarters of patients, and most of those patients were still in response with a median follow-up that approached 1.5 years as of this report at the ASH meeting.
In her presentation, Dr. Jacobson said the safety profile of axi-cel in ZUMA-5 was manageable and “at least similar” to what was previously seen in aggressive relapsed lymphomas, referring to the ZUMA-1 study that led to 2017 approval by the Food and Drug Administration of the treatment for relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy.
The FL patient cohort in ZUMA-5 appeared to have lower rates of cytokine release syndrome (CRS) and high-grade neurotoxicity, compared with the MZL cohort in the study, she added.
Catherine Bollard, MD, of Children’s National Research Institute in Washington, said these results suggest axi-cel may be a “viable treatment option” for some patients with indolent lymphomas who have not responded to other therapies.
“What the field does need is long-term follow-up in the real-world setting to see what the true progression-free and disease-free survival is for these patients,” said Dr. Bollard, who moderated a media briefing that included the ZUMA-5 study.
“It’s really exciting to see this data in the [indolent] lymphoma setting, and I actually would like to see it moved further up in the treatment of patients, earlier in their disease process, if that’s going to be possible,” she added.
Promising results
The report on ZUMA-5, presented by Dr. Jacobson, involved 146 patients with relapsed/refractory indolent NHL: 124 patients with FL and an exploratory cohort of 22 patients with MZL. All patients had received at least two prior lines of therapy.
Following a fludarabine/cyclophosphamide conditioning regimen, patients received axi-cel at the FDA-approved dose of 2 x 106 CAR-positive T cells per kg of body weight. The primary endpoint of the study was overall response rate (ORR).
For 104 patients evaluable for efficacy, the ORR was 92% (96 patients), including CR in 76% (79 patients), data show. Among 84 FL patients evaluable for efficacy, ORR and CR were 94% (79 patients) and 80% (67 patients), respectively, while among 20 evaluable patients in the exploratory MZL cohort, ORR and CR were 60% (12 patients) and 25% (5 patients), respectively.
Sixty-four percent of patients with FL had an ongoing response at a median follow-up of 17.5 months, according to Dr. Jacobson, who added that median duration of response (DOR) had not been reached, while the 12-month DOR rate approached 72%.
The 12-month progression-free survival and overall survival rates were 73.7% and 92.9%, respectively, with medians not yet reached for either survival outcome, according to reported data.
Adverse effects
The incidence of grade 3 or greater neurologic events was lower in FL patients (15%), compared with MZL patients (41%), according to Dr. Jacobson.
While CRS occurred in 82% of patients, rates of grade 3 or greater CRS occurred in just 6% of FL patients and 9% of MZL patients, the investigator said.
There were no grade 5 neurologic events, and one grade 5 CRS was observed, she noted in her presentation.
The median time to onset of CRS was 4 days, compared with 2 days in the ZUMA-1 trial. “This may have implications for the possibility of outpatient therapy,” she said.
A study is planned to look at outpatient administration of axi-cel in patients with indolent NHL, she added.
Dr. Jacobson said she had no conflicts of interest to declare. Coauthors reported disclosures related to Kite, a Gilead Company; Genentech; Epizyme; Verastem; Novartis; and Pfizer, among others.
Correction, 12/7/20: An earlier version of this article misattributed some aspects of the ZUMA-5 trial to ZUMA-1.
SOURCE: Jacobson CA et al. ASH 2020, Abstract 700.
FROM ASH 2020
COVID-19–related outcomes poor for patients with hematologic disease in ASH registry
Patients with hematologic disease who develop COVID-19 may experience substantial morbidity and mortality related to SARS-CoV-2 infection, according to recent registry data reported at the all-virtual annual meeting of the American Society of Hematology.
Overall mortality was 28% for the first 250 patients entered into the ASH Research Collaborative COVID-19 Registry for Hematology, researchers reported in an abstract of their study findings.
However, the burden of death and moderate-to-severe COVID-19 outcomes was highest in patients with poorer prognosis and those with relapsed/refractory hematological disease, they added.
The most commonly represented malignancies were acute leukemia, non-Hodgkin lymphoma, and myeloma or amyloidosis, according to the report.
Taken together, the findings do support an “emerging consensus” that COVID-19 related morbidity and mortality is significant in these patients, authors said – however, the current findings may not be reason enough to support a change in treatment course for the underlying disease.
“We see no reason, based on our data, to withhold intensive therapies from patients with underlying hematologic malignancies and favorable prognoses, if aggressive supportive care is consistent with patient preferences,” wrote the researchers.
ASH President Stephanie Lee, MD, MPH, said these registry findings are important to better understand how SARS-CoV-2 is affecting not only patients with hematologic diseases, but also individuals who experience COVID-19-related hematologic complications.
However, the findings are limited due to the heterogeneity of diseases, symptoms, and treatments represented in the registry, said Dr. Lee, associate director of the clinical research division at Fred Hutchinson Cancer Center in Seattle.
“More data will be coming in, but I think this is an example of trying to harness real-world information to try to learn things until we get more controlled studies,” Dr. Lee said in a media briefing held in advance of the ASH meeting.
Comorbidities and more
Patients with blood cancers are often older and may have comorbidities such as diabetes or hypertension that have been linked to poor COVID-19 outcomes, according to the authors of the report, led by William A. Wood, MD, MPH, associate professor of medicine with the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, N.C.
Moreover, these patients may have underlying immune dysfunction and may receive chemotherapy or immunotherapy that is “profoundly immunosuppressive,” Dr. Wood and coauthors said in their report.
To date, however, risks of morbidity and mortality related to SARS-CoV-2 infection have not been well defined in this patient population, authors said.
More data is emerging now from the ASH Research Collaborative COVID-19 Registry for Hematology, which includes data on patients positive for COVID-19 who have a past or present hematologic condition or have experienced a hematologic complication related to COVID-19.
All data from the registry is being made available through a dashboard on the ASH Research Collaborative website, which as of Dec. 1, 2020, included 693 complete cases.
The data cut in the ASH abstract includes the first 250 patients enrolled at 74 sites around the world, the authors said. The most common malignancies included acute leukemia in 33%, non-Hodgkin lymphoma in 27%, and myeloma or amyloidosis in 16%.
The most frequently reported symptoms included fever in 73%, cough in 67%, dyspnea in 50%, and fatigue in 40%, according to that report.
At the time of this data snapshot, treatment with COVID-19-directed therapies including hydroxychloroquine or azithromycin were common, reported in 76 and 59 patients, respectively, in the cohort.
Batch submissions from sites with high incidence of COVID-19 infection are ongoing. The registry has been expanded to include nonmalignant hematologic diseases, and the registry will continue to accumulate data as a resource for the hematology community.
Overall mortality was 28% at the time, according to the abstract, with nearly all of the deaths occurring in patients classified as having COVID-19 that was moderate (i.e., requiring hospitalization) or severe (i.e., requiring ICU admission).
“In some instances, death occurred after a decision was made to forgo ICU admission in favor of a palliative approach,” said Dr. Wood and coauthors in their report.
Dr. Wood reported research funding from Pfizer, consultancy with Teladoc/Best Doctors, and honoraria from the ASH Research Collaborative. Coauthors provided disclosures related to Celgene, Madrigal Pharmaceuticals, Pharmacyclics, and Amgen, among others.
SOURCE: Wood WA et al. ASH 2020, Abstract 215.
Patients with hematologic disease who develop COVID-19 may experience substantial morbidity and mortality related to SARS-CoV-2 infection, according to recent registry data reported at the all-virtual annual meeting of the American Society of Hematology.
Overall mortality was 28% for the first 250 patients entered into the ASH Research Collaborative COVID-19 Registry for Hematology, researchers reported in an abstract of their study findings.
However, the burden of death and moderate-to-severe COVID-19 outcomes was highest in patients with poorer prognosis and those with relapsed/refractory hematological disease, they added.
The most commonly represented malignancies were acute leukemia, non-Hodgkin lymphoma, and myeloma or amyloidosis, according to the report.
Taken together, the findings do support an “emerging consensus” that COVID-19 related morbidity and mortality is significant in these patients, authors said – however, the current findings may not be reason enough to support a change in treatment course for the underlying disease.
“We see no reason, based on our data, to withhold intensive therapies from patients with underlying hematologic malignancies and favorable prognoses, if aggressive supportive care is consistent with patient preferences,” wrote the researchers.
ASH President Stephanie Lee, MD, MPH, said these registry findings are important to better understand how SARS-CoV-2 is affecting not only patients with hematologic diseases, but also individuals who experience COVID-19-related hematologic complications.
However, the findings are limited due to the heterogeneity of diseases, symptoms, and treatments represented in the registry, said Dr. Lee, associate director of the clinical research division at Fred Hutchinson Cancer Center in Seattle.
“More data will be coming in, but I think this is an example of trying to harness real-world information to try to learn things until we get more controlled studies,” Dr. Lee said in a media briefing held in advance of the ASH meeting.
Comorbidities and more
Patients with blood cancers are often older and may have comorbidities such as diabetes or hypertension that have been linked to poor COVID-19 outcomes, according to the authors of the report, led by William A. Wood, MD, MPH, associate professor of medicine with the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, N.C.
Moreover, these patients may have underlying immune dysfunction and may receive chemotherapy or immunotherapy that is “profoundly immunosuppressive,” Dr. Wood and coauthors said in their report.
To date, however, risks of morbidity and mortality related to SARS-CoV-2 infection have not been well defined in this patient population, authors said.
More data is emerging now from the ASH Research Collaborative COVID-19 Registry for Hematology, which includes data on patients positive for COVID-19 who have a past or present hematologic condition or have experienced a hematologic complication related to COVID-19.
All data from the registry is being made available through a dashboard on the ASH Research Collaborative website, which as of Dec. 1, 2020, included 693 complete cases.
The data cut in the ASH abstract includes the first 250 patients enrolled at 74 sites around the world, the authors said. The most common malignancies included acute leukemia in 33%, non-Hodgkin lymphoma in 27%, and myeloma or amyloidosis in 16%.
The most frequently reported symptoms included fever in 73%, cough in 67%, dyspnea in 50%, and fatigue in 40%, according to that report.
At the time of this data snapshot, treatment with COVID-19-directed therapies including hydroxychloroquine or azithromycin were common, reported in 76 and 59 patients, respectively, in the cohort.
Batch submissions from sites with high incidence of COVID-19 infection are ongoing. The registry has been expanded to include nonmalignant hematologic diseases, and the registry will continue to accumulate data as a resource for the hematology community.
Overall mortality was 28% at the time, according to the abstract, with nearly all of the deaths occurring in patients classified as having COVID-19 that was moderate (i.e., requiring hospitalization) or severe (i.e., requiring ICU admission).
“In some instances, death occurred after a decision was made to forgo ICU admission in favor of a palliative approach,” said Dr. Wood and coauthors in their report.
Dr. Wood reported research funding from Pfizer, consultancy with Teladoc/Best Doctors, and honoraria from the ASH Research Collaborative. Coauthors provided disclosures related to Celgene, Madrigal Pharmaceuticals, Pharmacyclics, and Amgen, among others.
SOURCE: Wood WA et al. ASH 2020, Abstract 215.
Patients with hematologic disease who develop COVID-19 may experience substantial morbidity and mortality related to SARS-CoV-2 infection, according to recent registry data reported at the all-virtual annual meeting of the American Society of Hematology.
Overall mortality was 28% for the first 250 patients entered into the ASH Research Collaborative COVID-19 Registry for Hematology, researchers reported in an abstract of their study findings.
However, the burden of death and moderate-to-severe COVID-19 outcomes was highest in patients with poorer prognosis and those with relapsed/refractory hematological disease, they added.
The most commonly represented malignancies were acute leukemia, non-Hodgkin lymphoma, and myeloma or amyloidosis, according to the report.
Taken together, the findings do support an “emerging consensus” that COVID-19 related morbidity and mortality is significant in these patients, authors said – however, the current findings may not be reason enough to support a change in treatment course for the underlying disease.
“We see no reason, based on our data, to withhold intensive therapies from patients with underlying hematologic malignancies and favorable prognoses, if aggressive supportive care is consistent with patient preferences,” wrote the researchers.
ASH President Stephanie Lee, MD, MPH, said these registry findings are important to better understand how SARS-CoV-2 is affecting not only patients with hematologic diseases, but also individuals who experience COVID-19-related hematologic complications.
However, the findings are limited due to the heterogeneity of diseases, symptoms, and treatments represented in the registry, said Dr. Lee, associate director of the clinical research division at Fred Hutchinson Cancer Center in Seattle.
“More data will be coming in, but I think this is an example of trying to harness real-world information to try to learn things until we get more controlled studies,” Dr. Lee said in a media briefing held in advance of the ASH meeting.
Comorbidities and more
Patients with blood cancers are often older and may have comorbidities such as diabetes or hypertension that have been linked to poor COVID-19 outcomes, according to the authors of the report, led by William A. Wood, MD, MPH, associate professor of medicine with the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, N.C.
Moreover, these patients may have underlying immune dysfunction and may receive chemotherapy or immunotherapy that is “profoundly immunosuppressive,” Dr. Wood and coauthors said in their report.
To date, however, risks of morbidity and mortality related to SARS-CoV-2 infection have not been well defined in this patient population, authors said.
More data is emerging now from the ASH Research Collaborative COVID-19 Registry for Hematology, which includes data on patients positive for COVID-19 who have a past or present hematologic condition or have experienced a hematologic complication related to COVID-19.
All data from the registry is being made available through a dashboard on the ASH Research Collaborative website, which as of Dec. 1, 2020, included 693 complete cases.
The data cut in the ASH abstract includes the first 250 patients enrolled at 74 sites around the world, the authors said. The most common malignancies included acute leukemia in 33%, non-Hodgkin lymphoma in 27%, and myeloma or amyloidosis in 16%.
The most frequently reported symptoms included fever in 73%, cough in 67%, dyspnea in 50%, and fatigue in 40%, according to that report.
At the time of this data snapshot, treatment with COVID-19-directed therapies including hydroxychloroquine or azithromycin were common, reported in 76 and 59 patients, respectively, in the cohort.
Batch submissions from sites with high incidence of COVID-19 infection are ongoing. The registry has been expanded to include nonmalignant hematologic diseases, and the registry will continue to accumulate data as a resource for the hematology community.
Overall mortality was 28% at the time, according to the abstract, with nearly all of the deaths occurring in patients classified as having COVID-19 that was moderate (i.e., requiring hospitalization) or severe (i.e., requiring ICU admission).
“In some instances, death occurred after a decision was made to forgo ICU admission in favor of a palliative approach,” said Dr. Wood and coauthors in their report.
Dr. Wood reported research funding from Pfizer, consultancy with Teladoc/Best Doctors, and honoraria from the ASH Research Collaborative. Coauthors provided disclosures related to Celgene, Madrigal Pharmaceuticals, Pharmacyclics, and Amgen, among others.
SOURCE: Wood WA et al. ASH 2020, Abstract 215.
FROM ASH 2020
Infant’s COVID-19–related myocardial injury reversed
Reports of signs of heart failure in adults with COVID-19 have been rare – just four such cases have been published since the outbreak started in China – and now a team of pediatric cardiologists in New York have reported a case of acute but reversible myocardial injury in an infant with COVID-19.
and right upper lobe atelectasis.
The 2-month-old infant went home after more than 2 weeks in the hospital with no apparent lingering cardiac effects of the illness and not needing any oral heart failure medications, Madhu Sharma, MD, of the Children’s Hospital and Montefiore in New York and colleagues reported in JACC Case Reports. With close follow-up, the child’s left ventricle size and systolic function have remained normal and mitral regurgitation resolved. The case report didn’t mention the infant’s gender.
But before the straightforward postdischarge course emerged, the infant was in a precarious state, and Dr. Sharma and her team were challenged to diagnose the underlying causes.
The child, who was born about 7 weeks premature, first came to the hospital having turned blue after choking on food. Nonrebreather mask ventilation was initiated in the ED, and an examination detected a holosystolic murmur. A test for COVID-19 was negative, but a later test was positive, and a chest x-ray exhibited cardiomegaly and signs of fluid and inflammation in the lungs.
An electrocardiogram detected sinus tachycardia, ST-segment depression and other anomalies in cardiac function. Further investigation with a transthoracic ECG showed severely depressed left ventricle systolic function with an ejection fraction of 30%, severe mitral regurgitation, and normal right ventricular systolic function.
Treatment included remdesivir and intravenous antibiotics. Through the hospital course, the patient was extubated to noninvasive ventilation, reintubated, put on intravenous steroid (methylprednisolone) and low-molecular-weight heparin, extubated, and tested throughout for cardiac function.
By day 14, left ventricle size and function normalized, and while the mitral regurgitation remained severe, it improved later without HF therapies. Left ventricle ejection fraction had recovered to 60%, and key cardiac biomarkers had normalized. On day 16, milrinone was discontinued, and the care team determined the patient no longer needed oral heart failure therapies.
“Most children with COVID-19 are either asymptomatic or have mild symptoms, but our case shows the potential for reversible myocardial injury in infants with COVID-19,” said Dr. Sharma. “Testing for COVID-19 in children presenting with signs and symptoms of heart failure is very important as we learn more about the impact of this virus.”
Dr. Sharma and coauthors have no relevant financial relationships to disclose.
SOURCE: Sharma M et al. JACC Case Rep. 2020. doi: 10.1016/j.jaccas.2020.09.031.
Reports of signs of heart failure in adults with COVID-19 have been rare – just four such cases have been published since the outbreak started in China – and now a team of pediatric cardiologists in New York have reported a case of acute but reversible myocardial injury in an infant with COVID-19.
and right upper lobe atelectasis.
The 2-month-old infant went home after more than 2 weeks in the hospital with no apparent lingering cardiac effects of the illness and not needing any oral heart failure medications, Madhu Sharma, MD, of the Children’s Hospital and Montefiore in New York and colleagues reported in JACC Case Reports. With close follow-up, the child’s left ventricle size and systolic function have remained normal and mitral regurgitation resolved. The case report didn’t mention the infant’s gender.
But before the straightforward postdischarge course emerged, the infant was in a precarious state, and Dr. Sharma and her team were challenged to diagnose the underlying causes.
The child, who was born about 7 weeks premature, first came to the hospital having turned blue after choking on food. Nonrebreather mask ventilation was initiated in the ED, and an examination detected a holosystolic murmur. A test for COVID-19 was negative, but a later test was positive, and a chest x-ray exhibited cardiomegaly and signs of fluid and inflammation in the lungs.
An electrocardiogram detected sinus tachycardia, ST-segment depression and other anomalies in cardiac function. Further investigation with a transthoracic ECG showed severely depressed left ventricle systolic function with an ejection fraction of 30%, severe mitral regurgitation, and normal right ventricular systolic function.
Treatment included remdesivir and intravenous antibiotics. Through the hospital course, the patient was extubated to noninvasive ventilation, reintubated, put on intravenous steroid (methylprednisolone) and low-molecular-weight heparin, extubated, and tested throughout for cardiac function.
By day 14, left ventricle size and function normalized, and while the mitral regurgitation remained severe, it improved later without HF therapies. Left ventricle ejection fraction had recovered to 60%, and key cardiac biomarkers had normalized. On day 16, milrinone was discontinued, and the care team determined the patient no longer needed oral heart failure therapies.
“Most children with COVID-19 are either asymptomatic or have mild symptoms, but our case shows the potential for reversible myocardial injury in infants with COVID-19,” said Dr. Sharma. “Testing for COVID-19 in children presenting with signs and symptoms of heart failure is very important as we learn more about the impact of this virus.”
Dr. Sharma and coauthors have no relevant financial relationships to disclose.
SOURCE: Sharma M et al. JACC Case Rep. 2020. doi: 10.1016/j.jaccas.2020.09.031.
Reports of signs of heart failure in adults with COVID-19 have been rare – just four such cases have been published since the outbreak started in China – and now a team of pediatric cardiologists in New York have reported a case of acute but reversible myocardial injury in an infant with COVID-19.
and right upper lobe atelectasis.
The 2-month-old infant went home after more than 2 weeks in the hospital with no apparent lingering cardiac effects of the illness and not needing any oral heart failure medications, Madhu Sharma, MD, of the Children’s Hospital and Montefiore in New York and colleagues reported in JACC Case Reports. With close follow-up, the child’s left ventricle size and systolic function have remained normal and mitral regurgitation resolved. The case report didn’t mention the infant’s gender.
But before the straightforward postdischarge course emerged, the infant was in a precarious state, and Dr. Sharma and her team were challenged to diagnose the underlying causes.
The child, who was born about 7 weeks premature, first came to the hospital having turned blue after choking on food. Nonrebreather mask ventilation was initiated in the ED, and an examination detected a holosystolic murmur. A test for COVID-19 was negative, but a later test was positive, and a chest x-ray exhibited cardiomegaly and signs of fluid and inflammation in the lungs.
An electrocardiogram detected sinus tachycardia, ST-segment depression and other anomalies in cardiac function. Further investigation with a transthoracic ECG showed severely depressed left ventricle systolic function with an ejection fraction of 30%, severe mitral regurgitation, and normal right ventricular systolic function.
Treatment included remdesivir and intravenous antibiotics. Through the hospital course, the patient was extubated to noninvasive ventilation, reintubated, put on intravenous steroid (methylprednisolone) and low-molecular-weight heparin, extubated, and tested throughout for cardiac function.
By day 14, left ventricle size and function normalized, and while the mitral regurgitation remained severe, it improved later without HF therapies. Left ventricle ejection fraction had recovered to 60%, and key cardiac biomarkers had normalized. On day 16, milrinone was discontinued, and the care team determined the patient no longer needed oral heart failure therapies.
“Most children with COVID-19 are either asymptomatic or have mild symptoms, but our case shows the potential for reversible myocardial injury in infants with COVID-19,” said Dr. Sharma. “Testing for COVID-19 in children presenting with signs and symptoms of heart failure is very important as we learn more about the impact of this virus.”
Dr. Sharma and coauthors have no relevant financial relationships to disclose.
SOURCE: Sharma M et al. JACC Case Rep. 2020. doi: 10.1016/j.jaccas.2020.09.031.
FROM JACC CASE REPORTS
Key clinical point: Children presenting with COVID-19 should be tested for heart failure.
Major finding: A 2-month-old infant with COVID-19 had acute but reversible myocardial injury.
Study details: Single case report.
Disclosures: Dr. Sharma, MD, has no relevant financial relationships to disclose.
Source: Sharma M et al. JACC Case Rep. 2020. doi: 10.1016/j.jaccas.2020.09.031.
In MDS, transplant ups survival in elderly and may be reimbursed
New results suggest that allogeneic hematopoietic cell transplantation (HCT), which is typically reserved for younger patients, may well be offered to older patients with advanced myelodysplastic syndrome (MDS).
In patients with a median age of 66 years who had received a donor transplant, the overall survival (OS) at 3 years was almost double compared with patients who did not receive a transplant – 47.9% vs. 26.6% for the “no-donor” group.
The finding comes from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study 1102 (NCT02016781) presented at the American Society of Hematology (ASH) 2020 virtual meeting.
“This study conclusively solidifies the role of transplantation in older individuals with MDS,” presenter Corey Cutler, MD, MPH, of the Dana-Farber Cancer Center, Boston, said in an interview.
Coauthor Ryotaro Nakamura, MD, of City of Hope, Duarte, Calif., said in an interview that this was the largest and first trial in the United States to determine in a prospective fashion that allogeneic stem cell transplantation offers a significant survival in older patients. “There was more than a 20% benefit in OS in this age group,” he said.
“This is an incredibly important study,” said Andrew Brunner, MD, medical oncologist at the Mass General Cancer Center in Boston, who was approached for comment. He explained that for years early transplant was recommended as important for patients who have higher-risk MDS. “This study validates this in a prospective, pseudo-randomized (donor/no donor) fashion,” he said in an interview.
“[This study] is really a seminal advance in the care of patients with MDS. Transplant should be integrated into the care algorithm, if not already, and we as a community need to build upon this study further,” Dr. Brunner added.
Several experts in addition to the authors hailed the study as practice changing.
Robert A. Brodsky, MD, ASH, director of the division of hematology at Johns Hopkins University, Baltimore, noted that in younger patients bone marrow transplant is the standard of care for aggressive MDS, but a lot of practices do not refer older patients or those with comorbidities for transplant and prefer to give these patients palliative care with hypomethylating agents for fear that the transplant process would be too toxic.
“There has been an institutional bias to do transplant in older patients, but until now there was no randomized clinical trial to show that this is the right choice. Now we have the data,” Dr Brodsky said, predicting that “this study will change the standard of care.”
Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase Cancer Center, Philadelphia, agreed. “We should congratulate all the investigators and our patients who participated in this study. Reduced intensity allogeneic stem cell transplantation improved disease control and overall survival with similar quality of life.
“I will recommend all patients with intermediate-2 or higher-risk MDS to be evaluated by the transplant team at diagnosis and eligible patients should be considered for a transplant,” Dr. Fung said in an interview.
Immediate impact on clinical practice
Lead author Dr. Cutler suggested that the study results had an immediate impact for changing clinical practice. “Individuals between the ages of 50 and 75 years with intermediate-2 or high-risk MDS who are eligible to undergo reduced-intensity transplantation had superior outcomes if they had a suitable donor for transplantation in comparison with those who did not have a donor,” he said.
Dr. Cutler further explained that many community-based hematologists do not refer their patients for transplantation. In addition, there is a lack of a uniform payer position for transplantation for MDS, he noted. Also, there is a lack of understanding of the cost-effectiveness of transplantation in comparison to nontransplant strategies, he suggested.
“Transplant is curative for MDS,” he emphasized. Most transplant recipients will eventually become transfusion-independent within weeks to months from transplant.
“We do transplants in this age group all the time,” Dr. Cutler noted. He said that academic centers will continue to offer transplants, and suggested that community oncologists encourage referral to transplant centers early in a patient’s disease course to maximize search time and provide patients all potential options for therapy.
Dr. Brunner agreed and noted that there is a need to build capacity for higher transplant volume, and in general physicians should seek ways to expand this treatment option to more patients. “At this time, allogeneic transplant still requires close collaboration with referral centers; that said, more and more we are able to work closely with colleagues in the community to share management, including earlier after the actual transplant,” he said.
He noted that one silver lining of the pandemic in 2020 has been increased use of telemedicine to collaborate. “Ongoing advances may be able to further encourage these virtual connections to enhance the entire patient care experience,” Dr. Brunner said.
Reimbursement by CMS for Medicare recipients
Despite the data showing benefit, allogeneic stem cell transplantation is not offered to older individuals with high-risk MDS and is not covered by Medicare in the United States, Dr. Cutler noted in his presentation.
“This study was spurred by the CMS [Centers for Medicare & Medicaid Services] ruling for transplantation in MDS and the story has come full circle,” Aaron T. Gerds, MD, MS, noted at a preconference press briefing. Dr. Gerds is chair of the ASH Committee on Communications and assistant professor at the Cleveland Clinic Taussig Cancer Institute, Cleveland.
Dr. Nakamura explained that in 2010 a CMS decision memo noted that the evidence of a benefit for transplantation in MDS was lacking and Medicare would not cover transplant unless patients were enrolled in a clinical study. That memo outlined criteria that a clinical trial would have to address before it could consider reimbursement for Medicare beneficiaries.
“The BMT CTN Study 1102 was one of two studies that met the criteria set by CMS,” Dr. Nakamura said, noting that the data are being prepared for CMS review.
“This study will likely be the deciding factor for CMS to begin to cover payment for transplantation for MDS,” said Dr. Cutler.
The other study, published earlier this year in JAMA Oncology, showed that outcomes for patients older than ager 65 were similar to those of patients aged 55-65.
BMT CTN 1102 study details
Dr. Cutler noted that the study was designed to address the issue of whether transplantation was beneficial to Medicare-aged individuals with high-risk MDS, and the trial had been approved by Medicare.
The multicenter study enrolled patients who were between ages 50 and 75 years and had newly diagnosed MDS of higher risk (International Prognostic Scoring System [IPSS] intermediate-2 or higher) and were candidates for reduced intensity conditioning (RIC) allogeneic HCT.
Patients were enrolled prior to a formal donor search and were initially assigned to the “no donor” group and reassigned to the donor group when a suitable donor (matched sibling or unrelated donor) was identified. Patients underwent RIC HCT according to institution protocol.
Of 384 patients, 260 received RIC HCT and 124 received hypomethylating therapy. Median follow-up was 34.2 months for the donor group and 26.9 months for the no-donor group.
The two arms were well balanced with respect to age (median 66 years), gender, disease risk [two-thirds of the patients had an intermediate-2 and one third had a high-risk MDS], and response to hypomethylating therapy. The majority of subjects in the donor arm had unrelated donors and more than one-third had a high comorbidity score, Dr. Cutler indicated.
At 3 years, absolute improvement in OS was 21.3% in favor of donor-arm subjects. Leukemia-free survival was also higher in the donor group: 35.8% vs. 20.6% for the no-donor group.
Improvement in OS for patients receiving transplants was seen across all patient subtypes, regardless of age, response to hypomethylating therapy, and IPSS score. “Treatment effects were seen in any subgroup, but particularly in subjects above age 65,” Dr. Cutler stressed.
In an as-treated analysis that excluded subjects who died, the treatment effects were even more pronounced, with an absolute improvement in OS of 31.4% (47.4% vs. 16% for the no-donor arm) and improvement in leukemia-free survival of 28.4% (39.3% vs. 10.9% for the no-donor arm).
In 25 patients in the no-donor arm who subsequently went on to receive alternate donor transplant, the 3-year OS and leukemia-free survival was 58.5%, underscoring the potential value of alternate donor transplant, Dr. Cutler noted.
Dr. Nakamura emphasized that the gains in survival benefits were not seen at the expense of quality of life, as preliminary results showed no difference in quality-of-life measures across those who received donor transplants and those who did not.
Dr. Brunner noted that physicians often highlight the toxicities of transplant as a consideration for whether to proceed, and while there are toxicities specific to transplant that should be considered, in this study it is seen that, even early on, survival is improved in those patients who move toward early transplant. “It also underscores the limitations of current nontransplant treatments for MDS – there is much room to improve,” he said.
Role for alternate donors
Dr. Cutler noted that the majority of patients in the no-donor group died without transplantation. “We need to establish the role of alternative donor transplantation in this population,” he said. Dr. Nakamura indicated that mismatched donors and haploidentical donors such as family donors and umbilical cord blood may be alternate donor sources; outcomes from published studies show similar results, he said.
However, Dr. Brunner noted that the study looked only at traditional fully matched donors, leaving open some questions about alternative donor options such as haploidentical donors and umbilical cord blood donation.
“Our experience in other areas of transplant would suggest that these donor sources may be as good as traditional fully matched options, when using newer conditioning and prophylaxis regimens,” Dr. Brunner said.
Dr. Cutler added, “With the increased acceptance of alternate transplant modalities, we need to determine the outcomes associated with these in prospective trials.”
“I think a significant consideration here as well is health equity,” Dr. Brunner said. “Donor options vary according to race and ethnicity and we need to be proactive as a community to ensure that all MDS patients have access to a potentially curative option early in their diagnosis.”
Dr. Cutler reports consultancy for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte. Dr. Nakamura reports relationships with Magenta Therapeutics, Kyowa-Kirin, Alexion, Merck, NapaJen Pharma, Kadmon Corporation, Celgene, and Viracor. Dr. Fung has disclosed no relevant financial relationships. Dr. Brodsky reports receiving funding from and being on the board/advisory committee for Achillion Pharmaceuticals, consults with Alexion Pharmaceuticals, and receives honoraria from UpToDate. Dr. Brunner reports relationships with Biogen, Acceleron Pharma Inc, Celgene/BMS, Forty Seven Inc, Jazz Pharma, Novartis, Takeda, Xcenda, GSK, Janssen, and AstraZeneca.
A version of this article originally appeared on Medscape.com.
New results suggest that allogeneic hematopoietic cell transplantation (HCT), which is typically reserved for younger patients, may well be offered to older patients with advanced myelodysplastic syndrome (MDS).
In patients with a median age of 66 years who had received a donor transplant, the overall survival (OS) at 3 years was almost double compared with patients who did not receive a transplant – 47.9% vs. 26.6% for the “no-donor” group.
The finding comes from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study 1102 (NCT02016781) presented at the American Society of Hematology (ASH) 2020 virtual meeting.
“This study conclusively solidifies the role of transplantation in older individuals with MDS,” presenter Corey Cutler, MD, MPH, of the Dana-Farber Cancer Center, Boston, said in an interview.
Coauthor Ryotaro Nakamura, MD, of City of Hope, Duarte, Calif., said in an interview that this was the largest and first trial in the United States to determine in a prospective fashion that allogeneic stem cell transplantation offers a significant survival in older patients. “There was more than a 20% benefit in OS in this age group,” he said.
“This is an incredibly important study,” said Andrew Brunner, MD, medical oncologist at the Mass General Cancer Center in Boston, who was approached for comment. He explained that for years early transplant was recommended as important for patients who have higher-risk MDS. “This study validates this in a prospective, pseudo-randomized (donor/no donor) fashion,” he said in an interview.
“[This study] is really a seminal advance in the care of patients with MDS. Transplant should be integrated into the care algorithm, if not already, and we as a community need to build upon this study further,” Dr. Brunner added.
Several experts in addition to the authors hailed the study as practice changing.
Robert A. Brodsky, MD, ASH, director of the division of hematology at Johns Hopkins University, Baltimore, noted that in younger patients bone marrow transplant is the standard of care for aggressive MDS, but a lot of practices do not refer older patients or those with comorbidities for transplant and prefer to give these patients palliative care with hypomethylating agents for fear that the transplant process would be too toxic.
“There has been an institutional bias to do transplant in older patients, but until now there was no randomized clinical trial to show that this is the right choice. Now we have the data,” Dr Brodsky said, predicting that “this study will change the standard of care.”
Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase Cancer Center, Philadelphia, agreed. “We should congratulate all the investigators and our patients who participated in this study. Reduced intensity allogeneic stem cell transplantation improved disease control and overall survival with similar quality of life.
“I will recommend all patients with intermediate-2 or higher-risk MDS to be evaluated by the transplant team at diagnosis and eligible patients should be considered for a transplant,” Dr. Fung said in an interview.
Immediate impact on clinical practice
Lead author Dr. Cutler suggested that the study results had an immediate impact for changing clinical practice. “Individuals between the ages of 50 and 75 years with intermediate-2 or high-risk MDS who are eligible to undergo reduced-intensity transplantation had superior outcomes if they had a suitable donor for transplantation in comparison with those who did not have a donor,” he said.
Dr. Cutler further explained that many community-based hematologists do not refer their patients for transplantation. In addition, there is a lack of a uniform payer position for transplantation for MDS, he noted. Also, there is a lack of understanding of the cost-effectiveness of transplantation in comparison to nontransplant strategies, he suggested.
“Transplant is curative for MDS,” he emphasized. Most transplant recipients will eventually become transfusion-independent within weeks to months from transplant.
“We do transplants in this age group all the time,” Dr. Cutler noted. He said that academic centers will continue to offer transplants, and suggested that community oncologists encourage referral to transplant centers early in a patient’s disease course to maximize search time and provide patients all potential options for therapy.
Dr. Brunner agreed and noted that there is a need to build capacity for higher transplant volume, and in general physicians should seek ways to expand this treatment option to more patients. “At this time, allogeneic transplant still requires close collaboration with referral centers; that said, more and more we are able to work closely with colleagues in the community to share management, including earlier after the actual transplant,” he said.
He noted that one silver lining of the pandemic in 2020 has been increased use of telemedicine to collaborate. “Ongoing advances may be able to further encourage these virtual connections to enhance the entire patient care experience,” Dr. Brunner said.
Reimbursement by CMS for Medicare recipients
Despite the data showing benefit, allogeneic stem cell transplantation is not offered to older individuals with high-risk MDS and is not covered by Medicare in the United States, Dr. Cutler noted in his presentation.
“This study was spurred by the CMS [Centers for Medicare & Medicaid Services] ruling for transplantation in MDS and the story has come full circle,” Aaron T. Gerds, MD, MS, noted at a preconference press briefing. Dr. Gerds is chair of the ASH Committee on Communications and assistant professor at the Cleveland Clinic Taussig Cancer Institute, Cleveland.
Dr. Nakamura explained that in 2010 a CMS decision memo noted that the evidence of a benefit for transplantation in MDS was lacking and Medicare would not cover transplant unless patients were enrolled in a clinical study. That memo outlined criteria that a clinical trial would have to address before it could consider reimbursement for Medicare beneficiaries.
“The BMT CTN Study 1102 was one of two studies that met the criteria set by CMS,” Dr. Nakamura said, noting that the data are being prepared for CMS review.
“This study will likely be the deciding factor for CMS to begin to cover payment for transplantation for MDS,” said Dr. Cutler.
The other study, published earlier this year in JAMA Oncology, showed that outcomes for patients older than ager 65 were similar to those of patients aged 55-65.
BMT CTN 1102 study details
Dr. Cutler noted that the study was designed to address the issue of whether transplantation was beneficial to Medicare-aged individuals with high-risk MDS, and the trial had been approved by Medicare.
The multicenter study enrolled patients who were between ages 50 and 75 years and had newly diagnosed MDS of higher risk (International Prognostic Scoring System [IPSS] intermediate-2 or higher) and were candidates for reduced intensity conditioning (RIC) allogeneic HCT.
Patients were enrolled prior to a formal donor search and were initially assigned to the “no donor” group and reassigned to the donor group when a suitable donor (matched sibling or unrelated donor) was identified. Patients underwent RIC HCT according to institution protocol.
Of 384 patients, 260 received RIC HCT and 124 received hypomethylating therapy. Median follow-up was 34.2 months for the donor group and 26.9 months for the no-donor group.
The two arms were well balanced with respect to age (median 66 years), gender, disease risk [two-thirds of the patients had an intermediate-2 and one third had a high-risk MDS], and response to hypomethylating therapy. The majority of subjects in the donor arm had unrelated donors and more than one-third had a high comorbidity score, Dr. Cutler indicated.
At 3 years, absolute improvement in OS was 21.3% in favor of donor-arm subjects. Leukemia-free survival was also higher in the donor group: 35.8% vs. 20.6% for the no-donor group.
Improvement in OS for patients receiving transplants was seen across all patient subtypes, regardless of age, response to hypomethylating therapy, and IPSS score. “Treatment effects were seen in any subgroup, but particularly in subjects above age 65,” Dr. Cutler stressed.
In an as-treated analysis that excluded subjects who died, the treatment effects were even more pronounced, with an absolute improvement in OS of 31.4% (47.4% vs. 16% for the no-donor arm) and improvement in leukemia-free survival of 28.4% (39.3% vs. 10.9% for the no-donor arm).
In 25 patients in the no-donor arm who subsequently went on to receive alternate donor transplant, the 3-year OS and leukemia-free survival was 58.5%, underscoring the potential value of alternate donor transplant, Dr. Cutler noted.
Dr. Nakamura emphasized that the gains in survival benefits were not seen at the expense of quality of life, as preliminary results showed no difference in quality-of-life measures across those who received donor transplants and those who did not.
Dr. Brunner noted that physicians often highlight the toxicities of transplant as a consideration for whether to proceed, and while there are toxicities specific to transplant that should be considered, in this study it is seen that, even early on, survival is improved in those patients who move toward early transplant. “It also underscores the limitations of current nontransplant treatments for MDS – there is much room to improve,” he said.
Role for alternate donors
Dr. Cutler noted that the majority of patients in the no-donor group died without transplantation. “We need to establish the role of alternative donor transplantation in this population,” he said. Dr. Nakamura indicated that mismatched donors and haploidentical donors such as family donors and umbilical cord blood may be alternate donor sources; outcomes from published studies show similar results, he said.
However, Dr. Brunner noted that the study looked only at traditional fully matched donors, leaving open some questions about alternative donor options such as haploidentical donors and umbilical cord blood donation.
“Our experience in other areas of transplant would suggest that these donor sources may be as good as traditional fully matched options, when using newer conditioning and prophylaxis regimens,” Dr. Brunner said.
Dr. Cutler added, “With the increased acceptance of alternate transplant modalities, we need to determine the outcomes associated with these in prospective trials.”
“I think a significant consideration here as well is health equity,” Dr. Brunner said. “Donor options vary according to race and ethnicity and we need to be proactive as a community to ensure that all MDS patients have access to a potentially curative option early in their diagnosis.”
Dr. Cutler reports consultancy for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte. Dr. Nakamura reports relationships with Magenta Therapeutics, Kyowa-Kirin, Alexion, Merck, NapaJen Pharma, Kadmon Corporation, Celgene, and Viracor. Dr. Fung has disclosed no relevant financial relationships. Dr. Brodsky reports receiving funding from and being on the board/advisory committee for Achillion Pharmaceuticals, consults with Alexion Pharmaceuticals, and receives honoraria from UpToDate. Dr. Brunner reports relationships with Biogen, Acceleron Pharma Inc, Celgene/BMS, Forty Seven Inc, Jazz Pharma, Novartis, Takeda, Xcenda, GSK, Janssen, and AstraZeneca.
A version of this article originally appeared on Medscape.com.
New results suggest that allogeneic hematopoietic cell transplantation (HCT), which is typically reserved for younger patients, may well be offered to older patients with advanced myelodysplastic syndrome (MDS).
In patients with a median age of 66 years who had received a donor transplant, the overall survival (OS) at 3 years was almost double compared with patients who did not receive a transplant – 47.9% vs. 26.6% for the “no-donor” group.
The finding comes from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study 1102 (NCT02016781) presented at the American Society of Hematology (ASH) 2020 virtual meeting.
“This study conclusively solidifies the role of transplantation in older individuals with MDS,” presenter Corey Cutler, MD, MPH, of the Dana-Farber Cancer Center, Boston, said in an interview.
Coauthor Ryotaro Nakamura, MD, of City of Hope, Duarte, Calif., said in an interview that this was the largest and first trial in the United States to determine in a prospective fashion that allogeneic stem cell transplantation offers a significant survival in older patients. “There was more than a 20% benefit in OS in this age group,” he said.
“This is an incredibly important study,” said Andrew Brunner, MD, medical oncologist at the Mass General Cancer Center in Boston, who was approached for comment. He explained that for years early transplant was recommended as important for patients who have higher-risk MDS. “This study validates this in a prospective, pseudo-randomized (donor/no donor) fashion,” he said in an interview.
“[This study] is really a seminal advance in the care of patients with MDS. Transplant should be integrated into the care algorithm, if not already, and we as a community need to build upon this study further,” Dr. Brunner added.
Several experts in addition to the authors hailed the study as practice changing.
Robert A. Brodsky, MD, ASH, director of the division of hematology at Johns Hopkins University, Baltimore, noted that in younger patients bone marrow transplant is the standard of care for aggressive MDS, but a lot of practices do not refer older patients or those with comorbidities for transplant and prefer to give these patients palliative care with hypomethylating agents for fear that the transplant process would be too toxic.
“There has been an institutional bias to do transplant in older patients, but until now there was no randomized clinical trial to show that this is the right choice. Now we have the data,” Dr Brodsky said, predicting that “this study will change the standard of care.”
Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase Cancer Center, Philadelphia, agreed. “We should congratulate all the investigators and our patients who participated in this study. Reduced intensity allogeneic stem cell transplantation improved disease control and overall survival with similar quality of life.
“I will recommend all patients with intermediate-2 or higher-risk MDS to be evaluated by the transplant team at diagnosis and eligible patients should be considered for a transplant,” Dr. Fung said in an interview.
Immediate impact on clinical practice
Lead author Dr. Cutler suggested that the study results had an immediate impact for changing clinical practice. “Individuals between the ages of 50 and 75 years with intermediate-2 or high-risk MDS who are eligible to undergo reduced-intensity transplantation had superior outcomes if they had a suitable donor for transplantation in comparison with those who did not have a donor,” he said.
Dr. Cutler further explained that many community-based hematologists do not refer their patients for transplantation. In addition, there is a lack of a uniform payer position for transplantation for MDS, he noted. Also, there is a lack of understanding of the cost-effectiveness of transplantation in comparison to nontransplant strategies, he suggested.
“Transplant is curative for MDS,” he emphasized. Most transplant recipients will eventually become transfusion-independent within weeks to months from transplant.
“We do transplants in this age group all the time,” Dr. Cutler noted. He said that academic centers will continue to offer transplants, and suggested that community oncologists encourage referral to transplant centers early in a patient’s disease course to maximize search time and provide patients all potential options for therapy.
Dr. Brunner agreed and noted that there is a need to build capacity for higher transplant volume, and in general physicians should seek ways to expand this treatment option to more patients. “At this time, allogeneic transplant still requires close collaboration with referral centers; that said, more and more we are able to work closely with colleagues in the community to share management, including earlier after the actual transplant,” he said.
He noted that one silver lining of the pandemic in 2020 has been increased use of telemedicine to collaborate. “Ongoing advances may be able to further encourage these virtual connections to enhance the entire patient care experience,” Dr. Brunner said.
Reimbursement by CMS for Medicare recipients
Despite the data showing benefit, allogeneic stem cell transplantation is not offered to older individuals with high-risk MDS and is not covered by Medicare in the United States, Dr. Cutler noted in his presentation.
“This study was spurred by the CMS [Centers for Medicare & Medicaid Services] ruling for transplantation in MDS and the story has come full circle,” Aaron T. Gerds, MD, MS, noted at a preconference press briefing. Dr. Gerds is chair of the ASH Committee on Communications and assistant professor at the Cleveland Clinic Taussig Cancer Institute, Cleveland.
Dr. Nakamura explained that in 2010 a CMS decision memo noted that the evidence of a benefit for transplantation in MDS was lacking and Medicare would not cover transplant unless patients were enrolled in a clinical study. That memo outlined criteria that a clinical trial would have to address before it could consider reimbursement for Medicare beneficiaries.
“The BMT CTN Study 1102 was one of two studies that met the criteria set by CMS,” Dr. Nakamura said, noting that the data are being prepared for CMS review.
“This study will likely be the deciding factor for CMS to begin to cover payment for transplantation for MDS,” said Dr. Cutler.
The other study, published earlier this year in JAMA Oncology, showed that outcomes for patients older than ager 65 were similar to those of patients aged 55-65.
BMT CTN 1102 study details
Dr. Cutler noted that the study was designed to address the issue of whether transplantation was beneficial to Medicare-aged individuals with high-risk MDS, and the trial had been approved by Medicare.
The multicenter study enrolled patients who were between ages 50 and 75 years and had newly diagnosed MDS of higher risk (International Prognostic Scoring System [IPSS] intermediate-2 or higher) and were candidates for reduced intensity conditioning (RIC) allogeneic HCT.
Patients were enrolled prior to a formal donor search and were initially assigned to the “no donor” group and reassigned to the donor group when a suitable donor (matched sibling or unrelated donor) was identified. Patients underwent RIC HCT according to institution protocol.
Of 384 patients, 260 received RIC HCT and 124 received hypomethylating therapy. Median follow-up was 34.2 months for the donor group and 26.9 months for the no-donor group.
The two arms were well balanced with respect to age (median 66 years), gender, disease risk [two-thirds of the patients had an intermediate-2 and one third had a high-risk MDS], and response to hypomethylating therapy. The majority of subjects in the donor arm had unrelated donors and more than one-third had a high comorbidity score, Dr. Cutler indicated.
At 3 years, absolute improvement in OS was 21.3% in favor of donor-arm subjects. Leukemia-free survival was also higher in the donor group: 35.8% vs. 20.6% for the no-donor group.
Improvement in OS for patients receiving transplants was seen across all patient subtypes, regardless of age, response to hypomethylating therapy, and IPSS score. “Treatment effects were seen in any subgroup, but particularly in subjects above age 65,” Dr. Cutler stressed.
In an as-treated analysis that excluded subjects who died, the treatment effects were even more pronounced, with an absolute improvement in OS of 31.4% (47.4% vs. 16% for the no-donor arm) and improvement in leukemia-free survival of 28.4% (39.3% vs. 10.9% for the no-donor arm).
In 25 patients in the no-donor arm who subsequently went on to receive alternate donor transplant, the 3-year OS and leukemia-free survival was 58.5%, underscoring the potential value of alternate donor transplant, Dr. Cutler noted.
Dr. Nakamura emphasized that the gains in survival benefits were not seen at the expense of quality of life, as preliminary results showed no difference in quality-of-life measures across those who received donor transplants and those who did not.
Dr. Brunner noted that physicians often highlight the toxicities of transplant as a consideration for whether to proceed, and while there are toxicities specific to transplant that should be considered, in this study it is seen that, even early on, survival is improved in those patients who move toward early transplant. “It also underscores the limitations of current nontransplant treatments for MDS – there is much room to improve,” he said.
Role for alternate donors
Dr. Cutler noted that the majority of patients in the no-donor group died without transplantation. “We need to establish the role of alternative donor transplantation in this population,” he said. Dr. Nakamura indicated that mismatched donors and haploidentical donors such as family donors and umbilical cord blood may be alternate donor sources; outcomes from published studies show similar results, he said.
However, Dr. Brunner noted that the study looked only at traditional fully matched donors, leaving open some questions about alternative donor options such as haploidentical donors and umbilical cord blood donation.
“Our experience in other areas of transplant would suggest that these donor sources may be as good as traditional fully matched options, when using newer conditioning and prophylaxis regimens,” Dr. Brunner said.
Dr. Cutler added, “With the increased acceptance of alternate transplant modalities, we need to determine the outcomes associated with these in prospective trials.”
“I think a significant consideration here as well is health equity,” Dr. Brunner said. “Donor options vary according to race and ethnicity and we need to be proactive as a community to ensure that all MDS patients have access to a potentially curative option early in their diagnosis.”
Dr. Cutler reports consultancy for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte. Dr. Nakamura reports relationships with Magenta Therapeutics, Kyowa-Kirin, Alexion, Merck, NapaJen Pharma, Kadmon Corporation, Celgene, and Viracor. Dr. Fung has disclosed no relevant financial relationships. Dr. Brodsky reports receiving funding from and being on the board/advisory committee for Achillion Pharmaceuticals, consults with Alexion Pharmaceuticals, and receives honoraria from UpToDate. Dr. Brunner reports relationships with Biogen, Acceleron Pharma Inc, Celgene/BMS, Forty Seven Inc, Jazz Pharma, Novartis, Takeda, Xcenda, GSK, Janssen, and AstraZeneca.
A version of this article originally appeared on Medscape.com.
Cancer rates on the rise in adolescents and young adults
Rates of cancer increased by 30% from 1973 to 2015 in adolescents and young adults (AYAs) aged 15–39 years in the United States, according to a review of almost a half million cases in the National Institutes of Health’s Surveillance, Epidemiology, and End Results database.
There was an annual increase of 0.537 new cases per 100,000 people, from 57.2 cases per 100,000 in 1973 to 74.2 in 2015.
Kidney carcinoma led with the highest rate increase. There were also marked increases in thyroid and colorectal carcinoma, germ cell and trophoblastic neoplasms, and melanoma, among others.
The report was published online December 1 in JAMA Network Open.
“Clinicians should be on the lookout for these cancers in their adolescent and young adult patients,” said senior investigator Nicholas Zaorsky, MD, an assistant professor of radiation oncology and public health sciences at the Penn State Cancer Institute, Hershey, Pennsylvania.
“Now that there is a better understanding of the types of cancer that are prevalent and rising in this age group, prevention, screening, diagnosis and treatment protocols specifically targeted to this population should be developed,” he said in a press release.
The reasons for the increases are unclear, but environmental and dietary factors, increasing obesity, and changing screening practices are likely in play, the authors comment. In addition, “cancer screening and overdiagnosis are thought to account for much of the increasing rates of thyroid and kidney carcinoma, among others,” they add.
The American Cancer Society (ACS) recently found similar increases in thyroid, kidney, and colorectal cancer among AYAs, as well as an increase in uterine cancer.
It’s important to note, however, that “this phenomenon is largely driven by trends for thyroid cancer, which is thought to be a result of overdiagnosis,” said ACS surveillance researcher Kimberly Miller, MPH, when asked to comment on the new study.
“As such, it is extremely important to also consider trends in cancer mortality rates among this age group, which are declining overall but are increasing for colorectal and uterine cancers. The fact that both incidence and mortality rates are increasing for these two cancers suggests a true increase in disease burden and certainly requires further attention and research,” she said.
Historically, management of cancer in AYAs has fallen somewhere between pediatric and adult oncology, neither of which capture the distinct biological, social, and economic needs of AYAs. Research has also focused on childhood and adult cancers, leaving cancer in AYAs inadequately studied.
The new findings are “valuable to guide more targeted research and interventions specifically to AYAs,” Zaorsky and colleagues say in their report.
Among female patients ― 59.1% of the study population ― incidence increased for 15 cancers, including kidney carcinoma (annual percent change [APC], 3.632), thyroid carcinoma (APC, 3.456), and myeloma, mast cell, and miscellaneous lymphoreticular neoplasms not otherwise specified (APC, 2.805). Rates of five cancers declined, led by astrocytoma not otherwise specified (APC, –3.369) and carcinoma of the gonads (APC, –1.743).
Among male patients, incidence increased for 14 cancers, including kidney carcinoma (APC, 3.572), unspecified soft tissue sarcoma (APC 2.543), and thyroid carcinoma (APC, 2.273). Incidence fell for seven, led by astrocytoma not otherwise specified (APC, –3.759) and carcinoma of the trachea, bronchus, and lung (APC, –2.635).
Increased testicular cancer rates (APC, 1.246) could be related to greater prenatal exposure to estrogen and progesterone or through dairy consumption; increasing survival of premature infants; and greater exposure to cannabis, among other possibilities, the investigators say.
Increases in colorectal cancer might be related to fewer vegetables and more fat and processed meat in the diet; lack of exercise; and increasing obesity. Human papillomavirus infection has also been implicated.
Higher rates of melanoma could be related to tanning bed use.
Declines in some cancers could be related to greater use of oral contraceptives; laws reducing exposure to benzene and other chemicals; and fewer people smoking.
Although kidney carcinoma has increased at the greatest rate, it’s uncommon. Colorectal and thyroid carcinoma, melanoma, non-Hodgkin lymphoma, and germ cell and trophoblastic neoplasms of the gonads contribute more to the overall increase in cancers among AYAs, the investigators note.
Almost 80% of the patients were White; 10.3% were Black.
The study was funded by the National Center for Advancing Translational Sciences. The investigators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Rates of cancer increased by 30% from 1973 to 2015 in adolescents and young adults (AYAs) aged 15–39 years in the United States, according to a review of almost a half million cases in the National Institutes of Health’s Surveillance, Epidemiology, and End Results database.
There was an annual increase of 0.537 new cases per 100,000 people, from 57.2 cases per 100,000 in 1973 to 74.2 in 2015.
Kidney carcinoma led with the highest rate increase. There were also marked increases in thyroid and colorectal carcinoma, germ cell and trophoblastic neoplasms, and melanoma, among others.
The report was published online December 1 in JAMA Network Open.
“Clinicians should be on the lookout for these cancers in their adolescent and young adult patients,” said senior investigator Nicholas Zaorsky, MD, an assistant professor of radiation oncology and public health sciences at the Penn State Cancer Institute, Hershey, Pennsylvania.
“Now that there is a better understanding of the types of cancer that are prevalent and rising in this age group, prevention, screening, diagnosis and treatment protocols specifically targeted to this population should be developed,” he said in a press release.
The reasons for the increases are unclear, but environmental and dietary factors, increasing obesity, and changing screening practices are likely in play, the authors comment. In addition, “cancer screening and overdiagnosis are thought to account for much of the increasing rates of thyroid and kidney carcinoma, among others,” they add.
The American Cancer Society (ACS) recently found similar increases in thyroid, kidney, and colorectal cancer among AYAs, as well as an increase in uterine cancer.
It’s important to note, however, that “this phenomenon is largely driven by trends for thyroid cancer, which is thought to be a result of overdiagnosis,” said ACS surveillance researcher Kimberly Miller, MPH, when asked to comment on the new study.
“As such, it is extremely important to also consider trends in cancer mortality rates among this age group, which are declining overall but are increasing for colorectal and uterine cancers. The fact that both incidence and mortality rates are increasing for these two cancers suggests a true increase in disease burden and certainly requires further attention and research,” she said.
Historically, management of cancer in AYAs has fallen somewhere between pediatric and adult oncology, neither of which capture the distinct biological, social, and economic needs of AYAs. Research has also focused on childhood and adult cancers, leaving cancer in AYAs inadequately studied.
The new findings are “valuable to guide more targeted research and interventions specifically to AYAs,” Zaorsky and colleagues say in their report.
Among female patients ― 59.1% of the study population ― incidence increased for 15 cancers, including kidney carcinoma (annual percent change [APC], 3.632), thyroid carcinoma (APC, 3.456), and myeloma, mast cell, and miscellaneous lymphoreticular neoplasms not otherwise specified (APC, 2.805). Rates of five cancers declined, led by astrocytoma not otherwise specified (APC, –3.369) and carcinoma of the gonads (APC, –1.743).
Among male patients, incidence increased for 14 cancers, including kidney carcinoma (APC, 3.572), unspecified soft tissue sarcoma (APC 2.543), and thyroid carcinoma (APC, 2.273). Incidence fell for seven, led by astrocytoma not otherwise specified (APC, –3.759) and carcinoma of the trachea, bronchus, and lung (APC, –2.635).
Increased testicular cancer rates (APC, 1.246) could be related to greater prenatal exposure to estrogen and progesterone or through dairy consumption; increasing survival of premature infants; and greater exposure to cannabis, among other possibilities, the investigators say.
Increases in colorectal cancer might be related to fewer vegetables and more fat and processed meat in the diet; lack of exercise; and increasing obesity. Human papillomavirus infection has also been implicated.
Higher rates of melanoma could be related to tanning bed use.
Declines in some cancers could be related to greater use of oral contraceptives; laws reducing exposure to benzene and other chemicals; and fewer people smoking.
Although kidney carcinoma has increased at the greatest rate, it’s uncommon. Colorectal and thyroid carcinoma, melanoma, non-Hodgkin lymphoma, and germ cell and trophoblastic neoplasms of the gonads contribute more to the overall increase in cancers among AYAs, the investigators note.
Almost 80% of the patients were White; 10.3% were Black.
The study was funded by the National Center for Advancing Translational Sciences. The investigators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Rates of cancer increased by 30% from 1973 to 2015 in adolescents and young adults (AYAs) aged 15–39 years in the United States, according to a review of almost a half million cases in the National Institutes of Health’s Surveillance, Epidemiology, and End Results database.
There was an annual increase of 0.537 new cases per 100,000 people, from 57.2 cases per 100,000 in 1973 to 74.2 in 2015.
Kidney carcinoma led with the highest rate increase. There were also marked increases in thyroid and colorectal carcinoma, germ cell and trophoblastic neoplasms, and melanoma, among others.
The report was published online December 1 in JAMA Network Open.
“Clinicians should be on the lookout for these cancers in their adolescent and young adult patients,” said senior investigator Nicholas Zaorsky, MD, an assistant professor of radiation oncology and public health sciences at the Penn State Cancer Institute, Hershey, Pennsylvania.
“Now that there is a better understanding of the types of cancer that are prevalent and rising in this age group, prevention, screening, diagnosis and treatment protocols specifically targeted to this population should be developed,” he said in a press release.
The reasons for the increases are unclear, but environmental and dietary factors, increasing obesity, and changing screening practices are likely in play, the authors comment. In addition, “cancer screening and overdiagnosis are thought to account for much of the increasing rates of thyroid and kidney carcinoma, among others,” they add.
The American Cancer Society (ACS) recently found similar increases in thyroid, kidney, and colorectal cancer among AYAs, as well as an increase in uterine cancer.
It’s important to note, however, that “this phenomenon is largely driven by trends for thyroid cancer, which is thought to be a result of overdiagnosis,” said ACS surveillance researcher Kimberly Miller, MPH, when asked to comment on the new study.
“As such, it is extremely important to also consider trends in cancer mortality rates among this age group, which are declining overall but are increasing for colorectal and uterine cancers. The fact that both incidence and mortality rates are increasing for these two cancers suggests a true increase in disease burden and certainly requires further attention and research,” she said.
Historically, management of cancer in AYAs has fallen somewhere between pediatric and adult oncology, neither of which capture the distinct biological, social, and economic needs of AYAs. Research has also focused on childhood and adult cancers, leaving cancer in AYAs inadequately studied.
The new findings are “valuable to guide more targeted research and interventions specifically to AYAs,” Zaorsky and colleagues say in their report.
Among female patients ― 59.1% of the study population ― incidence increased for 15 cancers, including kidney carcinoma (annual percent change [APC], 3.632), thyroid carcinoma (APC, 3.456), and myeloma, mast cell, and miscellaneous lymphoreticular neoplasms not otherwise specified (APC, 2.805). Rates of five cancers declined, led by astrocytoma not otherwise specified (APC, –3.369) and carcinoma of the gonads (APC, –1.743).
Among male patients, incidence increased for 14 cancers, including kidney carcinoma (APC, 3.572), unspecified soft tissue sarcoma (APC 2.543), and thyroid carcinoma (APC, 2.273). Incidence fell for seven, led by astrocytoma not otherwise specified (APC, –3.759) and carcinoma of the trachea, bronchus, and lung (APC, –2.635).
Increased testicular cancer rates (APC, 1.246) could be related to greater prenatal exposure to estrogen and progesterone or through dairy consumption; increasing survival of premature infants; and greater exposure to cannabis, among other possibilities, the investigators say.
Increases in colorectal cancer might be related to fewer vegetables and more fat and processed meat in the diet; lack of exercise; and increasing obesity. Human papillomavirus infection has also been implicated.
Higher rates of melanoma could be related to tanning bed use.
Declines in some cancers could be related to greater use of oral contraceptives; laws reducing exposure to benzene and other chemicals; and fewer people smoking.
Although kidney carcinoma has increased at the greatest rate, it’s uncommon. Colorectal and thyroid carcinoma, melanoma, non-Hodgkin lymphoma, and germ cell and trophoblastic neoplasms of the gonads contribute more to the overall increase in cancers among AYAs, the investigators note.
Almost 80% of the patients were White; 10.3% were Black.
The study was funded by the National Center for Advancing Translational Sciences. The investigators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
VTE prophylaxis is feasible, effective in some high-risk cancer patients
Primary thromboprophylaxis is feasible and worth considering for high-risk ambulatory patients with cancer who are initiating systemic chemotherapy, according to Marc Carrier, MD.
Risk scores can identify patients at high risk for venous thromboembolism (VTE), and treatments that are effective and associated with low bleeding risk are available, Dr. Carrier explained at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
However, caution is advised in patients with certain types of cancer, including some gastrointestinal and genitourinary cancers, because of the possibility of increased major and clinically relevant nonmajor bleeding risk, he said.
VTE and cancer
VTE is relatively rare in the general population, occurring in about 1 or 2 per 1,000 people annually. The risk increases 4.1-fold in patients with cancer, and 6.5-fold in patients with cancer receiving chemotherapy.
“So just putting these numbers together, we’re no longer talking about 1 in 1,000, but 1 in 200, so [this is] something that is very common among cancer patients,” said Dr. Carrier, a professor at the University of Ottawa and chief of the division of hematology at The Ottawa Hospital.
The mortality rate associated with cancer-associated thrombosis is about 9%, comparable to that associated with infection in the cancer outpatient setting, which underscores the importance of educating patients about the signs and symptoms of VTE so they can seek medical treatment quickly if necessary, he added.
It may also be useful to discuss prophylaxis or other ways to prevent venous thromboembolic complications with certain patients, he said, noting that in an observational cohort study of nearly 600 patients at the University of Ottawa, 25% of those initiating chemotherapy were identified as intermediate or high risk using the validated Khorana risk score, and thus would likely benefit from thromboprophylaxis.
Risk assessment
The Khorana risk score assesses VTE risk based on cancer site, blood counts, and body mass index. It is simple to use and has been validated in more than 20,000 people in multiple countries, Dr. Carrier said.
In a well-known validation study, Ay et al. showed a VTE complication rate of 10% in patients with a Khorana risk score of 2 or higher who were followed up to 6 months.
“This is huge,” Dr. Carrier stressed. “This is much higher than what we tolerate for all sorts of different populations for which we would recommend anticoagulation or thromboprophylaxis.”
The question is whether the risk score can be helpful in a real-world clinic setting, he said, adding: “I’d like to think the answer to that is yes.”
In the University of Ottawa cohort study, 11% of high-risk patients experienced a VTE complication, compared with 4% of those with lower risk, suggesting that the validation data for the Khorana risk score is not only accurate, it is “actually applicable in real-world practice, and you can use it in your own center,” he said.
Further, recent studies have demonstrated that treatment based on Khorana risk score assessment reduces VTE complications.
Prophylaxis options
Low-molecular-weight heparin (LMWH) has been shown in several studies to be associated with a significant relative VTE risk reduction in patients with cancer initiating chemotherapy – with only a slight, nonsignificant increase in the risk of major bleeding.
However, the absolute benefit was small, and LMWH is “parenteral, relatively costly, and, based on that, although we showed relatively good risk-benefit ratio, it never really got translated to clinical practice,” Dr. Carrier said.
In fact, a 2015 American Society of Clinical Oncology guidelines update recommended against routine thromboprophylaxis in this setting, but stated that it could be considered in select high-risk patients identified using a validated risk-assessment tool.
The guidelines noted that “individual risk factors such as biomarkers and cancer site don’t reliably identify high-risk patients.”
More recent data provide additional support for risk assessment and treatment based on Khorana risk score of 2 or higher.
The AVERT trial, for which Dr. Carrier was the first author, showed that the direct-acting oral anticoagulant (DOAC) apixaban reduced VTE incidence, compared with placebo, in patients with Khorana score of 2 or higher (4.2% vs. 10.2%; hazard ratio, 0.41 overall, and 1.0 vs. 7.3; HR, 0.14 on treatment), and the CASSINI trial showed that another DOAC, rivaroxaban, reduced VTE incidence, compared with placebo, in those with Khorana score of 2 or higher (5.9 vs. 6.7; HR, 0.6 overall, and 2.6 vs. 6.4; HR, 0.40 on treatment). The differences in the on-treatment populations were statistically significant.
The two trials, which included a variety of tumor types, showed similar rates of major bleeding, with an absolute difference of about 1% between treatment and placebo, which was not statistically significant in the on-treatment analyses (HR, 1.89 in AVERT and HR, 1.96 in CASSINI).
A systematic review of these trials showed an overall significant decrease in VTE complication risk with treatment in high-risk patients, and a nonstatistically significant major bleeding risk increase.
Based on these findings, ASCO guidelines were updated in 2020 to state that “routine thromboprophylaxis should not be offered to all patients with cancer. ... However, high-risk outpatients with cancer may be offered thromboprophylaxis with apixaban, rivaroxaban or LMWH, providing there are no significant risk factors for bleeding or drug-drug interactions, and after having a full discussion with patients ... to make sure they understand the risk-benefit ratio and the rationale for that particular recommendation,” he said.
Real-world implementation
Implementing this approach in the clinic setting requires a practical model, such as the Venous Thromboembolism Prevention in the Ambulatory Cancer Clinic (VTEPACC) program, a prospective quality improvement research initiative developed in collaboration with the Jeffords Institute for Quality at the University of Vermont Medical Center and described in a recent report, Dr. Carrier said.
The “Vermont model” is “really a comprehensive model that includes identifying patients with the electronic medical records, gathering the formal education and insight from other health care providers like pharmacists and nurses in order to really come up with personalized care for your patients,” he explained.
In 918 outpatients with cancer who were included in the program, VTE awareness increased from less than 5% before VTEPACC to nearly 82% during the implementation phase and 94.7% after 2 years, with nearly 94% of high-risk patients receiving VTE prophylaxis at that time.
“So we can certainly do that in our own center.” he said. “It’s a matter of coming up with the model and making sure that the patients are seen at the right time.”
Given the high frequency of VTE in patients with cancer initiating chemotherapy, the usefulness of risk scores such as the Khorana risk score for identifying those at high risk, and the availability of safe and effective interventions for reducing risk, “we should probably use the data and incorporate them into clinical practice by implementation of programs for primary prevention,” he said.
A word of caution
Caution is warranted, however, when it comes to using DOACs in patients with higher-risk or potentially higher-risk tumor types, he added.
“It’s an important question we are facing as clinicians on a daily basis,” he said, responding to an attendee’s query, as shared by session moderator James Douketis, MD, professor of medicine at McMaster University, Hamilton, Ont., regarding possible bleeding risks in certain genitourinary cancers.
A recent meta-analysis published in Nature, for example, noted that, in the SELECT-D trial, rivaroxaban was associated with significantly higher incidence of clinically relevant nonmajor bleeding, most often in bladder and colorectal cancers, and most often at genitourinary and gastrointestinal sites.
Both Dr. Carrier and fellow panelist Michael Streiff, MD, professor of medicine at Johns Hopkins University and medical director at the Johns Hopkins Hospital Special Coagulation Laboratory, Baltimore, said they approach DOAC use cautiously, but don’t rule it out entirely, in patients with unresected genitourinary tumors that could pose a risk of bleeding.
“It’s worth mentioning and being cautious. In my own personal practice, I’m very careful with unresected urothelial-type tumors or, for example, bladder cancer, for the same reason as [with] unresected luminal GI tumors,” Dr. Carrier said, adding that he’s also mindful that patients with nephropathy were excluded from U.S. DOAC trials because of bleeding risk.
He said he sometimes tries a LMWH challenge first in higher-risk patients, and then might try a DOAC if no bleeding occurs.
“But it certainly is controversial,” he noted.
Dr. Streiff added that he also worries less with genitourinary cancers than with upper GI lesions because “the signals weren’t as big as in GI” cancers, but he noted that “the drugs are going out through the kidneys ... so I’m cautious in those populations.”
“So caution, but not complete exclusion, is the operative management,” Dr. Douketis said, summarizing the panelists’ consensus.
Dr. Carrier reported clinical trial or advisory board participation for Bayer, Pfizer, Servier, Leo Pharma, and/or BMS.
Primary thromboprophylaxis is feasible and worth considering for high-risk ambulatory patients with cancer who are initiating systemic chemotherapy, according to Marc Carrier, MD.
Risk scores can identify patients at high risk for venous thromboembolism (VTE), and treatments that are effective and associated with low bleeding risk are available, Dr. Carrier explained at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
However, caution is advised in patients with certain types of cancer, including some gastrointestinal and genitourinary cancers, because of the possibility of increased major and clinically relevant nonmajor bleeding risk, he said.
VTE and cancer
VTE is relatively rare in the general population, occurring in about 1 or 2 per 1,000 people annually. The risk increases 4.1-fold in patients with cancer, and 6.5-fold in patients with cancer receiving chemotherapy.
“So just putting these numbers together, we’re no longer talking about 1 in 1,000, but 1 in 200, so [this is] something that is very common among cancer patients,” said Dr. Carrier, a professor at the University of Ottawa and chief of the division of hematology at The Ottawa Hospital.
The mortality rate associated with cancer-associated thrombosis is about 9%, comparable to that associated with infection in the cancer outpatient setting, which underscores the importance of educating patients about the signs and symptoms of VTE so they can seek medical treatment quickly if necessary, he added.
It may also be useful to discuss prophylaxis or other ways to prevent venous thromboembolic complications with certain patients, he said, noting that in an observational cohort study of nearly 600 patients at the University of Ottawa, 25% of those initiating chemotherapy were identified as intermediate or high risk using the validated Khorana risk score, and thus would likely benefit from thromboprophylaxis.
Risk assessment
The Khorana risk score assesses VTE risk based on cancer site, blood counts, and body mass index. It is simple to use and has been validated in more than 20,000 people in multiple countries, Dr. Carrier said.
In a well-known validation study, Ay et al. showed a VTE complication rate of 10% in patients with a Khorana risk score of 2 or higher who were followed up to 6 months.
“This is huge,” Dr. Carrier stressed. “This is much higher than what we tolerate for all sorts of different populations for which we would recommend anticoagulation or thromboprophylaxis.”
The question is whether the risk score can be helpful in a real-world clinic setting, he said, adding: “I’d like to think the answer to that is yes.”
In the University of Ottawa cohort study, 11% of high-risk patients experienced a VTE complication, compared with 4% of those with lower risk, suggesting that the validation data for the Khorana risk score is not only accurate, it is “actually applicable in real-world practice, and you can use it in your own center,” he said.
Further, recent studies have demonstrated that treatment based on Khorana risk score assessment reduces VTE complications.
Prophylaxis options
Low-molecular-weight heparin (LMWH) has been shown in several studies to be associated with a significant relative VTE risk reduction in patients with cancer initiating chemotherapy – with only a slight, nonsignificant increase in the risk of major bleeding.
However, the absolute benefit was small, and LMWH is “parenteral, relatively costly, and, based on that, although we showed relatively good risk-benefit ratio, it never really got translated to clinical practice,” Dr. Carrier said.
In fact, a 2015 American Society of Clinical Oncology guidelines update recommended against routine thromboprophylaxis in this setting, but stated that it could be considered in select high-risk patients identified using a validated risk-assessment tool.
The guidelines noted that “individual risk factors such as biomarkers and cancer site don’t reliably identify high-risk patients.”
More recent data provide additional support for risk assessment and treatment based on Khorana risk score of 2 or higher.
The AVERT trial, for which Dr. Carrier was the first author, showed that the direct-acting oral anticoagulant (DOAC) apixaban reduced VTE incidence, compared with placebo, in patients with Khorana score of 2 or higher (4.2% vs. 10.2%; hazard ratio, 0.41 overall, and 1.0 vs. 7.3; HR, 0.14 on treatment), and the CASSINI trial showed that another DOAC, rivaroxaban, reduced VTE incidence, compared with placebo, in those with Khorana score of 2 or higher (5.9 vs. 6.7; HR, 0.6 overall, and 2.6 vs. 6.4; HR, 0.40 on treatment). The differences in the on-treatment populations were statistically significant.
The two trials, which included a variety of tumor types, showed similar rates of major bleeding, with an absolute difference of about 1% between treatment and placebo, which was not statistically significant in the on-treatment analyses (HR, 1.89 in AVERT and HR, 1.96 in CASSINI).
A systematic review of these trials showed an overall significant decrease in VTE complication risk with treatment in high-risk patients, and a nonstatistically significant major bleeding risk increase.
Based on these findings, ASCO guidelines were updated in 2020 to state that “routine thromboprophylaxis should not be offered to all patients with cancer. ... However, high-risk outpatients with cancer may be offered thromboprophylaxis with apixaban, rivaroxaban or LMWH, providing there are no significant risk factors for bleeding or drug-drug interactions, and after having a full discussion with patients ... to make sure they understand the risk-benefit ratio and the rationale for that particular recommendation,” he said.
Real-world implementation
Implementing this approach in the clinic setting requires a practical model, such as the Venous Thromboembolism Prevention in the Ambulatory Cancer Clinic (VTEPACC) program, a prospective quality improvement research initiative developed in collaboration with the Jeffords Institute for Quality at the University of Vermont Medical Center and described in a recent report, Dr. Carrier said.
The “Vermont model” is “really a comprehensive model that includes identifying patients with the electronic medical records, gathering the formal education and insight from other health care providers like pharmacists and nurses in order to really come up with personalized care for your patients,” he explained.
In 918 outpatients with cancer who were included in the program, VTE awareness increased from less than 5% before VTEPACC to nearly 82% during the implementation phase and 94.7% after 2 years, with nearly 94% of high-risk patients receiving VTE prophylaxis at that time.
“So we can certainly do that in our own center.” he said. “It’s a matter of coming up with the model and making sure that the patients are seen at the right time.”
Given the high frequency of VTE in patients with cancer initiating chemotherapy, the usefulness of risk scores such as the Khorana risk score for identifying those at high risk, and the availability of safe and effective interventions for reducing risk, “we should probably use the data and incorporate them into clinical practice by implementation of programs for primary prevention,” he said.
A word of caution
Caution is warranted, however, when it comes to using DOACs in patients with higher-risk or potentially higher-risk tumor types, he added.
“It’s an important question we are facing as clinicians on a daily basis,” he said, responding to an attendee’s query, as shared by session moderator James Douketis, MD, professor of medicine at McMaster University, Hamilton, Ont., regarding possible bleeding risks in certain genitourinary cancers.
A recent meta-analysis published in Nature, for example, noted that, in the SELECT-D trial, rivaroxaban was associated with significantly higher incidence of clinically relevant nonmajor bleeding, most often in bladder and colorectal cancers, and most often at genitourinary and gastrointestinal sites.
Both Dr. Carrier and fellow panelist Michael Streiff, MD, professor of medicine at Johns Hopkins University and medical director at the Johns Hopkins Hospital Special Coagulation Laboratory, Baltimore, said they approach DOAC use cautiously, but don’t rule it out entirely, in patients with unresected genitourinary tumors that could pose a risk of bleeding.
“It’s worth mentioning and being cautious. In my own personal practice, I’m very careful with unresected urothelial-type tumors or, for example, bladder cancer, for the same reason as [with] unresected luminal GI tumors,” Dr. Carrier said, adding that he’s also mindful that patients with nephropathy were excluded from U.S. DOAC trials because of bleeding risk.
He said he sometimes tries a LMWH challenge first in higher-risk patients, and then might try a DOAC if no bleeding occurs.
“But it certainly is controversial,” he noted.
Dr. Streiff added that he also worries less with genitourinary cancers than with upper GI lesions because “the signals weren’t as big as in GI” cancers, but he noted that “the drugs are going out through the kidneys ... so I’m cautious in those populations.”
“So caution, but not complete exclusion, is the operative management,” Dr. Douketis said, summarizing the panelists’ consensus.
Dr. Carrier reported clinical trial or advisory board participation for Bayer, Pfizer, Servier, Leo Pharma, and/or BMS.
Primary thromboprophylaxis is feasible and worth considering for high-risk ambulatory patients with cancer who are initiating systemic chemotherapy, according to Marc Carrier, MD.
Risk scores can identify patients at high risk for venous thromboembolism (VTE), and treatments that are effective and associated with low bleeding risk are available, Dr. Carrier explained at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
However, caution is advised in patients with certain types of cancer, including some gastrointestinal and genitourinary cancers, because of the possibility of increased major and clinically relevant nonmajor bleeding risk, he said.
VTE and cancer
VTE is relatively rare in the general population, occurring in about 1 or 2 per 1,000 people annually. The risk increases 4.1-fold in patients with cancer, and 6.5-fold in patients with cancer receiving chemotherapy.
“So just putting these numbers together, we’re no longer talking about 1 in 1,000, but 1 in 200, so [this is] something that is very common among cancer patients,” said Dr. Carrier, a professor at the University of Ottawa and chief of the division of hematology at The Ottawa Hospital.
The mortality rate associated with cancer-associated thrombosis is about 9%, comparable to that associated with infection in the cancer outpatient setting, which underscores the importance of educating patients about the signs and symptoms of VTE so they can seek medical treatment quickly if necessary, he added.
It may also be useful to discuss prophylaxis or other ways to prevent venous thromboembolic complications with certain patients, he said, noting that in an observational cohort study of nearly 600 patients at the University of Ottawa, 25% of those initiating chemotherapy were identified as intermediate or high risk using the validated Khorana risk score, and thus would likely benefit from thromboprophylaxis.
Risk assessment
The Khorana risk score assesses VTE risk based on cancer site, blood counts, and body mass index. It is simple to use and has been validated in more than 20,000 people in multiple countries, Dr. Carrier said.
In a well-known validation study, Ay et al. showed a VTE complication rate of 10% in patients with a Khorana risk score of 2 or higher who were followed up to 6 months.
“This is huge,” Dr. Carrier stressed. “This is much higher than what we tolerate for all sorts of different populations for which we would recommend anticoagulation or thromboprophylaxis.”
The question is whether the risk score can be helpful in a real-world clinic setting, he said, adding: “I’d like to think the answer to that is yes.”
In the University of Ottawa cohort study, 11% of high-risk patients experienced a VTE complication, compared with 4% of those with lower risk, suggesting that the validation data for the Khorana risk score is not only accurate, it is “actually applicable in real-world practice, and you can use it in your own center,” he said.
Further, recent studies have demonstrated that treatment based on Khorana risk score assessment reduces VTE complications.
Prophylaxis options
Low-molecular-weight heparin (LMWH) has been shown in several studies to be associated with a significant relative VTE risk reduction in patients with cancer initiating chemotherapy – with only a slight, nonsignificant increase in the risk of major bleeding.
However, the absolute benefit was small, and LMWH is “parenteral, relatively costly, and, based on that, although we showed relatively good risk-benefit ratio, it never really got translated to clinical practice,” Dr. Carrier said.
In fact, a 2015 American Society of Clinical Oncology guidelines update recommended against routine thromboprophylaxis in this setting, but stated that it could be considered in select high-risk patients identified using a validated risk-assessment tool.
The guidelines noted that “individual risk factors such as biomarkers and cancer site don’t reliably identify high-risk patients.”
More recent data provide additional support for risk assessment and treatment based on Khorana risk score of 2 or higher.
The AVERT trial, for which Dr. Carrier was the first author, showed that the direct-acting oral anticoagulant (DOAC) apixaban reduced VTE incidence, compared with placebo, in patients with Khorana score of 2 or higher (4.2% vs. 10.2%; hazard ratio, 0.41 overall, and 1.0 vs. 7.3; HR, 0.14 on treatment), and the CASSINI trial showed that another DOAC, rivaroxaban, reduced VTE incidence, compared with placebo, in those with Khorana score of 2 or higher (5.9 vs. 6.7; HR, 0.6 overall, and 2.6 vs. 6.4; HR, 0.40 on treatment). The differences in the on-treatment populations were statistically significant.
The two trials, which included a variety of tumor types, showed similar rates of major bleeding, with an absolute difference of about 1% between treatment and placebo, which was not statistically significant in the on-treatment analyses (HR, 1.89 in AVERT and HR, 1.96 in CASSINI).
A systematic review of these trials showed an overall significant decrease in VTE complication risk with treatment in high-risk patients, and a nonstatistically significant major bleeding risk increase.
Based on these findings, ASCO guidelines were updated in 2020 to state that “routine thromboprophylaxis should not be offered to all patients with cancer. ... However, high-risk outpatients with cancer may be offered thromboprophylaxis with apixaban, rivaroxaban or LMWH, providing there are no significant risk factors for bleeding or drug-drug interactions, and after having a full discussion with patients ... to make sure they understand the risk-benefit ratio and the rationale for that particular recommendation,” he said.
Real-world implementation
Implementing this approach in the clinic setting requires a practical model, such as the Venous Thromboembolism Prevention in the Ambulatory Cancer Clinic (VTEPACC) program, a prospective quality improvement research initiative developed in collaboration with the Jeffords Institute for Quality at the University of Vermont Medical Center and described in a recent report, Dr. Carrier said.
The “Vermont model” is “really a comprehensive model that includes identifying patients with the electronic medical records, gathering the formal education and insight from other health care providers like pharmacists and nurses in order to really come up with personalized care for your patients,” he explained.
In 918 outpatients with cancer who were included in the program, VTE awareness increased from less than 5% before VTEPACC to nearly 82% during the implementation phase and 94.7% after 2 years, with nearly 94% of high-risk patients receiving VTE prophylaxis at that time.
“So we can certainly do that in our own center.” he said. “It’s a matter of coming up with the model and making sure that the patients are seen at the right time.”
Given the high frequency of VTE in patients with cancer initiating chemotherapy, the usefulness of risk scores such as the Khorana risk score for identifying those at high risk, and the availability of safe and effective interventions for reducing risk, “we should probably use the data and incorporate them into clinical practice by implementation of programs for primary prevention,” he said.
A word of caution
Caution is warranted, however, when it comes to using DOACs in patients with higher-risk or potentially higher-risk tumor types, he added.
“It’s an important question we are facing as clinicians on a daily basis,” he said, responding to an attendee’s query, as shared by session moderator James Douketis, MD, professor of medicine at McMaster University, Hamilton, Ont., regarding possible bleeding risks in certain genitourinary cancers.
A recent meta-analysis published in Nature, for example, noted that, in the SELECT-D trial, rivaroxaban was associated with significantly higher incidence of clinically relevant nonmajor bleeding, most often in bladder and colorectal cancers, and most often at genitourinary and gastrointestinal sites.
Both Dr. Carrier and fellow panelist Michael Streiff, MD, professor of medicine at Johns Hopkins University and medical director at the Johns Hopkins Hospital Special Coagulation Laboratory, Baltimore, said they approach DOAC use cautiously, but don’t rule it out entirely, in patients with unresected genitourinary tumors that could pose a risk of bleeding.
“It’s worth mentioning and being cautious. In my own personal practice, I’m very careful with unresected urothelial-type tumors or, for example, bladder cancer, for the same reason as [with] unresected luminal GI tumors,” Dr. Carrier said, adding that he’s also mindful that patients with nephropathy were excluded from U.S. DOAC trials because of bleeding risk.
He said he sometimes tries a LMWH challenge first in higher-risk patients, and then might try a DOAC if no bleeding occurs.
“But it certainly is controversial,” he noted.
Dr. Streiff added that he also worries less with genitourinary cancers than with upper GI lesions because “the signals weren’t as big as in GI” cancers, but he noted that “the drugs are going out through the kidneys ... so I’m cautious in those populations.”
“So caution, but not complete exclusion, is the operative management,” Dr. Douketis said, summarizing the panelists’ consensus.
Dr. Carrier reported clinical trial or advisory board participation for Bayer, Pfizer, Servier, Leo Pharma, and/or BMS.
FROM THE THSNA BIENNIAL SUMMIT
Obesity, hypoxia predict severity in children with COVID-19
based on data from 281 patients at 8 locations.
Manifestations of COVID-19 in children include respiratory disease similar to that seen in adults, but the full spectrum of disease in children has been studied mainly in single settings or with a focus on one clinical manifestation, wrote Danielle M. Fernandes, MD, of Albert Einstein College of Medicine, New York, and colleagues.
In a study published in the Journal of Pediatrics, the researchers identified 281 children hospitalized with COVID-19 and/or multisystem inflammatory syndrome in children (MIS-C) at 8 sites in Connecticut, New Jersey, and New York. A total of 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations of illness including 32 patients with gastrointestinal problems, 21 infants with fever, 6 cases of neurologic disease, 6 cases of diabetic ketoacidosis, and 4 patients with other indications. The median age of the patients was 10 years, 60% were male, 51% were Hispanic, and 23% were non-Hispanic Black. The most common comorbidities were obesity (34%) and asthma (14%).
Independent predictors of disease severity in children found
After controlling for multiple variables, obesity and hypoxia at hospital admission were significant independent predictors of severe respiratory disease, with odds ratios of 3.39 and 4.01, respectively. In addition, lower absolute lymphocyte count (OR, 8.33 per unit decrease in 109 cells/L) and higher C-reactive protein (OR, 1.06 per unit increase in mg/dL) were significantly predictive of severe MIS-C (P = .001 and P = .017, respectively).
“The association between weight and severe respiratory COVID-19 is consistent with the adult literature; however, the mechanisms of this association require further study,” Dr. Fernandes and associates noted.
Overall, children with MIS-C were significantly more likely to be non-Hispanic Black, compared with children with respiratory disease, an 18% difference. However, neither race/ethnicity nor socioeconomic status were significant predictors of disease severity, the researchers wrote.
During the study period, 7 patients (2%) died and 114 (41%) were admitted to the ICU.
“We found a wide array of clinical manifestations in children and youth hospitalized with SARS-CoV-2,” Dr. Fernandes and associates wrote. Notably, gastrointestinal symptoms, ocular symptoms, and dermatologic symptoms have rarely been noted in adults with COVID-19, but occurred in more than 30% of the pediatric patients.
“We also found that SARS-CoV-2 can be an incidental finding in a substantial number of hospitalized pediatric patients,” the researchers said.
The findings were limited by several factors including a population of patients only from Connecticut, New Jersey, and New York, and the possibility that decisions on hospital and ICU admission may have varied by location, the researchers said. In addition, approaches may have varied in the absence of data on the optimal treatment of MIS-C.
“This study builds on the growing body of evidence showing that mortality in hospitalized pediatric patients is low, compared with adults,” Dr. Fernandes and associates said. “However, it highlights that the young population is not universally spared from morbidity, and that even previously healthy children and youth can develop severe disease requiring supportive therapy.”
Findings confirm other clinical experience
The study was important to show that, “although most children are spared severe illness from COVID-19, some children are hospitalized both with acute COVID-19 respiratory disease, with MIS-C and with a range of other complications,” Adrienne Randolph, MD, of Boston Children’s Hospital and Harvard Medical School, Boston, said in an interview.
Dr. Randolph said she was not surprised by the study findings, “as we are also seeing these types of complications at Boston Children’s Hospital where I work.”
Additional research is needed on the outcomes of these patients, “especially the longer-term sequelae of having COVID-19 or MIS-C early in life,” she emphasized.
The take-home message to clinicians from the findings at this time is to be aware that children and adolescents can become severely ill from COVID-19–related complications, said Dr. Randolph. “Some of the laboratory values on presentation appear to be associated with disease severity.”
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Randolph disclosed funding from the Centers for Disease Control and Prevention to lead the Overcoming COVID-19 Study in U.S. Children and Adults.
SOURCE: Fernandes DM et al. J Pediatr. 2020 Nov 13. doi: 10.1016/j.jpeds.2020.11.016.
based on data from 281 patients at 8 locations.
Manifestations of COVID-19 in children include respiratory disease similar to that seen in adults, but the full spectrum of disease in children has been studied mainly in single settings or with a focus on one clinical manifestation, wrote Danielle M. Fernandes, MD, of Albert Einstein College of Medicine, New York, and colleagues.
In a study published in the Journal of Pediatrics, the researchers identified 281 children hospitalized with COVID-19 and/or multisystem inflammatory syndrome in children (MIS-C) at 8 sites in Connecticut, New Jersey, and New York. A total of 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations of illness including 32 patients with gastrointestinal problems, 21 infants with fever, 6 cases of neurologic disease, 6 cases of diabetic ketoacidosis, and 4 patients with other indications. The median age of the patients was 10 years, 60% were male, 51% were Hispanic, and 23% were non-Hispanic Black. The most common comorbidities were obesity (34%) and asthma (14%).
Independent predictors of disease severity in children found
After controlling for multiple variables, obesity and hypoxia at hospital admission were significant independent predictors of severe respiratory disease, with odds ratios of 3.39 and 4.01, respectively. In addition, lower absolute lymphocyte count (OR, 8.33 per unit decrease in 109 cells/L) and higher C-reactive protein (OR, 1.06 per unit increase in mg/dL) were significantly predictive of severe MIS-C (P = .001 and P = .017, respectively).
“The association between weight and severe respiratory COVID-19 is consistent with the adult literature; however, the mechanisms of this association require further study,” Dr. Fernandes and associates noted.
Overall, children with MIS-C were significantly more likely to be non-Hispanic Black, compared with children with respiratory disease, an 18% difference. However, neither race/ethnicity nor socioeconomic status were significant predictors of disease severity, the researchers wrote.
During the study period, 7 patients (2%) died and 114 (41%) were admitted to the ICU.
“We found a wide array of clinical manifestations in children and youth hospitalized with SARS-CoV-2,” Dr. Fernandes and associates wrote. Notably, gastrointestinal symptoms, ocular symptoms, and dermatologic symptoms have rarely been noted in adults with COVID-19, but occurred in more than 30% of the pediatric patients.
“We also found that SARS-CoV-2 can be an incidental finding in a substantial number of hospitalized pediatric patients,” the researchers said.
The findings were limited by several factors including a population of patients only from Connecticut, New Jersey, and New York, and the possibility that decisions on hospital and ICU admission may have varied by location, the researchers said. In addition, approaches may have varied in the absence of data on the optimal treatment of MIS-C.
“This study builds on the growing body of evidence showing that mortality in hospitalized pediatric patients is low, compared with adults,” Dr. Fernandes and associates said. “However, it highlights that the young population is not universally spared from morbidity, and that even previously healthy children and youth can develop severe disease requiring supportive therapy.”
Findings confirm other clinical experience
The study was important to show that, “although most children are spared severe illness from COVID-19, some children are hospitalized both with acute COVID-19 respiratory disease, with MIS-C and with a range of other complications,” Adrienne Randolph, MD, of Boston Children’s Hospital and Harvard Medical School, Boston, said in an interview.
Dr. Randolph said she was not surprised by the study findings, “as we are also seeing these types of complications at Boston Children’s Hospital where I work.”
Additional research is needed on the outcomes of these patients, “especially the longer-term sequelae of having COVID-19 or MIS-C early in life,” she emphasized.
The take-home message to clinicians from the findings at this time is to be aware that children and adolescents can become severely ill from COVID-19–related complications, said Dr. Randolph. “Some of the laboratory values on presentation appear to be associated with disease severity.”
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Randolph disclosed funding from the Centers for Disease Control and Prevention to lead the Overcoming COVID-19 Study in U.S. Children and Adults.
SOURCE: Fernandes DM et al. J Pediatr. 2020 Nov 13. doi: 10.1016/j.jpeds.2020.11.016.
based on data from 281 patients at 8 locations.
Manifestations of COVID-19 in children include respiratory disease similar to that seen in adults, but the full spectrum of disease in children has been studied mainly in single settings or with a focus on one clinical manifestation, wrote Danielle M. Fernandes, MD, of Albert Einstein College of Medicine, New York, and colleagues.
In a study published in the Journal of Pediatrics, the researchers identified 281 children hospitalized with COVID-19 and/or multisystem inflammatory syndrome in children (MIS-C) at 8 sites in Connecticut, New Jersey, and New York. A total of 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations of illness including 32 patients with gastrointestinal problems, 21 infants with fever, 6 cases of neurologic disease, 6 cases of diabetic ketoacidosis, and 4 patients with other indications. The median age of the patients was 10 years, 60% were male, 51% were Hispanic, and 23% were non-Hispanic Black. The most common comorbidities were obesity (34%) and asthma (14%).
Independent predictors of disease severity in children found
After controlling for multiple variables, obesity and hypoxia at hospital admission were significant independent predictors of severe respiratory disease, with odds ratios of 3.39 and 4.01, respectively. In addition, lower absolute lymphocyte count (OR, 8.33 per unit decrease in 109 cells/L) and higher C-reactive protein (OR, 1.06 per unit increase in mg/dL) were significantly predictive of severe MIS-C (P = .001 and P = .017, respectively).
“The association between weight and severe respiratory COVID-19 is consistent with the adult literature; however, the mechanisms of this association require further study,” Dr. Fernandes and associates noted.
Overall, children with MIS-C were significantly more likely to be non-Hispanic Black, compared with children with respiratory disease, an 18% difference. However, neither race/ethnicity nor socioeconomic status were significant predictors of disease severity, the researchers wrote.
During the study period, 7 patients (2%) died and 114 (41%) were admitted to the ICU.
“We found a wide array of clinical manifestations in children and youth hospitalized with SARS-CoV-2,” Dr. Fernandes and associates wrote. Notably, gastrointestinal symptoms, ocular symptoms, and dermatologic symptoms have rarely been noted in adults with COVID-19, but occurred in more than 30% of the pediatric patients.
“We also found that SARS-CoV-2 can be an incidental finding in a substantial number of hospitalized pediatric patients,” the researchers said.
The findings were limited by several factors including a population of patients only from Connecticut, New Jersey, and New York, and the possibility that decisions on hospital and ICU admission may have varied by location, the researchers said. In addition, approaches may have varied in the absence of data on the optimal treatment of MIS-C.
“This study builds on the growing body of evidence showing that mortality in hospitalized pediatric patients is low, compared with adults,” Dr. Fernandes and associates said. “However, it highlights that the young population is not universally spared from morbidity, and that even previously healthy children and youth can develop severe disease requiring supportive therapy.”
Findings confirm other clinical experience
The study was important to show that, “although most children are spared severe illness from COVID-19, some children are hospitalized both with acute COVID-19 respiratory disease, with MIS-C and with a range of other complications,” Adrienne Randolph, MD, of Boston Children’s Hospital and Harvard Medical School, Boston, said in an interview.
Dr. Randolph said she was not surprised by the study findings, “as we are also seeing these types of complications at Boston Children’s Hospital where I work.”
Additional research is needed on the outcomes of these patients, “especially the longer-term sequelae of having COVID-19 or MIS-C early in life,” she emphasized.
The take-home message to clinicians from the findings at this time is to be aware that children and adolescents can become severely ill from COVID-19–related complications, said Dr. Randolph. “Some of the laboratory values on presentation appear to be associated with disease severity.”
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Randolph disclosed funding from the Centers for Disease Control and Prevention to lead the Overcoming COVID-19 Study in U.S. Children and Adults.
SOURCE: Fernandes DM et al. J Pediatr. 2020 Nov 13. doi: 10.1016/j.jpeds.2020.11.016.
FROM THE JOURNAL OF PEDIATRICS
Diabetic retinopathy may predict greater risk of COVID-19 severity
Risk of intubation for COVID-19 in very sick hospitalized patients was increased over fivefold in those with diabetic retinopathy, compared with those without, in a small single-center study from the United Kingdom.
Importantly, the risk of intubation was independent of conventional risk factors for poor COVID-19 outcomes.
“People with preexisting diabetes-related vascular damage, such as retinopathy, might be predisposed to a more severe form of COVID-19 requiring ventilation in the intensive therapy unit,” said lead investigator Janaka Karalliedde, MBBS, PhD.
Dr. Karalliedde and colleagues note that this is “the first description of diabetic retinopathy as a potential risk factor for poor COVID-19 outcomes.”
“For this reason, looking for the presence or history of retinopathy or other vascular complications of diabetes may help health care professionals identify patients at high risk of severe COVID-19,” added Dr. Karalliedde, of Guy’s and St Thomas’ NHS Foundation Trust, London.
The study was published online in Diabetes Research and Clinical Practice.
Preexisting diabetic retinopathy and COVID-19 outcomes
The prevalence of diabetic retinopathy is thought to be around 55% in people with type 1 diabetes and 30% in people with type 2 diabetes, on average.
Dr. Karalliedde is part of a research group at King’s College London that has been focused on how vascular disease may predispose to more severe COVID-19.
“COVID-19 affects the blood vessels all over the body,” he said, so they wondered whether having preexisting retinopathy “would predispose to a severe manifestation of COVID-19.”
The observational study included 187 patients with diabetes (179 patients with type 2 diabetes and 8 patients with type 1 diabetes) hospitalized with COVID-19 at Guy’s and St Thomas’ NHS Foundation Trust between March 12 and April 7 (the peak of the first wave of the pandemic in the United Kingdom).
“It was an ethnically diverse population who were very sick and provides a clinical observation of real life,” Dr. Karalliedde said.
Nearly half of patients were African Caribbean (44%), 39% were White, and 17% were of other ethnicities, including 8% who were Asian. The mean age of the cohort was 68 years (range, 22-97 years), and 60% were men.
Diabetic retinopathy was reported in 67 (36%) patients, of whom 80% had background retinopathy and 20% had more advanced retinopathy.
They then looked at whether the presence of retinopathy was associated with a more severe manifestation of COVID-19 as defined by the need for tracheal intubation.
Of the 187 patients, 26% were intubated and 45% of these patients had diabetic retinopathy.
The analysis showed those with diabetic retinopathy had an over-fivefold increased risk for intubation (odds ratio, 5.81; 95% confidence interval, 1.37-24.66).
Of the entire cohort, 32% of patients died, although no association was observed between retinopathy and mortality.
“A greater number of diabetes patients with COVID-19 ended up on the intensive therapy unit. Upon multivariate analysis, we found retinopathy was independently associated with ending up on the intensive therapy unit,” stressed Dr. Karalliedde.
However, they noted that, “due to the cross-sectional design of our study, we cannot prove causality [between retinopathy and intubation]. Further studies are required to understand the mechanisms that explain the associations between retinopathy and other indices of microangiopathy with severe COVID-19.”
A version of this article originally appeared on Medscape.com.
Risk of intubation for COVID-19 in very sick hospitalized patients was increased over fivefold in those with diabetic retinopathy, compared with those without, in a small single-center study from the United Kingdom.
Importantly, the risk of intubation was independent of conventional risk factors for poor COVID-19 outcomes.
“People with preexisting diabetes-related vascular damage, such as retinopathy, might be predisposed to a more severe form of COVID-19 requiring ventilation in the intensive therapy unit,” said lead investigator Janaka Karalliedde, MBBS, PhD.
Dr. Karalliedde and colleagues note that this is “the first description of diabetic retinopathy as a potential risk factor for poor COVID-19 outcomes.”
“For this reason, looking for the presence or history of retinopathy or other vascular complications of diabetes may help health care professionals identify patients at high risk of severe COVID-19,” added Dr. Karalliedde, of Guy’s and St Thomas’ NHS Foundation Trust, London.
The study was published online in Diabetes Research and Clinical Practice.
Preexisting diabetic retinopathy and COVID-19 outcomes
The prevalence of diabetic retinopathy is thought to be around 55% in people with type 1 diabetes and 30% in people with type 2 diabetes, on average.
Dr. Karalliedde is part of a research group at King’s College London that has been focused on how vascular disease may predispose to more severe COVID-19.
“COVID-19 affects the blood vessels all over the body,” he said, so they wondered whether having preexisting retinopathy “would predispose to a severe manifestation of COVID-19.”
The observational study included 187 patients with diabetes (179 patients with type 2 diabetes and 8 patients with type 1 diabetes) hospitalized with COVID-19 at Guy’s and St Thomas’ NHS Foundation Trust between March 12 and April 7 (the peak of the first wave of the pandemic in the United Kingdom).
“It was an ethnically diverse population who were very sick and provides a clinical observation of real life,” Dr. Karalliedde said.
Nearly half of patients were African Caribbean (44%), 39% were White, and 17% were of other ethnicities, including 8% who were Asian. The mean age of the cohort was 68 years (range, 22-97 years), and 60% were men.
Diabetic retinopathy was reported in 67 (36%) patients, of whom 80% had background retinopathy and 20% had more advanced retinopathy.
They then looked at whether the presence of retinopathy was associated with a more severe manifestation of COVID-19 as defined by the need for tracheal intubation.
Of the 187 patients, 26% were intubated and 45% of these patients had diabetic retinopathy.
The analysis showed those with diabetic retinopathy had an over-fivefold increased risk for intubation (odds ratio, 5.81; 95% confidence interval, 1.37-24.66).
Of the entire cohort, 32% of patients died, although no association was observed between retinopathy and mortality.
“A greater number of diabetes patients with COVID-19 ended up on the intensive therapy unit. Upon multivariate analysis, we found retinopathy was independently associated with ending up on the intensive therapy unit,” stressed Dr. Karalliedde.
However, they noted that, “due to the cross-sectional design of our study, we cannot prove causality [between retinopathy and intubation]. Further studies are required to understand the mechanisms that explain the associations between retinopathy and other indices of microangiopathy with severe COVID-19.”
A version of this article originally appeared on Medscape.com.
Risk of intubation for COVID-19 in very sick hospitalized patients was increased over fivefold in those with diabetic retinopathy, compared with those without, in a small single-center study from the United Kingdom.
Importantly, the risk of intubation was independent of conventional risk factors for poor COVID-19 outcomes.
“People with preexisting diabetes-related vascular damage, such as retinopathy, might be predisposed to a more severe form of COVID-19 requiring ventilation in the intensive therapy unit,” said lead investigator Janaka Karalliedde, MBBS, PhD.
Dr. Karalliedde and colleagues note that this is “the first description of diabetic retinopathy as a potential risk factor for poor COVID-19 outcomes.”
“For this reason, looking for the presence or history of retinopathy or other vascular complications of diabetes may help health care professionals identify patients at high risk of severe COVID-19,” added Dr. Karalliedde, of Guy’s and St Thomas’ NHS Foundation Trust, London.
The study was published online in Diabetes Research and Clinical Practice.
Preexisting diabetic retinopathy and COVID-19 outcomes
The prevalence of diabetic retinopathy is thought to be around 55% in people with type 1 diabetes and 30% in people with type 2 diabetes, on average.
Dr. Karalliedde is part of a research group at King’s College London that has been focused on how vascular disease may predispose to more severe COVID-19.
“COVID-19 affects the blood vessels all over the body,” he said, so they wondered whether having preexisting retinopathy “would predispose to a severe manifestation of COVID-19.”
The observational study included 187 patients with diabetes (179 patients with type 2 diabetes and 8 patients with type 1 diabetes) hospitalized with COVID-19 at Guy’s and St Thomas’ NHS Foundation Trust between March 12 and April 7 (the peak of the first wave of the pandemic in the United Kingdom).
“It was an ethnically diverse population who were very sick and provides a clinical observation of real life,” Dr. Karalliedde said.
Nearly half of patients were African Caribbean (44%), 39% were White, and 17% were of other ethnicities, including 8% who were Asian. The mean age of the cohort was 68 years (range, 22-97 years), and 60% were men.
Diabetic retinopathy was reported in 67 (36%) patients, of whom 80% had background retinopathy and 20% had more advanced retinopathy.
They then looked at whether the presence of retinopathy was associated with a more severe manifestation of COVID-19 as defined by the need for tracheal intubation.
Of the 187 patients, 26% were intubated and 45% of these patients had diabetic retinopathy.
The analysis showed those with diabetic retinopathy had an over-fivefold increased risk for intubation (odds ratio, 5.81; 95% confidence interval, 1.37-24.66).
Of the entire cohort, 32% of patients died, although no association was observed between retinopathy and mortality.
“A greater number of diabetes patients with COVID-19 ended up on the intensive therapy unit. Upon multivariate analysis, we found retinopathy was independently associated with ending up on the intensive therapy unit,” stressed Dr. Karalliedde.
However, they noted that, “due to the cross-sectional design of our study, we cannot prove causality [between retinopathy and intubation]. Further studies are required to understand the mechanisms that explain the associations between retinopathy and other indices of microangiopathy with severe COVID-19.”
A version of this article originally appeared on Medscape.com.
COVID-19 vaccine distribution could start in 2 weeks, Pence says
Initial doses of a coronavirus vaccine could be sent out as early as mid-December, Vice President Mike Pence told governors during a call on Monday.
The distribution process could start during the week of Dec. 14, according to audio of a White House Coronavirus Task Force call obtained by CBS News. The call focused on the timeline of vaccine approval and distribution.
“With this morning’s news that Moderna is joining Pfizer in submitting an emergency-use authorization [to the Food and Drug Administration], we continue to be on pace,” Pence said.
The FDA is scheduled to make a decision about Pfizer’s emergency use authorization after an advisory panel meets on Dec. 10 to review the company’s application. FDA Commissioner Stephen Hahn, MD, didn’t commit to the Dec. 14 date, CBS News reported.
“We do all the number crunching ourselves,” Dr. Hahn said. “We look line by line by line on all the data, on all the patients and manufacturing. We do statistical analyses and we come to our own conclusions to support a decision of either thumbs-up or thumbs-down.”
According to a meeting agenda, Pfizer vaccine deliveries should start on Dec. 15, followed by the Moderna vaccine on Dec. 22, CBS News reported.
Between Dec. 13-19, Pfizer is slated to deliver 6.4 million doses, which is enough to immunize about 3 million people with two shots. An “undetermined number” are reserved for backup doses, the news outlet reported.
During the next week, Pfizer and Moderna are scheduled to produce enough doses to vaccinate an additional 10 million people. By the end of the month, about 30 million people should receive doses.
As vaccines begin to roll out, Mr. Pence said “we have a ways to go” in reassuring the public about immunization. He urged governors to use their “bully pulpit” to educate their states and “develop public confidence” in the vaccines.
During the call, Anthony Fauci, MD, director of the National Institute for Allergy and Infectious Diseases, supported the safety and efficacy of the vaccines. Although the vaccine development and approval process was accelerated this year, he said, it “does not at all compromise safety, nor does it compromise scientific integrity.”
“Any misrepresentation that the vaccines had government interference or company interference is patently untrue,” he said.
This article first appeared on Medscape.com.
Initial doses of a coronavirus vaccine could be sent out as early as mid-December, Vice President Mike Pence told governors during a call on Monday.
The distribution process could start during the week of Dec. 14, according to audio of a White House Coronavirus Task Force call obtained by CBS News. The call focused on the timeline of vaccine approval and distribution.
“With this morning’s news that Moderna is joining Pfizer in submitting an emergency-use authorization [to the Food and Drug Administration], we continue to be on pace,” Pence said.
The FDA is scheduled to make a decision about Pfizer’s emergency use authorization after an advisory panel meets on Dec. 10 to review the company’s application. FDA Commissioner Stephen Hahn, MD, didn’t commit to the Dec. 14 date, CBS News reported.
“We do all the number crunching ourselves,” Dr. Hahn said. “We look line by line by line on all the data, on all the patients and manufacturing. We do statistical analyses and we come to our own conclusions to support a decision of either thumbs-up or thumbs-down.”
According to a meeting agenda, Pfizer vaccine deliveries should start on Dec. 15, followed by the Moderna vaccine on Dec. 22, CBS News reported.
Between Dec. 13-19, Pfizer is slated to deliver 6.4 million doses, which is enough to immunize about 3 million people with two shots. An “undetermined number” are reserved for backup doses, the news outlet reported.
During the next week, Pfizer and Moderna are scheduled to produce enough doses to vaccinate an additional 10 million people. By the end of the month, about 30 million people should receive doses.
As vaccines begin to roll out, Mr. Pence said “we have a ways to go” in reassuring the public about immunization. He urged governors to use their “bully pulpit” to educate their states and “develop public confidence” in the vaccines.
During the call, Anthony Fauci, MD, director of the National Institute for Allergy and Infectious Diseases, supported the safety and efficacy of the vaccines. Although the vaccine development and approval process was accelerated this year, he said, it “does not at all compromise safety, nor does it compromise scientific integrity.”
“Any misrepresentation that the vaccines had government interference or company interference is patently untrue,” he said.
This article first appeared on Medscape.com.
Initial doses of a coronavirus vaccine could be sent out as early as mid-December, Vice President Mike Pence told governors during a call on Monday.
The distribution process could start during the week of Dec. 14, according to audio of a White House Coronavirus Task Force call obtained by CBS News. The call focused on the timeline of vaccine approval and distribution.
“With this morning’s news that Moderna is joining Pfizer in submitting an emergency-use authorization [to the Food and Drug Administration], we continue to be on pace,” Pence said.
The FDA is scheduled to make a decision about Pfizer’s emergency use authorization after an advisory panel meets on Dec. 10 to review the company’s application. FDA Commissioner Stephen Hahn, MD, didn’t commit to the Dec. 14 date, CBS News reported.
“We do all the number crunching ourselves,” Dr. Hahn said. “We look line by line by line on all the data, on all the patients and manufacturing. We do statistical analyses and we come to our own conclusions to support a decision of either thumbs-up or thumbs-down.”
According to a meeting agenda, Pfizer vaccine deliveries should start on Dec. 15, followed by the Moderna vaccine on Dec. 22, CBS News reported.
Between Dec. 13-19, Pfizer is slated to deliver 6.4 million doses, which is enough to immunize about 3 million people with two shots. An “undetermined number” are reserved for backup doses, the news outlet reported.
During the next week, Pfizer and Moderna are scheduled to produce enough doses to vaccinate an additional 10 million people. By the end of the month, about 30 million people should receive doses.
As vaccines begin to roll out, Mr. Pence said “we have a ways to go” in reassuring the public about immunization. He urged governors to use their “bully pulpit” to educate their states and “develop public confidence” in the vaccines.
During the call, Anthony Fauci, MD, director of the National Institute for Allergy and Infectious Diseases, supported the safety and efficacy of the vaccines. Although the vaccine development and approval process was accelerated this year, he said, it “does not at all compromise safety, nor does it compromise scientific integrity.”
“Any misrepresentation that the vaccines had government interference or company interference is patently untrue,” he said.
This article first appeared on Medscape.com.
Medicare finalizes 2021 physician pay rule with E/M changes
Medicare officials stuck with their plan to increase payments for office visits for primary care and several other specialties that focus on helping patients manage complex conditions such as diabetes. In doing so, Medicare also finalized cuts for other fields, triggering a new wave of protests.
The final version of the 2021 Medicare physician fee schedule was unveiled on the night of Dec. 1. The Centers for Medicare & Medicaid Services posted an unofficial copy of the rule, which will later be published in the Federal Register.
CMS said it completed work on this massive annual review of payments for clinicians later than it usually does because of the demands of the federal response to the COVID-19 pandemic. The 2021 physician fee rule will take effect within a 30-day period instead of the usual 60-day time frame.
The most contentious item proposed for 2021 was a reshuffling of payments among specialties as part of an overhaul of Medicare’s approach to valuing evaluation and management (E/M) services. There was broader support for other aspects of the E/M overhaul, which are intended to cut some of the administrative hassle clinicians face.
“This finalized policy marks the most significant updates to E/M codes in 30 years, reducing burden on doctors imposed by the coding system and rewarding time spent evaluating and managing their patients’ care,” CMS Administrator Seema Verma said in a statement. “In the past, the system has rewarded interventions and procedures over time spent with patients – time taken preventing disease and managing chronic illnesses.”
In the final rule, CMS summarized these results of the E/M changes in Table 106. CMS largely stuck with the approach outlined in a draft rule released in August, with minor changes in the amounts of cuts and increases.
Specialties in line for increases under the 2021 final physician fee schedule include allergy/immunology (9%), endocrinology (16%), family practice (13%), general practice (7%), geriatrics (3%), hematology/oncology (14%), internal medicine (4%), nephrology (6%), physician assistants (8%), psychiatry (7%), rheumatology (15%), and urology (8%).
In line for cuts would be anesthesiology (–8%), cardiac surgery (–8%), emergency medicine (–6%), general surgery (–6%), infectious disease (–4%), neurosurgery (–6%), physical/occupational therapy (–9%), plastic surgery (–7%), radiology (–10%), and thoracic surgery (–8%).
CMS had initially set these changes in 2021 pay in motion in the 2020 physician fee schedule. The agency subsequently faced significant opposition to its plans. Many physician groups sought to waive a “budget-neutral” approach to the E/M overhaul, which makes the offsetting of cuts necessary. They argued this would allow increased compensation for clinicians whose practices focus on office visits without requiring offsetting cuts from other fields of medicine.
The American Medical Association is among those urging Congress to prevent or postpone the payment reductions resulting from Medicare’s budget neutrality requirement as applied to the E/M overhaul.
In a Tuesday statement, AMA President Susan R. Bailey, MD, noted that many physicians are facing “substantial economic hardships due to COVID-19.”
By AMA’s calculations, CMS’ planned 2021 E/M overhaul could result in “a shocking reduction of 10.2% to Medicare payment rates,” according to Bailey’s statement. The AMA strongly supports other aspects of the E/M changes CMS finalized, which Bailey said will result in “simpler and more flexible” coding and documentation.
The Surgical Care Coalition, which represents about a dozen medical specialty associations, is asking members of Congress to block the full implementation of the E/M overhaul.
In a Dec. 1 statement, the coalition urged the passage of a bill (HR 8702) that has been introduced in the House by a bipartisan duo of physicians, Rep. Ami Bera, MD (D-Calif.), and Rep. Larry Bucshon, MD (R-Ind.). Their bill would effectively block the cuts from going into effect on January 1, 2021. It would provide an additional Medicare payment for certain services in 2021 and 2022 if the otherwise applicable payment is less than it would have been in 2020.
The Medicare E/M overhaul “was a dangerous policy even before the pandemic, and enacting it during the worst health care crisis in a century is unconscionable. If Congress fails to act, it will further strain a health care system that’s already been pushed to the brink due to the COVID-19 pandemic and undermine patient care,” said John A. Wilson, MD, president of the American Association of Neurological Surgeons, in a statement.
Also backing the Bera-Bucshon bill is the American College of Emergency Physicians. In a statement on Tuesday, ACEP President Mark Rosenberg, DO, MBA, urged Congress to act on this measure.
“Emergency physicians and other health care providers battling on the front lines of the ongoing pandemic are already under unprecedented financial strain as they continue to bear the brunt of COVID-19,” Dr. Rosenberg said. “These cuts would have a devastating impact for the future of emergency medicine and could seriously impede patients’ access to emergency care when they need it most.”
“Long overdue”
But there also are champions for the approach CMS took in the E/M overhaul. The influential Medicare Payment Advisory Commission (MedPAC) has argued strongly for keeping the budget-neutral approach to the E/M overhaul.
In an Oct. 2 comment to CMS about the draft 2021 physician fee schedule, MedPAC Chairman Michael E. Chernew, PhD, said this approach would “help rebalance the fee schedule from services that have become overvalued to services that have become undervalued.”
This budget-neutral approach also “will go further in reducing the large gap in compensation between primary care physicians (who had a median income of $243,000 in 2018) and specialists such as surgeons (whose median income was $426,000 in 2018),” Dr. Chernew wrote.
In a Tuesday tweet, Robert B. Doherty, senior vice president of governmental affairs and public policy for the American College of Physicians, said CMS had “finalized long overdue payment increases for primary and comprehensive care including an add-in for more complex visits.”
The American Academy of Family Physicians joined ACP in a November 30 letter to congressional leaders, urging them to allow Medicare “to increase investment in primary care, benefiting millions of Medicare patients and the program itself, and reject last minute efforts to prevent these essential and long-overdue changes from going fully into effect on January 1, 2021.”
In the letter, AAFP and ACP and their cosigners argued for a need to address “underinvestment” in primary care by finalizing the E/M overhaul.
“Given that six in ten American adults have a chronic disease and four in ten have two or more chronic conditions, why would we, as a country, accept such an inadequate investment in the very care model that stands to provide maximum value to these patients?” they wrote. “Since we know that individuals with a longitudinal relationship with a primary care physician have better health outcomes and use fewer health care resources, why would we continue to direct money to higher-cost, marginal value services?”
A version of this article originally appeared on Medscape.com.
Medicare officials stuck with their plan to increase payments for office visits for primary care and several other specialties that focus on helping patients manage complex conditions such as diabetes. In doing so, Medicare also finalized cuts for other fields, triggering a new wave of protests.
The final version of the 2021 Medicare physician fee schedule was unveiled on the night of Dec. 1. The Centers for Medicare & Medicaid Services posted an unofficial copy of the rule, which will later be published in the Federal Register.
CMS said it completed work on this massive annual review of payments for clinicians later than it usually does because of the demands of the federal response to the COVID-19 pandemic. The 2021 physician fee rule will take effect within a 30-day period instead of the usual 60-day time frame.
The most contentious item proposed for 2021 was a reshuffling of payments among specialties as part of an overhaul of Medicare’s approach to valuing evaluation and management (E/M) services. There was broader support for other aspects of the E/M overhaul, which are intended to cut some of the administrative hassle clinicians face.
“This finalized policy marks the most significant updates to E/M codes in 30 years, reducing burden on doctors imposed by the coding system and rewarding time spent evaluating and managing their patients’ care,” CMS Administrator Seema Verma said in a statement. “In the past, the system has rewarded interventions and procedures over time spent with patients – time taken preventing disease and managing chronic illnesses.”
In the final rule, CMS summarized these results of the E/M changes in Table 106. CMS largely stuck with the approach outlined in a draft rule released in August, with minor changes in the amounts of cuts and increases.
Specialties in line for increases under the 2021 final physician fee schedule include allergy/immunology (9%), endocrinology (16%), family practice (13%), general practice (7%), geriatrics (3%), hematology/oncology (14%), internal medicine (4%), nephrology (6%), physician assistants (8%), psychiatry (7%), rheumatology (15%), and urology (8%).
In line for cuts would be anesthesiology (–8%), cardiac surgery (–8%), emergency medicine (–6%), general surgery (–6%), infectious disease (–4%), neurosurgery (–6%), physical/occupational therapy (–9%), plastic surgery (–7%), radiology (–10%), and thoracic surgery (–8%).
CMS had initially set these changes in 2021 pay in motion in the 2020 physician fee schedule. The agency subsequently faced significant opposition to its plans. Many physician groups sought to waive a “budget-neutral” approach to the E/M overhaul, which makes the offsetting of cuts necessary. They argued this would allow increased compensation for clinicians whose practices focus on office visits without requiring offsetting cuts from other fields of medicine.
The American Medical Association is among those urging Congress to prevent or postpone the payment reductions resulting from Medicare’s budget neutrality requirement as applied to the E/M overhaul.
In a Tuesday statement, AMA President Susan R. Bailey, MD, noted that many physicians are facing “substantial economic hardships due to COVID-19.”
By AMA’s calculations, CMS’ planned 2021 E/M overhaul could result in “a shocking reduction of 10.2% to Medicare payment rates,” according to Bailey’s statement. The AMA strongly supports other aspects of the E/M changes CMS finalized, which Bailey said will result in “simpler and more flexible” coding and documentation.
The Surgical Care Coalition, which represents about a dozen medical specialty associations, is asking members of Congress to block the full implementation of the E/M overhaul.
In a Dec. 1 statement, the coalition urged the passage of a bill (HR 8702) that has been introduced in the House by a bipartisan duo of physicians, Rep. Ami Bera, MD (D-Calif.), and Rep. Larry Bucshon, MD (R-Ind.). Their bill would effectively block the cuts from going into effect on January 1, 2021. It would provide an additional Medicare payment for certain services in 2021 and 2022 if the otherwise applicable payment is less than it would have been in 2020.
The Medicare E/M overhaul “was a dangerous policy even before the pandemic, and enacting it during the worst health care crisis in a century is unconscionable. If Congress fails to act, it will further strain a health care system that’s already been pushed to the brink due to the COVID-19 pandemic and undermine patient care,” said John A. Wilson, MD, president of the American Association of Neurological Surgeons, in a statement.
Also backing the Bera-Bucshon bill is the American College of Emergency Physicians. In a statement on Tuesday, ACEP President Mark Rosenberg, DO, MBA, urged Congress to act on this measure.
“Emergency physicians and other health care providers battling on the front lines of the ongoing pandemic are already under unprecedented financial strain as they continue to bear the brunt of COVID-19,” Dr. Rosenberg said. “These cuts would have a devastating impact for the future of emergency medicine and could seriously impede patients’ access to emergency care when they need it most.”
“Long overdue”
But there also are champions for the approach CMS took in the E/M overhaul. The influential Medicare Payment Advisory Commission (MedPAC) has argued strongly for keeping the budget-neutral approach to the E/M overhaul.
In an Oct. 2 comment to CMS about the draft 2021 physician fee schedule, MedPAC Chairman Michael E. Chernew, PhD, said this approach would “help rebalance the fee schedule from services that have become overvalued to services that have become undervalued.”
This budget-neutral approach also “will go further in reducing the large gap in compensation between primary care physicians (who had a median income of $243,000 in 2018) and specialists such as surgeons (whose median income was $426,000 in 2018),” Dr. Chernew wrote.
In a Tuesday tweet, Robert B. Doherty, senior vice president of governmental affairs and public policy for the American College of Physicians, said CMS had “finalized long overdue payment increases for primary and comprehensive care including an add-in for more complex visits.”
The American Academy of Family Physicians joined ACP in a November 30 letter to congressional leaders, urging them to allow Medicare “to increase investment in primary care, benefiting millions of Medicare patients and the program itself, and reject last minute efforts to prevent these essential and long-overdue changes from going fully into effect on January 1, 2021.”
In the letter, AAFP and ACP and their cosigners argued for a need to address “underinvestment” in primary care by finalizing the E/M overhaul.
“Given that six in ten American adults have a chronic disease and four in ten have two or more chronic conditions, why would we, as a country, accept such an inadequate investment in the very care model that stands to provide maximum value to these patients?” they wrote. “Since we know that individuals with a longitudinal relationship with a primary care physician have better health outcomes and use fewer health care resources, why would we continue to direct money to higher-cost, marginal value services?”
A version of this article originally appeared on Medscape.com.
Medicare officials stuck with their plan to increase payments for office visits for primary care and several other specialties that focus on helping patients manage complex conditions such as diabetes. In doing so, Medicare also finalized cuts for other fields, triggering a new wave of protests.
The final version of the 2021 Medicare physician fee schedule was unveiled on the night of Dec. 1. The Centers for Medicare & Medicaid Services posted an unofficial copy of the rule, which will later be published in the Federal Register.
CMS said it completed work on this massive annual review of payments for clinicians later than it usually does because of the demands of the federal response to the COVID-19 pandemic. The 2021 physician fee rule will take effect within a 30-day period instead of the usual 60-day time frame.
The most contentious item proposed for 2021 was a reshuffling of payments among specialties as part of an overhaul of Medicare’s approach to valuing evaluation and management (E/M) services. There was broader support for other aspects of the E/M overhaul, which are intended to cut some of the administrative hassle clinicians face.
“This finalized policy marks the most significant updates to E/M codes in 30 years, reducing burden on doctors imposed by the coding system and rewarding time spent evaluating and managing their patients’ care,” CMS Administrator Seema Verma said in a statement. “In the past, the system has rewarded interventions and procedures over time spent with patients – time taken preventing disease and managing chronic illnesses.”
In the final rule, CMS summarized these results of the E/M changes in Table 106. CMS largely stuck with the approach outlined in a draft rule released in August, with minor changes in the amounts of cuts and increases.
Specialties in line for increases under the 2021 final physician fee schedule include allergy/immunology (9%), endocrinology (16%), family practice (13%), general practice (7%), geriatrics (3%), hematology/oncology (14%), internal medicine (4%), nephrology (6%), physician assistants (8%), psychiatry (7%), rheumatology (15%), and urology (8%).
In line for cuts would be anesthesiology (–8%), cardiac surgery (–8%), emergency medicine (–6%), general surgery (–6%), infectious disease (–4%), neurosurgery (–6%), physical/occupational therapy (–9%), plastic surgery (–7%), radiology (–10%), and thoracic surgery (–8%).
CMS had initially set these changes in 2021 pay in motion in the 2020 physician fee schedule. The agency subsequently faced significant opposition to its plans. Many physician groups sought to waive a “budget-neutral” approach to the E/M overhaul, which makes the offsetting of cuts necessary. They argued this would allow increased compensation for clinicians whose practices focus on office visits without requiring offsetting cuts from other fields of medicine.
The American Medical Association is among those urging Congress to prevent or postpone the payment reductions resulting from Medicare’s budget neutrality requirement as applied to the E/M overhaul.
In a Tuesday statement, AMA President Susan R. Bailey, MD, noted that many physicians are facing “substantial economic hardships due to COVID-19.”
By AMA’s calculations, CMS’ planned 2021 E/M overhaul could result in “a shocking reduction of 10.2% to Medicare payment rates,” according to Bailey’s statement. The AMA strongly supports other aspects of the E/M changes CMS finalized, which Bailey said will result in “simpler and more flexible” coding and documentation.
The Surgical Care Coalition, which represents about a dozen medical specialty associations, is asking members of Congress to block the full implementation of the E/M overhaul.
In a Dec. 1 statement, the coalition urged the passage of a bill (HR 8702) that has been introduced in the House by a bipartisan duo of physicians, Rep. Ami Bera, MD (D-Calif.), and Rep. Larry Bucshon, MD (R-Ind.). Their bill would effectively block the cuts from going into effect on January 1, 2021. It would provide an additional Medicare payment for certain services in 2021 and 2022 if the otherwise applicable payment is less than it would have been in 2020.
The Medicare E/M overhaul “was a dangerous policy even before the pandemic, and enacting it during the worst health care crisis in a century is unconscionable. If Congress fails to act, it will further strain a health care system that’s already been pushed to the brink due to the COVID-19 pandemic and undermine patient care,” said John A. Wilson, MD, president of the American Association of Neurological Surgeons, in a statement.
Also backing the Bera-Bucshon bill is the American College of Emergency Physicians. In a statement on Tuesday, ACEP President Mark Rosenberg, DO, MBA, urged Congress to act on this measure.
“Emergency physicians and other health care providers battling on the front lines of the ongoing pandemic are already under unprecedented financial strain as they continue to bear the brunt of COVID-19,” Dr. Rosenberg said. “These cuts would have a devastating impact for the future of emergency medicine and could seriously impede patients’ access to emergency care when they need it most.”
“Long overdue”
But there also are champions for the approach CMS took in the E/M overhaul. The influential Medicare Payment Advisory Commission (MedPAC) has argued strongly for keeping the budget-neutral approach to the E/M overhaul.
In an Oct. 2 comment to CMS about the draft 2021 physician fee schedule, MedPAC Chairman Michael E. Chernew, PhD, said this approach would “help rebalance the fee schedule from services that have become overvalued to services that have become undervalued.”
This budget-neutral approach also “will go further in reducing the large gap in compensation between primary care physicians (who had a median income of $243,000 in 2018) and specialists such as surgeons (whose median income was $426,000 in 2018),” Dr. Chernew wrote.
In a Tuesday tweet, Robert B. Doherty, senior vice president of governmental affairs and public policy for the American College of Physicians, said CMS had “finalized long overdue payment increases for primary and comprehensive care including an add-in for more complex visits.”
The American Academy of Family Physicians joined ACP in a November 30 letter to congressional leaders, urging them to allow Medicare “to increase investment in primary care, benefiting millions of Medicare patients and the program itself, and reject last minute efforts to prevent these essential and long-overdue changes from going fully into effect on January 1, 2021.”
In the letter, AAFP and ACP and their cosigners argued for a need to address “underinvestment” in primary care by finalizing the E/M overhaul.
“Given that six in ten American adults have a chronic disease and four in ten have two or more chronic conditions, why would we, as a country, accept such an inadequate investment in the very care model that stands to provide maximum value to these patients?” they wrote. “Since we know that individuals with a longitudinal relationship with a primary care physician have better health outcomes and use fewer health care resources, why would we continue to direct money to higher-cost, marginal value services?”
A version of this article originally appeared on Medscape.com.