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Sharon Worcester is an award-winning medical journalist for MDedge News. She has been with the company since 1996, first as the Southeast Bureau Chief (1996-2009) when the company was known as International Medical News Group, then as a freelance writer (2010-2015) before returning as a reporter in 2015. She previously worked as a daily newspaper reporter covering health and local government. Sharon currently reports primarily on oncology and hematology. She has a BA from Eckerd College and an MA in Mass Communication/Print Journalism from the University of Florida. Connect with her via LinkedIn and follow her on twitter @SW_MedReporter.
FDA expands pembrolizumab approval for advanced melanoma
The over age 12 years. The FDA also extended the approval to those with stage III disease.
The FDA approval on Dec. 3 was based on first interim findings from the randomized, placebo-controlled KEYNOTE-716 trial, which evaluated patients with stage IIB and IIC disease.
Since the anti-PD-1 therapy was approved in metastatic melanoma 7 years ago, “we have built on this foundation in melanoma and have expanded the use of KEYTRUDA into earlier stages of this disease,” said Scot Ebbinghaus, MD, vice president, clinical research, Merck Research Laboratories, in a press release. “With today’s approval, we can now offer health care providers and patients 12 years and older the opportunity to help prevent melanoma recurrence with Keytruda across resected stage IIB, stage IIC, and stage III melanoma.”
In KEYNOTE-716, patients with completely resected stage IIB or IIC melanoma were randomly assigned to receive 200 mg of intravenous pembrolizumab, the pediatric dose 2 mg/kg (up to a maximum of 200 mg) every 3 weeks, or placebo for up to 1 year until disease recurrence or unacceptable toxicity.
After a median follow-up of 14.4 months, investigators reported a statistically significant 35% improvement in recurrence-free survival (RFS) in those treated with pembrolizumab, compared with those who received placebo (hazard ratio, 0.65).
The most common adverse reactions reported in patients receiving pembrolizumab in KEYNOTE-716 were fatigue, diarrhea, pruritus, and arthralgia, each occurring in at least 20% of patients.
“Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda,” according to Merck.
A version of this article first appeared on Medscape.com.
The over age 12 years. The FDA also extended the approval to those with stage III disease.
The FDA approval on Dec. 3 was based on first interim findings from the randomized, placebo-controlled KEYNOTE-716 trial, which evaluated patients with stage IIB and IIC disease.
Since the anti-PD-1 therapy was approved in metastatic melanoma 7 years ago, “we have built on this foundation in melanoma and have expanded the use of KEYTRUDA into earlier stages of this disease,” said Scot Ebbinghaus, MD, vice president, clinical research, Merck Research Laboratories, in a press release. “With today’s approval, we can now offer health care providers and patients 12 years and older the opportunity to help prevent melanoma recurrence with Keytruda across resected stage IIB, stage IIC, and stage III melanoma.”
In KEYNOTE-716, patients with completely resected stage IIB or IIC melanoma were randomly assigned to receive 200 mg of intravenous pembrolizumab, the pediatric dose 2 mg/kg (up to a maximum of 200 mg) every 3 weeks, or placebo for up to 1 year until disease recurrence or unacceptable toxicity.
After a median follow-up of 14.4 months, investigators reported a statistically significant 35% improvement in recurrence-free survival (RFS) in those treated with pembrolizumab, compared with those who received placebo (hazard ratio, 0.65).
The most common adverse reactions reported in patients receiving pembrolizumab in KEYNOTE-716 were fatigue, diarrhea, pruritus, and arthralgia, each occurring in at least 20% of patients.
“Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda,” according to Merck.
A version of this article first appeared on Medscape.com.
The over age 12 years. The FDA also extended the approval to those with stage III disease.
The FDA approval on Dec. 3 was based on first interim findings from the randomized, placebo-controlled KEYNOTE-716 trial, which evaluated patients with stage IIB and IIC disease.
Since the anti-PD-1 therapy was approved in metastatic melanoma 7 years ago, “we have built on this foundation in melanoma and have expanded the use of KEYTRUDA into earlier stages of this disease,” said Scot Ebbinghaus, MD, vice president, clinical research, Merck Research Laboratories, in a press release. “With today’s approval, we can now offer health care providers and patients 12 years and older the opportunity to help prevent melanoma recurrence with Keytruda across resected stage IIB, stage IIC, and stage III melanoma.”
In KEYNOTE-716, patients with completely resected stage IIB or IIC melanoma were randomly assigned to receive 200 mg of intravenous pembrolizumab, the pediatric dose 2 mg/kg (up to a maximum of 200 mg) every 3 weeks, or placebo for up to 1 year until disease recurrence or unacceptable toxicity.
After a median follow-up of 14.4 months, investigators reported a statistically significant 35% improvement in recurrence-free survival (RFS) in those treated with pembrolizumab, compared with those who received placebo (hazard ratio, 0.65).
The most common adverse reactions reported in patients receiving pembrolizumab in KEYNOTE-716 were fatigue, diarrhea, pruritus, and arthralgia, each occurring in at least 20% of patients.
“Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda,” according to Merck.
A version of this article first appeared on Medscape.com.
CLL and COVID-19: Outcome trends and lessons learned
Retrospective but the data also highlight areas for further investigation, according to the researchers.
Specifically, “the data highlight opportunities for further investigation into optimal management of COVID-19, immune response after infection, and effective vaccination strategy for patients with CLL,” Lindsey E. Roeker, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, New York, and colleagues wrote in a Nov. 4, 2021, letter to the editor of Blood.
The researchers noted that recently reported COVID-19 case fatality rates from two large series of patients with CLL ranged from 31% to 33%, but trends over time were unclear.
“To understand change in outcomes over time, we present this follow-up study, which builds upon a previously reported cohort with extended follow up and addition of more recently diagnosed cases,” they wrote, explaining that “early data from a small series suggest that patients with CLL may not consistently generate anti–SARS-CoV-2 antibodies after infection.”
“This finding, along with previous reports of inadequate response to vaccines in patients with CLL, highlight significant questions regarding COVID-19 vaccine efficacy in this population,” they added.
Trends in outcomes
The review of outcomes in 374 CLL patients from 45 centers who were diagnosed with COVID-19 between Feb. 17, 2020, and Feb. 1, 2021, showed an overall case fatality rate (CFR) of 28%. Among the 278 patients (75%) admitted to the hospital, the CFR was 36%; among those not admitted, the CFR was 4.3%.
Independent predictors of poor survival were ages over 75 years (adjusted hazard ratio, 1.6) and Cumulative Illness Rating Scale–Geriatric (CIRS) scores greater than 6 (aHR, 1.6).
Updated data for 254 patients diagnosed from Feb. 17 to April 30, 2020, and 120 diagnosed from May 1, 2020, to Feb. 1, 2021, showed that more patients in the early versus later cohort were admitted to the hospital (85% vs. 55%) and more required ICU admission (32% vs. 11%).
The overall case fatality rates in the early and later cohorts were 35% and 11%, respectively (P < .001), and among those requiring hospitalization, the rates were 40% and 20% (P = .003).
“The proportion of hospitalized patients requiring ICU-level care was lower in the later cohort (37% vs. 29%), whereas the CFR remained high for the subset of patients who required ICU-level care (52% vs. 50%; P = .89),” the investigators wrote, noting that “[a] difference in management of BTKi[Bruton’s tyrosine kinase inhibitor]-treated patients was observed in the early versus the later cohort.”
“In the early cohort, 76% of patients receiving BTKi had their drug therapy suspended or discontinued. In the later cohort, only 20% of BTKi-treated patients had their therapy suspended or discontinued,” they added.
Univariate analyses showed significant associations between use of remdesivir and OS (HR, 0.48) and use of convalescent plasma and OS (HR, 0.50) in patients who were admitted, whereas admitted patients who received corticosteroids or hydroxychloroquine had an increased risk of death (HRs, 1.73 and 1.53, respectively).
“Corticosteroids were associated with increased risk of death when the data were adjusted for admission status (HR, 1.8) and the need for mechanical ventilation (HR, 2.0), although they were not significantly associated with survival when the data were adjusted for use of supplemental oxygen (HR, 1.4),” they wrote, also noting that admitted patients treated with corticosteroids in the later cohort did not experience an OS benefit (HR, 2.6).
The findings mirror population-based studies with decreasing CFR (35% in those diagnosed before May 1, 2020, versus 11% in those diagnosed after that date), they said, adding that “these trends suggest that patients in the later cohort experienced a less severe clinical course and that the observed difference in CFR over time may not just be due to more frequent testing and identification of less symptomatic patients.”
Of note, the outcomes observed for steroid-treated patients in the current cohort contrast with those from the RECOVERY trial as published in July 2020, which “may be an artifact of their use in patients with more severe disease,” they suggested.
They added that these data “are hypothesis generating and suggest that COVID-19 directed interventions, particularly immunomodulatory agents, require prospective study, specifically in immunocompromised populations.”
The investigators also noted that, consistent with a prior single-center study, 60% of patients with CLL developed positive anti–SARS-CoV-2 serology results after polymerase chain reaction diagnosis of COVID-19, adding further evidence of nonuniform antibody production after COVID-19 in patients with CLL.
Study is ongoing to gain understanding of the immune response to SARS-CoV-2 vaccination in patients with CLL, they said.
Changing the odds
In a related commentary also published in Blood, Yair Herishanu, MD, and Chava Perry, MD, PhD, of Tel Aviv Sourasky Medical Center called the reduction in mortality over time as reported by Dr. Roeker and colleagues “encouraging and intriguing.”
“One explanation is that the later cohort included a larger proportion of patients with mild symptoms who were diagnosed because of increased awareness of COVID-19 and more extensive screening to detect SARS-CoV-2 over time. That is supported by the lower hospitalization rates and lower rates of hospitalized patients requiring ICU care in the later cohort,” they wrote. “Another possibility is better patient management owing to increasing experience, expanding therapeutic options, and improved capacity of health systems to manage an influx of patients.”
The lower mortality in hospitalized patients over time may reflect better management of patients over time, but it also highlights the significance of “early introduction of various anti–COVID-19 therapies to prevent clinical deterioration to ICU-level care,” they added.
Also intriguing, according to Dr. Herishanu and Dr. Perry, was the finding of increased secondary infections and death rates among corticosteroid-treatment patients.
In the RECOVERY trial, the use of dexamethasone improved survival in patients hospitalized with COVID-19 who received respiratory support. Perhaps the impaired immune reactions in patients with CLL moderate the hyperinflammatory reactions to COVID-19, thus turning corticosteroids beneficial effects to somewhat redundant in this frail population,” they wrote.
Further, the finding that only 60% of patients with CLL seroconvert after the acute phase of SARS-CoV-2 infection suggests CLL patients may be at risk for reinfection, which “justifies vaccinating all patients with CLL who have recovered from COVID-19.”
“Likewise, patients with CLL may develop persistent COVID-19 infection,” they added, explaining that “prolonged shedding of infectious SARS-CoV-2 virus and within-host genomic evolution may eventually lead to emergence of new virus variants.”
Given the high risk of severe COVID-19 disease and impaired antibody-mediated immune response to the virus and its vaccine, a booster dose may be warranted in patients with CLL who fail to achieve seropositivity after 2 vaccine doses, they said.
The available data to date “call for early application of antiviral drugs, [monoclonal antibodies], and convalescent plasma as well as improved vaccination strategy, to improve the odds for patients with CLL confronting COVID-19,” they concluded, adding that large-scale prospective studies on the clinical disease course, outcomes, efficacy of treatments, and vaccination timing and schedule in patients with CLL and COVID-19 are still warranted.
The research was supported by a National Cancer Institute Cancer Center support grant. Dr. Roeker, Dr. Herishanu, and Dr. Perry reported having no financial disclosures.
Retrospective but the data also highlight areas for further investigation, according to the researchers.
Specifically, “the data highlight opportunities for further investigation into optimal management of COVID-19, immune response after infection, and effective vaccination strategy for patients with CLL,” Lindsey E. Roeker, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, New York, and colleagues wrote in a Nov. 4, 2021, letter to the editor of Blood.
The researchers noted that recently reported COVID-19 case fatality rates from two large series of patients with CLL ranged from 31% to 33%, but trends over time were unclear.
“To understand change in outcomes over time, we present this follow-up study, which builds upon a previously reported cohort with extended follow up and addition of more recently diagnosed cases,” they wrote, explaining that “early data from a small series suggest that patients with CLL may not consistently generate anti–SARS-CoV-2 antibodies after infection.”
“This finding, along with previous reports of inadequate response to vaccines in patients with CLL, highlight significant questions regarding COVID-19 vaccine efficacy in this population,” they added.
Trends in outcomes
The review of outcomes in 374 CLL patients from 45 centers who were diagnosed with COVID-19 between Feb. 17, 2020, and Feb. 1, 2021, showed an overall case fatality rate (CFR) of 28%. Among the 278 patients (75%) admitted to the hospital, the CFR was 36%; among those not admitted, the CFR was 4.3%.
Independent predictors of poor survival were ages over 75 years (adjusted hazard ratio, 1.6) and Cumulative Illness Rating Scale–Geriatric (CIRS) scores greater than 6 (aHR, 1.6).
Updated data for 254 patients diagnosed from Feb. 17 to April 30, 2020, and 120 diagnosed from May 1, 2020, to Feb. 1, 2021, showed that more patients in the early versus later cohort were admitted to the hospital (85% vs. 55%) and more required ICU admission (32% vs. 11%).
The overall case fatality rates in the early and later cohorts were 35% and 11%, respectively (P < .001), and among those requiring hospitalization, the rates were 40% and 20% (P = .003).
“The proportion of hospitalized patients requiring ICU-level care was lower in the later cohort (37% vs. 29%), whereas the CFR remained high for the subset of patients who required ICU-level care (52% vs. 50%; P = .89),” the investigators wrote, noting that “[a] difference in management of BTKi[Bruton’s tyrosine kinase inhibitor]-treated patients was observed in the early versus the later cohort.”
“In the early cohort, 76% of patients receiving BTKi had their drug therapy suspended or discontinued. In the later cohort, only 20% of BTKi-treated patients had their therapy suspended or discontinued,” they added.
Univariate analyses showed significant associations between use of remdesivir and OS (HR, 0.48) and use of convalescent plasma and OS (HR, 0.50) in patients who were admitted, whereas admitted patients who received corticosteroids or hydroxychloroquine had an increased risk of death (HRs, 1.73 and 1.53, respectively).
“Corticosteroids were associated with increased risk of death when the data were adjusted for admission status (HR, 1.8) and the need for mechanical ventilation (HR, 2.0), although they were not significantly associated with survival when the data were adjusted for use of supplemental oxygen (HR, 1.4),” they wrote, also noting that admitted patients treated with corticosteroids in the later cohort did not experience an OS benefit (HR, 2.6).
The findings mirror population-based studies with decreasing CFR (35% in those diagnosed before May 1, 2020, versus 11% in those diagnosed after that date), they said, adding that “these trends suggest that patients in the later cohort experienced a less severe clinical course and that the observed difference in CFR over time may not just be due to more frequent testing and identification of less symptomatic patients.”
Of note, the outcomes observed for steroid-treated patients in the current cohort contrast with those from the RECOVERY trial as published in July 2020, which “may be an artifact of their use in patients with more severe disease,” they suggested.
They added that these data “are hypothesis generating and suggest that COVID-19 directed interventions, particularly immunomodulatory agents, require prospective study, specifically in immunocompromised populations.”
The investigators also noted that, consistent with a prior single-center study, 60% of patients with CLL developed positive anti–SARS-CoV-2 serology results after polymerase chain reaction diagnosis of COVID-19, adding further evidence of nonuniform antibody production after COVID-19 in patients with CLL.
Study is ongoing to gain understanding of the immune response to SARS-CoV-2 vaccination in patients with CLL, they said.
Changing the odds
In a related commentary also published in Blood, Yair Herishanu, MD, and Chava Perry, MD, PhD, of Tel Aviv Sourasky Medical Center called the reduction in mortality over time as reported by Dr. Roeker and colleagues “encouraging and intriguing.”
“One explanation is that the later cohort included a larger proportion of patients with mild symptoms who were diagnosed because of increased awareness of COVID-19 and more extensive screening to detect SARS-CoV-2 over time. That is supported by the lower hospitalization rates and lower rates of hospitalized patients requiring ICU care in the later cohort,” they wrote. “Another possibility is better patient management owing to increasing experience, expanding therapeutic options, and improved capacity of health systems to manage an influx of patients.”
The lower mortality in hospitalized patients over time may reflect better management of patients over time, but it also highlights the significance of “early introduction of various anti–COVID-19 therapies to prevent clinical deterioration to ICU-level care,” they added.
Also intriguing, according to Dr. Herishanu and Dr. Perry, was the finding of increased secondary infections and death rates among corticosteroid-treatment patients.
In the RECOVERY trial, the use of dexamethasone improved survival in patients hospitalized with COVID-19 who received respiratory support. Perhaps the impaired immune reactions in patients with CLL moderate the hyperinflammatory reactions to COVID-19, thus turning corticosteroids beneficial effects to somewhat redundant in this frail population,” they wrote.
Further, the finding that only 60% of patients with CLL seroconvert after the acute phase of SARS-CoV-2 infection suggests CLL patients may be at risk for reinfection, which “justifies vaccinating all patients with CLL who have recovered from COVID-19.”
“Likewise, patients with CLL may develop persistent COVID-19 infection,” they added, explaining that “prolonged shedding of infectious SARS-CoV-2 virus and within-host genomic evolution may eventually lead to emergence of new virus variants.”
Given the high risk of severe COVID-19 disease and impaired antibody-mediated immune response to the virus and its vaccine, a booster dose may be warranted in patients with CLL who fail to achieve seropositivity after 2 vaccine doses, they said.
The available data to date “call for early application of antiviral drugs, [monoclonal antibodies], and convalescent plasma as well as improved vaccination strategy, to improve the odds for patients with CLL confronting COVID-19,” they concluded, adding that large-scale prospective studies on the clinical disease course, outcomes, efficacy of treatments, and vaccination timing and schedule in patients with CLL and COVID-19 are still warranted.
The research was supported by a National Cancer Institute Cancer Center support grant. Dr. Roeker, Dr. Herishanu, and Dr. Perry reported having no financial disclosures.
Retrospective but the data also highlight areas for further investigation, according to the researchers.
Specifically, “the data highlight opportunities for further investigation into optimal management of COVID-19, immune response after infection, and effective vaccination strategy for patients with CLL,” Lindsey E. Roeker, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, New York, and colleagues wrote in a Nov. 4, 2021, letter to the editor of Blood.
The researchers noted that recently reported COVID-19 case fatality rates from two large series of patients with CLL ranged from 31% to 33%, but trends over time were unclear.
“To understand change in outcomes over time, we present this follow-up study, which builds upon a previously reported cohort with extended follow up and addition of more recently diagnosed cases,” they wrote, explaining that “early data from a small series suggest that patients with CLL may not consistently generate anti–SARS-CoV-2 antibodies after infection.”
“This finding, along with previous reports of inadequate response to vaccines in patients with CLL, highlight significant questions regarding COVID-19 vaccine efficacy in this population,” they added.
Trends in outcomes
The review of outcomes in 374 CLL patients from 45 centers who were diagnosed with COVID-19 between Feb. 17, 2020, and Feb. 1, 2021, showed an overall case fatality rate (CFR) of 28%. Among the 278 patients (75%) admitted to the hospital, the CFR was 36%; among those not admitted, the CFR was 4.3%.
Independent predictors of poor survival were ages over 75 years (adjusted hazard ratio, 1.6) and Cumulative Illness Rating Scale–Geriatric (CIRS) scores greater than 6 (aHR, 1.6).
Updated data for 254 patients diagnosed from Feb. 17 to April 30, 2020, and 120 diagnosed from May 1, 2020, to Feb. 1, 2021, showed that more patients in the early versus later cohort were admitted to the hospital (85% vs. 55%) and more required ICU admission (32% vs. 11%).
The overall case fatality rates in the early and later cohorts were 35% and 11%, respectively (P < .001), and among those requiring hospitalization, the rates were 40% and 20% (P = .003).
“The proportion of hospitalized patients requiring ICU-level care was lower in the later cohort (37% vs. 29%), whereas the CFR remained high for the subset of patients who required ICU-level care (52% vs. 50%; P = .89),” the investigators wrote, noting that “[a] difference in management of BTKi[Bruton’s tyrosine kinase inhibitor]-treated patients was observed in the early versus the later cohort.”
“In the early cohort, 76% of patients receiving BTKi had their drug therapy suspended or discontinued. In the later cohort, only 20% of BTKi-treated patients had their therapy suspended or discontinued,” they added.
Univariate analyses showed significant associations between use of remdesivir and OS (HR, 0.48) and use of convalescent plasma and OS (HR, 0.50) in patients who were admitted, whereas admitted patients who received corticosteroids or hydroxychloroquine had an increased risk of death (HRs, 1.73 and 1.53, respectively).
“Corticosteroids were associated with increased risk of death when the data were adjusted for admission status (HR, 1.8) and the need for mechanical ventilation (HR, 2.0), although they were not significantly associated with survival when the data were adjusted for use of supplemental oxygen (HR, 1.4),” they wrote, also noting that admitted patients treated with corticosteroids in the later cohort did not experience an OS benefit (HR, 2.6).
The findings mirror population-based studies with decreasing CFR (35% in those diagnosed before May 1, 2020, versus 11% in those diagnosed after that date), they said, adding that “these trends suggest that patients in the later cohort experienced a less severe clinical course and that the observed difference in CFR over time may not just be due to more frequent testing and identification of less symptomatic patients.”
Of note, the outcomes observed for steroid-treated patients in the current cohort contrast with those from the RECOVERY trial as published in July 2020, which “may be an artifact of their use in patients with more severe disease,” they suggested.
They added that these data “are hypothesis generating and suggest that COVID-19 directed interventions, particularly immunomodulatory agents, require prospective study, specifically in immunocompromised populations.”
The investigators also noted that, consistent with a prior single-center study, 60% of patients with CLL developed positive anti–SARS-CoV-2 serology results after polymerase chain reaction diagnosis of COVID-19, adding further evidence of nonuniform antibody production after COVID-19 in patients with CLL.
Study is ongoing to gain understanding of the immune response to SARS-CoV-2 vaccination in patients with CLL, they said.
Changing the odds
In a related commentary also published in Blood, Yair Herishanu, MD, and Chava Perry, MD, PhD, of Tel Aviv Sourasky Medical Center called the reduction in mortality over time as reported by Dr. Roeker and colleagues “encouraging and intriguing.”
“One explanation is that the later cohort included a larger proportion of patients with mild symptoms who were diagnosed because of increased awareness of COVID-19 and more extensive screening to detect SARS-CoV-2 over time. That is supported by the lower hospitalization rates and lower rates of hospitalized patients requiring ICU care in the later cohort,” they wrote. “Another possibility is better patient management owing to increasing experience, expanding therapeutic options, and improved capacity of health systems to manage an influx of patients.”
The lower mortality in hospitalized patients over time may reflect better management of patients over time, but it also highlights the significance of “early introduction of various anti–COVID-19 therapies to prevent clinical deterioration to ICU-level care,” they added.
Also intriguing, according to Dr. Herishanu and Dr. Perry, was the finding of increased secondary infections and death rates among corticosteroid-treatment patients.
In the RECOVERY trial, the use of dexamethasone improved survival in patients hospitalized with COVID-19 who received respiratory support. Perhaps the impaired immune reactions in patients with CLL moderate the hyperinflammatory reactions to COVID-19, thus turning corticosteroids beneficial effects to somewhat redundant in this frail population,” they wrote.
Further, the finding that only 60% of patients with CLL seroconvert after the acute phase of SARS-CoV-2 infection suggests CLL patients may be at risk for reinfection, which “justifies vaccinating all patients with CLL who have recovered from COVID-19.”
“Likewise, patients with CLL may develop persistent COVID-19 infection,” they added, explaining that “prolonged shedding of infectious SARS-CoV-2 virus and within-host genomic evolution may eventually lead to emergence of new virus variants.”
Given the high risk of severe COVID-19 disease and impaired antibody-mediated immune response to the virus and its vaccine, a booster dose may be warranted in patients with CLL who fail to achieve seropositivity after 2 vaccine doses, they said.
The available data to date “call for early application of antiviral drugs, [monoclonal antibodies], and convalescent plasma as well as improved vaccination strategy, to improve the odds for patients with CLL confronting COVID-19,” they concluded, adding that large-scale prospective studies on the clinical disease course, outcomes, efficacy of treatments, and vaccination timing and schedule in patients with CLL and COVID-19 are still warranted.
The research was supported by a National Cancer Institute Cancer Center support grant. Dr. Roeker, Dr. Herishanu, and Dr. Perry reported having no financial disclosures.
FROM BLOOD
Differences in response to immunotherapy in men versus women
.
In a population-based cohort study, women with advanced melanoma and prior ipilimumab treatment who then received combination nivolumab and ipilimumab immunotherapy had a more than twofold increase in the risk for death in comparison with their male counterparts.
The hazard ratio (HR) for mortality among women versus men treated with the combination immunotherapy after prior ipilimumab treatment was 2.06 (P = .003). No such difference was observed among those receiving single-agent therapy with pembrolizumab or nivolumab (HR for mortality in women vs. men, 0.97; P = .85) or among patients without prior ipilimumab use (HR, 0.85; P = .16).
Women with prior ipilimumab use also had a nearly threefold increase in the risk for death with combination immunotherapy versus with single-agent anti–programmed cell death protein–1 (anti-PD-1) therapy (HR, 2.82), but no such difference was seen among the men in the study.
The findings were published online Dec. 2 in JAMA Network Open.
They come from an analysis of Surveillance, Epidemiology, and End Results (SEERS)–Medicare linked data for 982 men and 387 women with stage III or IV melanoma whose median age was 75 years.
The findings suggest that the patient’s sex should be considered in treatment planning to optimize outcomes, the authors noted.
“These novel findings suggest that, for women with a prior history of ipilimumab, treatment with anti-PD-1 therapy may be preferable to combination therapy, whereas for men, it is unclear which treatment is better,” they wrote.
In a press release, principal author Grace Lu-Yao, PhD, a professor at Thomas Jefferson University, Philadelphia, acknowledged that it remains unclear whether the increased risk for death in women is a result of treatment side effects or lack of efficacy, but she stressed that “this is a powerful signal in real-world data that we need to investigate further.
“This data is a wake-up call based on the experience of hundreds of patients on these drugs,” said Dr. Lu-Yao. “This real-world data demonstrates that the results derived from men might not be applicable to women and it is critical to design studies with sufficient power to evaluate treatment effectiveness by sex.”
Relevance for routine practice is unclear
The relevance of the findings for routine practice is unclear, given the median age of the cohort and a lack of data on whether excess mortality was cancer- or toxicity-related or due to another cause, Jeffrey S. Weber, MD, PhD, told this news organization. Dr. Weber is a professor and deputy director of the Laura and Isaac Perlmutter Cancer Center at New York University.
“The study is interesting and detailed, but it is a rather narrowly defined cohort that is over 65 and has a median of age 75, [which is] very different than most melanoma patient cohorts of patients treated with immunotherapy, whose median age is 10 years younger,” Dr. Weber said in an interview.
Furthermore, “in practice, almost no current patients will have been previously treated with ipilimumab and then receive combination immunotherapy,” he said. “Overall, these data would not impact on how I treat patients,” he said.
Gender differences in response
This study is not the first to show a gender-based difference in outcomes after immunotherapy. As previously reported by this news organization, a meta-analysis published in The Lancet Oncology in 2018 showed that immune checkpoint inhibitors are twice as effective as standard cancer therapies in men with advanced solid tumors, compared with their female counterparts.
However, sex-based differences remain under-assessed despite “accumulating evidence of the potential role played by sex in drug effectiveness owing to the biological differences between men and women,” wrote the authors of the latest study in melanoma.
“This lack of attention on the association of sex with the effectiveness of immune checkpoint inhibitor (ICI)–based immunotherapy may have significant negative consequences, especially because these treatments are associated with high toxicity and high treatment cost. For future trials, it would be crucial to examine effect modification by sex,” they added.
The study was funded by the Sidney Kimmel Cancer Center. Dr. Lu-Yao and coauthors have disclosed no relevant financial relationships. Dr. Weber is a regular contributor to Medscape. He reports relationships with Bristol-Myers Squibb, GlaxoSmithKline, Genentech BioOncology, Merck & Co, Novartis, EMD Serono, Celldex, CytomX, Nektar, Roche, Altor, Daiichi-Sankyo, and Eli Lilly and is named on patents filed for biomarkers for ipilimumab and nivolumab.
A version of this article first appeared on Medscape.com.
.
In a population-based cohort study, women with advanced melanoma and prior ipilimumab treatment who then received combination nivolumab and ipilimumab immunotherapy had a more than twofold increase in the risk for death in comparison with their male counterparts.
The hazard ratio (HR) for mortality among women versus men treated with the combination immunotherapy after prior ipilimumab treatment was 2.06 (P = .003). No such difference was observed among those receiving single-agent therapy with pembrolizumab or nivolumab (HR for mortality in women vs. men, 0.97; P = .85) or among patients without prior ipilimumab use (HR, 0.85; P = .16).
Women with prior ipilimumab use also had a nearly threefold increase in the risk for death with combination immunotherapy versus with single-agent anti–programmed cell death protein–1 (anti-PD-1) therapy (HR, 2.82), but no such difference was seen among the men in the study.
The findings were published online Dec. 2 in JAMA Network Open.
They come from an analysis of Surveillance, Epidemiology, and End Results (SEERS)–Medicare linked data for 982 men and 387 women with stage III or IV melanoma whose median age was 75 years.
The findings suggest that the patient’s sex should be considered in treatment planning to optimize outcomes, the authors noted.
“These novel findings suggest that, for women with a prior history of ipilimumab, treatment with anti-PD-1 therapy may be preferable to combination therapy, whereas for men, it is unclear which treatment is better,” they wrote.
In a press release, principal author Grace Lu-Yao, PhD, a professor at Thomas Jefferson University, Philadelphia, acknowledged that it remains unclear whether the increased risk for death in women is a result of treatment side effects or lack of efficacy, but she stressed that “this is a powerful signal in real-world data that we need to investigate further.
“This data is a wake-up call based on the experience of hundreds of patients on these drugs,” said Dr. Lu-Yao. “This real-world data demonstrates that the results derived from men might not be applicable to women and it is critical to design studies with sufficient power to evaluate treatment effectiveness by sex.”
Relevance for routine practice is unclear
The relevance of the findings for routine practice is unclear, given the median age of the cohort and a lack of data on whether excess mortality was cancer- or toxicity-related or due to another cause, Jeffrey S. Weber, MD, PhD, told this news organization. Dr. Weber is a professor and deputy director of the Laura and Isaac Perlmutter Cancer Center at New York University.
“The study is interesting and detailed, but it is a rather narrowly defined cohort that is over 65 and has a median of age 75, [which is] very different than most melanoma patient cohorts of patients treated with immunotherapy, whose median age is 10 years younger,” Dr. Weber said in an interview.
Furthermore, “in practice, almost no current patients will have been previously treated with ipilimumab and then receive combination immunotherapy,” he said. “Overall, these data would not impact on how I treat patients,” he said.
Gender differences in response
This study is not the first to show a gender-based difference in outcomes after immunotherapy. As previously reported by this news organization, a meta-analysis published in The Lancet Oncology in 2018 showed that immune checkpoint inhibitors are twice as effective as standard cancer therapies in men with advanced solid tumors, compared with their female counterparts.
However, sex-based differences remain under-assessed despite “accumulating evidence of the potential role played by sex in drug effectiveness owing to the biological differences between men and women,” wrote the authors of the latest study in melanoma.
“This lack of attention on the association of sex with the effectiveness of immune checkpoint inhibitor (ICI)–based immunotherapy may have significant negative consequences, especially because these treatments are associated with high toxicity and high treatment cost. For future trials, it would be crucial to examine effect modification by sex,” they added.
The study was funded by the Sidney Kimmel Cancer Center. Dr. Lu-Yao and coauthors have disclosed no relevant financial relationships. Dr. Weber is a regular contributor to Medscape. He reports relationships with Bristol-Myers Squibb, GlaxoSmithKline, Genentech BioOncology, Merck & Co, Novartis, EMD Serono, Celldex, CytomX, Nektar, Roche, Altor, Daiichi-Sankyo, and Eli Lilly and is named on patents filed for biomarkers for ipilimumab and nivolumab.
A version of this article first appeared on Medscape.com.
.
In a population-based cohort study, women with advanced melanoma and prior ipilimumab treatment who then received combination nivolumab and ipilimumab immunotherapy had a more than twofold increase in the risk for death in comparison with their male counterparts.
The hazard ratio (HR) for mortality among women versus men treated with the combination immunotherapy after prior ipilimumab treatment was 2.06 (P = .003). No such difference was observed among those receiving single-agent therapy with pembrolizumab or nivolumab (HR for mortality in women vs. men, 0.97; P = .85) or among patients without prior ipilimumab use (HR, 0.85; P = .16).
Women with prior ipilimumab use also had a nearly threefold increase in the risk for death with combination immunotherapy versus with single-agent anti–programmed cell death protein–1 (anti-PD-1) therapy (HR, 2.82), but no such difference was seen among the men in the study.
The findings were published online Dec. 2 in JAMA Network Open.
They come from an analysis of Surveillance, Epidemiology, and End Results (SEERS)–Medicare linked data for 982 men and 387 women with stage III or IV melanoma whose median age was 75 years.
The findings suggest that the patient’s sex should be considered in treatment planning to optimize outcomes, the authors noted.
“These novel findings suggest that, for women with a prior history of ipilimumab, treatment with anti-PD-1 therapy may be preferable to combination therapy, whereas for men, it is unclear which treatment is better,” they wrote.
In a press release, principal author Grace Lu-Yao, PhD, a professor at Thomas Jefferson University, Philadelphia, acknowledged that it remains unclear whether the increased risk for death in women is a result of treatment side effects or lack of efficacy, but she stressed that “this is a powerful signal in real-world data that we need to investigate further.
“This data is a wake-up call based on the experience of hundreds of patients on these drugs,” said Dr. Lu-Yao. “This real-world data demonstrates that the results derived from men might not be applicable to women and it is critical to design studies with sufficient power to evaluate treatment effectiveness by sex.”
Relevance for routine practice is unclear
The relevance of the findings for routine practice is unclear, given the median age of the cohort and a lack of data on whether excess mortality was cancer- or toxicity-related or due to another cause, Jeffrey S. Weber, MD, PhD, told this news organization. Dr. Weber is a professor and deputy director of the Laura and Isaac Perlmutter Cancer Center at New York University.
“The study is interesting and detailed, but it is a rather narrowly defined cohort that is over 65 and has a median of age 75, [which is] very different than most melanoma patient cohorts of patients treated with immunotherapy, whose median age is 10 years younger,” Dr. Weber said in an interview.
Furthermore, “in practice, almost no current patients will have been previously treated with ipilimumab and then receive combination immunotherapy,” he said. “Overall, these data would not impact on how I treat patients,” he said.
Gender differences in response
This study is not the first to show a gender-based difference in outcomes after immunotherapy. As previously reported by this news organization, a meta-analysis published in The Lancet Oncology in 2018 showed that immune checkpoint inhibitors are twice as effective as standard cancer therapies in men with advanced solid tumors, compared with their female counterparts.
However, sex-based differences remain under-assessed despite “accumulating evidence of the potential role played by sex in drug effectiveness owing to the biological differences between men and women,” wrote the authors of the latest study in melanoma.
“This lack of attention on the association of sex with the effectiveness of immune checkpoint inhibitor (ICI)–based immunotherapy may have significant negative consequences, especially because these treatments are associated with high toxicity and high treatment cost. For future trials, it would be crucial to examine effect modification by sex,” they added.
The study was funded by the Sidney Kimmel Cancer Center. Dr. Lu-Yao and coauthors have disclosed no relevant financial relationships. Dr. Weber is a regular contributor to Medscape. He reports relationships with Bristol-Myers Squibb, GlaxoSmithKline, Genentech BioOncology, Merck & Co, Novartis, EMD Serono, Celldex, CytomX, Nektar, Roche, Altor, Daiichi-Sankyo, and Eli Lilly and is named on patents filed for biomarkers for ipilimumab and nivolumab.
A version of this article first appeared on Medscape.com.
Single-dose HPV vaccination highly effective
A single dose of human papillomavirus (HPV) vaccine was highly effective at preventing oncogenic infection, rivaling the protection offered by multidose regimens, according to results from the KEN SHE trial, based in Kenya.
The findings, published on the preprint server Research Square and presented Nov. 17 at the 34th International Papillomavirus Conference in Toronto, bring “renewed energy to the push to make cervical cancer the first cancer to be wiped out globally,” according to co–principal investigator Ruanne V. Barnabas, PhD, a professor of global health at the University of Washington, Seattle.
Decision-makers will consider these findings, which have not yet been peer-reviewed, along with other evidence to determine if dosing-schedule changes are warranted, she told this news organization.
In a press release, Samuel Kariuki, PhD, acting director general, Kenya Medical Research Institute, who was not involved in the research, called the findings a “game changer” that could “substantially reduce the incidence of HPV-attributable cervical cancer.”
Between 2018 and 2019, Dr. Barnabas and her colleagues enrolled 2,275 sexually active, HPV-vaccine–naive women in Kenya in their study. The women, 15-20 years of age, were randomly assigned to receive a bivalent vaccine (HPV 16/18), a nonavalent vaccine (HPV 16/18/31/33/45/52/58/6/11), or a vaccine against meningococcal meningitis.
Most participants (57%) were between 15 and 17 years of age, and 61% reported one lifetime sexual partner. The women underwent genital and cervical swabs at enrollment to test for HPV DNA and had blood drawn to test for antibodies. During 18 months of follow-up, they had cervical swabs every 6 months and a vaginal swab at 3 months to test for HPV DNA.
The researchers detected 38 persistent HPV 16/18 infections in women who had tested negative for HPV 16/18 antibodies at enrollment and for HPV 16/18 DNA at enrollment and month 3 – one in each of the HPV-vaccine groups and 36 in the meningococcal group. This infection rate corresponded to a vaccine efficacy of 97.5% (P < .001) against HPV 16/18 for both the bivalent and nonavalent vaccines, which is “comparable to that seen in multidose vaccine trials,” the researchers write.
Among women negative for HPV 16/18/31/33/45/52/58 at the beginning of the trial, 33 had persistent infections: four in the nonavalent vaccine group and 29 in the meningococcal group, demonstrating an efficacy of 89% (P < .001) against all seven oncogenic strains contained in the vaccine.
Even if women tested positive for one strain of HPV, the vaccine protected them from other strains of the virus, the investigators noted.
Serious adverse events occurred in 4.5%-5.2% of participants across the study arms.
The KEN SHE trial comes 15 years after the U.S. Food and Drug Administration approved the first HPV vaccine – Merck’s Gardasil. Two others, Cervarix and Gardasil-9, have since been approved, but cost and supply issues have inhibited coverage, particularly in areas where the cervical cancer burden is high, the researchers noted.
Recent data indicate that just 15% of girls globally are vaccinated against HPV, but a single-dose vaccine would “simplify logistics and decrease costs,” thereby improving the chances of reaching the World Health Organization goal of vaccinating 90% of 15-year-old girls against HPV by 2030, Dr. Barnabas said in a press release about the trial.
Co–principal investigator Nelly Mugo, MBChB, MPH, senior principal clinical research scientist with the Center for Clinical Research at the Kenya Medical Research Institute in Nairobi, further emphasized the importance of the findings, noting in the press release that the “trial brings new energy to the elimination of cervical cancer. It brings great hope to the women living in countries like Kenya, who have a high burden of the disease.”
Dr. Mugo is also an associate research professor of global health at the University of Washington, Seattle.
Dr. Barnabas said women have been given multiple doses of the HPV vaccine because of “gaps in evidence for the effectiveness of a single-dose vaccine and concerns about clinically meaningful differences in efficacy.
“Observational data suggested that the single-dose HPV vaccine could have good efficacy, but because the data were not from randomized trials, that could have been from chance,” she explained, noting, however, that “sufficient evidence supported the decrease in doses from three to two doses for girls 15 years of age and younger.”
Going forward, the researchers will conduct immunobridging studies to other populations and will continue follow-up to assess the durability of single-dose efficacy, Dr. Barnabas said.
“The results from the KEN SHE trial support the use of single-dose HPV vaccination to increase access and coverage,” she concluded.
The KEN SHE trial was funded by the Bill & Melinda Gates Foundation (BMGF). Dr. Barnabas reports grants from BMGF and grants from King K. Holmes Professorship in STDs and AIDS during the conduct of the study, and grants from BMGF, National Institutes of Health, and manuscript and abstract writing support from Regeneron Pharmaceuticals outside the submitted work.
A version of this article first appeared on Medscape.com.
A single dose of human papillomavirus (HPV) vaccine was highly effective at preventing oncogenic infection, rivaling the protection offered by multidose regimens, according to results from the KEN SHE trial, based in Kenya.
The findings, published on the preprint server Research Square and presented Nov. 17 at the 34th International Papillomavirus Conference in Toronto, bring “renewed energy to the push to make cervical cancer the first cancer to be wiped out globally,” according to co–principal investigator Ruanne V. Barnabas, PhD, a professor of global health at the University of Washington, Seattle.
Decision-makers will consider these findings, which have not yet been peer-reviewed, along with other evidence to determine if dosing-schedule changes are warranted, she told this news organization.
In a press release, Samuel Kariuki, PhD, acting director general, Kenya Medical Research Institute, who was not involved in the research, called the findings a “game changer” that could “substantially reduce the incidence of HPV-attributable cervical cancer.”
Between 2018 and 2019, Dr. Barnabas and her colleagues enrolled 2,275 sexually active, HPV-vaccine–naive women in Kenya in their study. The women, 15-20 years of age, were randomly assigned to receive a bivalent vaccine (HPV 16/18), a nonavalent vaccine (HPV 16/18/31/33/45/52/58/6/11), or a vaccine against meningococcal meningitis.
Most participants (57%) were between 15 and 17 years of age, and 61% reported one lifetime sexual partner. The women underwent genital and cervical swabs at enrollment to test for HPV DNA and had blood drawn to test for antibodies. During 18 months of follow-up, they had cervical swabs every 6 months and a vaginal swab at 3 months to test for HPV DNA.
The researchers detected 38 persistent HPV 16/18 infections in women who had tested negative for HPV 16/18 antibodies at enrollment and for HPV 16/18 DNA at enrollment and month 3 – one in each of the HPV-vaccine groups and 36 in the meningococcal group. This infection rate corresponded to a vaccine efficacy of 97.5% (P < .001) against HPV 16/18 for both the bivalent and nonavalent vaccines, which is “comparable to that seen in multidose vaccine trials,” the researchers write.
Among women negative for HPV 16/18/31/33/45/52/58 at the beginning of the trial, 33 had persistent infections: four in the nonavalent vaccine group and 29 in the meningococcal group, demonstrating an efficacy of 89% (P < .001) against all seven oncogenic strains contained in the vaccine.
Even if women tested positive for one strain of HPV, the vaccine protected them from other strains of the virus, the investigators noted.
Serious adverse events occurred in 4.5%-5.2% of participants across the study arms.
The KEN SHE trial comes 15 years after the U.S. Food and Drug Administration approved the first HPV vaccine – Merck’s Gardasil. Two others, Cervarix and Gardasil-9, have since been approved, but cost and supply issues have inhibited coverage, particularly in areas where the cervical cancer burden is high, the researchers noted.
Recent data indicate that just 15% of girls globally are vaccinated against HPV, but a single-dose vaccine would “simplify logistics and decrease costs,” thereby improving the chances of reaching the World Health Organization goal of vaccinating 90% of 15-year-old girls against HPV by 2030, Dr. Barnabas said in a press release about the trial.
Co–principal investigator Nelly Mugo, MBChB, MPH, senior principal clinical research scientist with the Center for Clinical Research at the Kenya Medical Research Institute in Nairobi, further emphasized the importance of the findings, noting in the press release that the “trial brings new energy to the elimination of cervical cancer. It brings great hope to the women living in countries like Kenya, who have a high burden of the disease.”
Dr. Mugo is also an associate research professor of global health at the University of Washington, Seattle.
Dr. Barnabas said women have been given multiple doses of the HPV vaccine because of “gaps in evidence for the effectiveness of a single-dose vaccine and concerns about clinically meaningful differences in efficacy.
“Observational data suggested that the single-dose HPV vaccine could have good efficacy, but because the data were not from randomized trials, that could have been from chance,” she explained, noting, however, that “sufficient evidence supported the decrease in doses from three to two doses for girls 15 years of age and younger.”
Going forward, the researchers will conduct immunobridging studies to other populations and will continue follow-up to assess the durability of single-dose efficacy, Dr. Barnabas said.
“The results from the KEN SHE trial support the use of single-dose HPV vaccination to increase access and coverage,” she concluded.
The KEN SHE trial was funded by the Bill & Melinda Gates Foundation (BMGF). Dr. Barnabas reports grants from BMGF and grants from King K. Holmes Professorship in STDs and AIDS during the conduct of the study, and grants from BMGF, National Institutes of Health, and manuscript and abstract writing support from Regeneron Pharmaceuticals outside the submitted work.
A version of this article first appeared on Medscape.com.
A single dose of human papillomavirus (HPV) vaccine was highly effective at preventing oncogenic infection, rivaling the protection offered by multidose regimens, according to results from the KEN SHE trial, based in Kenya.
The findings, published on the preprint server Research Square and presented Nov. 17 at the 34th International Papillomavirus Conference in Toronto, bring “renewed energy to the push to make cervical cancer the first cancer to be wiped out globally,” according to co–principal investigator Ruanne V. Barnabas, PhD, a professor of global health at the University of Washington, Seattle.
Decision-makers will consider these findings, which have not yet been peer-reviewed, along with other evidence to determine if dosing-schedule changes are warranted, she told this news organization.
In a press release, Samuel Kariuki, PhD, acting director general, Kenya Medical Research Institute, who was not involved in the research, called the findings a “game changer” that could “substantially reduce the incidence of HPV-attributable cervical cancer.”
Between 2018 and 2019, Dr. Barnabas and her colleagues enrolled 2,275 sexually active, HPV-vaccine–naive women in Kenya in their study. The women, 15-20 years of age, were randomly assigned to receive a bivalent vaccine (HPV 16/18), a nonavalent vaccine (HPV 16/18/31/33/45/52/58/6/11), or a vaccine against meningococcal meningitis.
Most participants (57%) were between 15 and 17 years of age, and 61% reported one lifetime sexual partner. The women underwent genital and cervical swabs at enrollment to test for HPV DNA and had blood drawn to test for antibodies. During 18 months of follow-up, they had cervical swabs every 6 months and a vaginal swab at 3 months to test for HPV DNA.
The researchers detected 38 persistent HPV 16/18 infections in women who had tested negative for HPV 16/18 antibodies at enrollment and for HPV 16/18 DNA at enrollment and month 3 – one in each of the HPV-vaccine groups and 36 in the meningococcal group. This infection rate corresponded to a vaccine efficacy of 97.5% (P < .001) against HPV 16/18 for both the bivalent and nonavalent vaccines, which is “comparable to that seen in multidose vaccine trials,” the researchers write.
Among women negative for HPV 16/18/31/33/45/52/58 at the beginning of the trial, 33 had persistent infections: four in the nonavalent vaccine group and 29 in the meningococcal group, demonstrating an efficacy of 89% (P < .001) against all seven oncogenic strains contained in the vaccine.
Even if women tested positive for one strain of HPV, the vaccine protected them from other strains of the virus, the investigators noted.
Serious adverse events occurred in 4.5%-5.2% of participants across the study arms.
The KEN SHE trial comes 15 years after the U.S. Food and Drug Administration approved the first HPV vaccine – Merck’s Gardasil. Two others, Cervarix and Gardasil-9, have since been approved, but cost and supply issues have inhibited coverage, particularly in areas where the cervical cancer burden is high, the researchers noted.
Recent data indicate that just 15% of girls globally are vaccinated against HPV, but a single-dose vaccine would “simplify logistics and decrease costs,” thereby improving the chances of reaching the World Health Organization goal of vaccinating 90% of 15-year-old girls against HPV by 2030, Dr. Barnabas said in a press release about the trial.
Co–principal investigator Nelly Mugo, MBChB, MPH, senior principal clinical research scientist with the Center for Clinical Research at the Kenya Medical Research Institute in Nairobi, further emphasized the importance of the findings, noting in the press release that the “trial brings new energy to the elimination of cervical cancer. It brings great hope to the women living in countries like Kenya, who have a high burden of the disease.”
Dr. Mugo is also an associate research professor of global health at the University of Washington, Seattle.
Dr. Barnabas said women have been given multiple doses of the HPV vaccine because of “gaps in evidence for the effectiveness of a single-dose vaccine and concerns about clinically meaningful differences in efficacy.
“Observational data suggested that the single-dose HPV vaccine could have good efficacy, but because the data were not from randomized trials, that could have been from chance,” she explained, noting, however, that “sufficient evidence supported the decrease in doses from three to two doses for girls 15 years of age and younger.”
Going forward, the researchers will conduct immunobridging studies to other populations and will continue follow-up to assess the durability of single-dose efficacy, Dr. Barnabas said.
“The results from the KEN SHE trial support the use of single-dose HPV vaccination to increase access and coverage,” she concluded.
The KEN SHE trial was funded by the Bill & Melinda Gates Foundation (BMGF). Dr. Barnabas reports grants from BMGF and grants from King K. Holmes Professorship in STDs and AIDS during the conduct of the study, and grants from BMGF, National Institutes of Health, and manuscript and abstract writing support from Regeneron Pharmaceuticals outside the submitted work.
A version of this article first appeared on Medscape.com.
Easing access to DLBCL treatments: Patient study reveals racial differences
, but other “multifaceted and personalized” strategies are also needed, a new study shows.
The findings, from a survey focused on patients’ willingness to travel for treatment, offer valuable insights on DLBCL patients’ perspectives and care needs, and on racial and sociodemographic variations among their perspectives and needs, the investigators said.
Treatment decision factors
They used a choice-based conjoint analysis to assess the relative value that 302 patients with DLBCL place on clinical factors, continuity of care, and travel time. Patients were asked to select treatment plans, choosing between pairs of hypothetical options that varied in travel time, follow-up arrangement, oncologist continuity, 2-year overall survival, and intensive care unit admission rate, the authors explained.
When all follow-up care in the hypothetical scenario was provided at the treatment center, plans requiring travel time of longer than 30 minutes were less attractive, Zachary A. K. Frosch, MD, and colleagues reported in the Journal of Clinical Oncology.
Importance weights, when compared with 30-minute travel time, were –0.54, –0.57, and –0.17 for 60, 90, and 120 minute travel time, they found.
However, scenarios involving shared follow-up by the treatment center and patients’ local providers mitigated the negative impact of travel on treatment plan choice, they noted (importance weights, 0.63, 0.32, and 0.26 at 60, 90, and 120-minute travel times).
Importantly, an analysis of responses based on sociodemographic factors showed that Black participants were less likely to choose plans requiring longer travel, regardless of follow-up arrangement, the authors said.
“Black patients were also less likely than White patients to choose treatment plans that offered lower continuity with their current oncologist (importance weights, 2.50 to vs. 1.09, respectively),” they wrote.
Further, when making choices that required trade-offs, treatment efficacy was a weaker driver of treatment plan preferences for Black patient than for White patients (importance weights, 0.34 vs. 0.75 per 5% point increase in overall survival, respectively).
Why the findings matter
“Certain cancer treatments aren’t offered everywhere. Examples of this are the bone marrow transplants and [chimeric antigen receptor T-cell] therapies used to treat patients with blood cancers such as lymphoma,” Dr. Frosch said in an interview, adding that the limited geographic availability of these treatments means that patients who need them may have to travel farther and also to establish care with a new oncologist.
“These are both things that some patients may be reluctant to do,” added Dr. Frosch, who was with the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, at the time of the study, but is now assistant professor at Fox Chase Cancer Center in Philadelphia.
“We wanted to better understand how patients think about these trade-offs,” he said. “We found that they were less likely to choose treatments requiring more travel, or treatments that required them to transfer care to a new oncologist. This was the case, even if it meant choosing a treatment that might be less effective against their cancer. But when patients were offered a chance to have half of their follow-up appointments locally, travel was less of a barrier.”
Importantly, not all participants valued each aspect of treatments equally, Dr. Frosch noted, referencing the responses of Black versus White patients.
He and his colleagues stressed that while collaborative follow-up may ease access to more distant treatments for some patients, the lesser willingness among Black participants to travel for cancer therapy – regardless of follow-up arrangement – means that attention must be paid to unintended consequences, to avoid worsening the existing disparities in access to cellular therapies.
These data represent a step toward better understanding of how patients considering whether or not to travel for specialized cancer care weigh trade-offs, he said.
“However, we need to dig deeper into the issues we uncovered in future research, he added. “Our findings suggest that collaborative follow-up between the hospitals that offer these treatments and the oncologists in patients’ own communities could improve access to specialized cancer treatments. But I also think it’s important to understand that this may not be the solution for everyone, and so multiple and individualized strategies are going to be needed.”
Personalized treatment strategies
The findings provide important perspective on the need to address patients’ concerns and circumstances to improve access to cellular therapies, said Ankit Kansagra, MD, the Eugene P. Frenkel, M.D. Scholar in Clinical Medicine at the University of Texas Southwestern Medical Center, Dallas.
The unique focus by Dr. Frosch and his associates on the patient perspective versus the health care system perspective underscores the need to be patient-focused, and serves as a reminder that different strategies are needed for different patients, Dr. Kansagra, who has also conducted research on access to CAR T therapies, said in an interview.
For some patients, a shared model of care is much more important than a 5% improvement in survival, he said, adding that providers shouldn’t assume that they understand a patient’s perspective.
Devising hybrid solutions that take community and individual needs into consideration would be preferable to seeking one national solution for care access, he added.
“It’s also pretty clear from this that it can be a shared model versus just an academic center or community center doing everything,” he said. “I think that’s going to be the next frontier – [determining] how we can hand over a patient, once CAR T is done, back to the community oncologist so he or she can continue following the patient and knows the survivorship plan – and keeping that model in place.”
Next steps
Further work is needed to determine the mechanisms driving the differences observed between Black and White patients in this study, the authors said, explaining that “[a]lthough the differences observed by race may reflect structural racism-driven access inequities, the relatively small subsample of Black patients and model complexity constraints limited our ability to analyze multiple factors.
“A prospective validation study to demonstrate the association of stated preferences with real-world decisions would further support our findings,” they wrote.
Dr. Frosch reported having no conflicts of interest. Dr. Kansagra is on advisory boards for Alnylam, Bristol Myers Squibb, Cota Healthcare, GSK, Janssen, Oncopeptides, and Takeda.
, but other “multifaceted and personalized” strategies are also needed, a new study shows.
The findings, from a survey focused on patients’ willingness to travel for treatment, offer valuable insights on DLBCL patients’ perspectives and care needs, and on racial and sociodemographic variations among their perspectives and needs, the investigators said.
Treatment decision factors
They used a choice-based conjoint analysis to assess the relative value that 302 patients with DLBCL place on clinical factors, continuity of care, and travel time. Patients were asked to select treatment plans, choosing between pairs of hypothetical options that varied in travel time, follow-up arrangement, oncologist continuity, 2-year overall survival, and intensive care unit admission rate, the authors explained.
When all follow-up care in the hypothetical scenario was provided at the treatment center, plans requiring travel time of longer than 30 minutes were less attractive, Zachary A. K. Frosch, MD, and colleagues reported in the Journal of Clinical Oncology.
Importance weights, when compared with 30-minute travel time, were –0.54, –0.57, and –0.17 for 60, 90, and 120 minute travel time, they found.
However, scenarios involving shared follow-up by the treatment center and patients’ local providers mitigated the negative impact of travel on treatment plan choice, they noted (importance weights, 0.63, 0.32, and 0.26 at 60, 90, and 120-minute travel times).
Importantly, an analysis of responses based on sociodemographic factors showed that Black participants were less likely to choose plans requiring longer travel, regardless of follow-up arrangement, the authors said.
“Black patients were also less likely than White patients to choose treatment plans that offered lower continuity with their current oncologist (importance weights, 2.50 to vs. 1.09, respectively),” they wrote.
Further, when making choices that required trade-offs, treatment efficacy was a weaker driver of treatment plan preferences for Black patient than for White patients (importance weights, 0.34 vs. 0.75 per 5% point increase in overall survival, respectively).
Why the findings matter
“Certain cancer treatments aren’t offered everywhere. Examples of this are the bone marrow transplants and [chimeric antigen receptor T-cell] therapies used to treat patients with blood cancers such as lymphoma,” Dr. Frosch said in an interview, adding that the limited geographic availability of these treatments means that patients who need them may have to travel farther and also to establish care with a new oncologist.
“These are both things that some patients may be reluctant to do,” added Dr. Frosch, who was with the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, at the time of the study, but is now assistant professor at Fox Chase Cancer Center in Philadelphia.
“We wanted to better understand how patients think about these trade-offs,” he said. “We found that they were less likely to choose treatments requiring more travel, or treatments that required them to transfer care to a new oncologist. This was the case, even if it meant choosing a treatment that might be less effective against their cancer. But when patients were offered a chance to have half of their follow-up appointments locally, travel was less of a barrier.”
Importantly, not all participants valued each aspect of treatments equally, Dr. Frosch noted, referencing the responses of Black versus White patients.
He and his colleagues stressed that while collaborative follow-up may ease access to more distant treatments for some patients, the lesser willingness among Black participants to travel for cancer therapy – regardless of follow-up arrangement – means that attention must be paid to unintended consequences, to avoid worsening the existing disparities in access to cellular therapies.
These data represent a step toward better understanding of how patients considering whether or not to travel for specialized cancer care weigh trade-offs, he said.
“However, we need to dig deeper into the issues we uncovered in future research, he added. “Our findings suggest that collaborative follow-up between the hospitals that offer these treatments and the oncologists in patients’ own communities could improve access to specialized cancer treatments. But I also think it’s important to understand that this may not be the solution for everyone, and so multiple and individualized strategies are going to be needed.”
Personalized treatment strategies
The findings provide important perspective on the need to address patients’ concerns and circumstances to improve access to cellular therapies, said Ankit Kansagra, MD, the Eugene P. Frenkel, M.D. Scholar in Clinical Medicine at the University of Texas Southwestern Medical Center, Dallas.
The unique focus by Dr. Frosch and his associates on the patient perspective versus the health care system perspective underscores the need to be patient-focused, and serves as a reminder that different strategies are needed for different patients, Dr. Kansagra, who has also conducted research on access to CAR T therapies, said in an interview.
For some patients, a shared model of care is much more important than a 5% improvement in survival, he said, adding that providers shouldn’t assume that they understand a patient’s perspective.
Devising hybrid solutions that take community and individual needs into consideration would be preferable to seeking one national solution for care access, he added.
“It’s also pretty clear from this that it can be a shared model versus just an academic center or community center doing everything,” he said. “I think that’s going to be the next frontier – [determining] how we can hand over a patient, once CAR T is done, back to the community oncologist so he or she can continue following the patient and knows the survivorship plan – and keeping that model in place.”
Next steps
Further work is needed to determine the mechanisms driving the differences observed between Black and White patients in this study, the authors said, explaining that “[a]lthough the differences observed by race may reflect structural racism-driven access inequities, the relatively small subsample of Black patients and model complexity constraints limited our ability to analyze multiple factors.
“A prospective validation study to demonstrate the association of stated preferences with real-world decisions would further support our findings,” they wrote.
Dr. Frosch reported having no conflicts of interest. Dr. Kansagra is on advisory boards for Alnylam, Bristol Myers Squibb, Cota Healthcare, GSK, Janssen, Oncopeptides, and Takeda.
, but other “multifaceted and personalized” strategies are also needed, a new study shows.
The findings, from a survey focused on patients’ willingness to travel for treatment, offer valuable insights on DLBCL patients’ perspectives and care needs, and on racial and sociodemographic variations among their perspectives and needs, the investigators said.
Treatment decision factors
They used a choice-based conjoint analysis to assess the relative value that 302 patients with DLBCL place on clinical factors, continuity of care, and travel time. Patients were asked to select treatment plans, choosing between pairs of hypothetical options that varied in travel time, follow-up arrangement, oncologist continuity, 2-year overall survival, and intensive care unit admission rate, the authors explained.
When all follow-up care in the hypothetical scenario was provided at the treatment center, plans requiring travel time of longer than 30 minutes were less attractive, Zachary A. K. Frosch, MD, and colleagues reported in the Journal of Clinical Oncology.
Importance weights, when compared with 30-minute travel time, were –0.54, –0.57, and –0.17 for 60, 90, and 120 minute travel time, they found.
However, scenarios involving shared follow-up by the treatment center and patients’ local providers mitigated the negative impact of travel on treatment plan choice, they noted (importance weights, 0.63, 0.32, and 0.26 at 60, 90, and 120-minute travel times).
Importantly, an analysis of responses based on sociodemographic factors showed that Black participants were less likely to choose plans requiring longer travel, regardless of follow-up arrangement, the authors said.
“Black patients were also less likely than White patients to choose treatment plans that offered lower continuity with their current oncologist (importance weights, 2.50 to vs. 1.09, respectively),” they wrote.
Further, when making choices that required trade-offs, treatment efficacy was a weaker driver of treatment plan preferences for Black patient than for White patients (importance weights, 0.34 vs. 0.75 per 5% point increase in overall survival, respectively).
Why the findings matter
“Certain cancer treatments aren’t offered everywhere. Examples of this are the bone marrow transplants and [chimeric antigen receptor T-cell] therapies used to treat patients with blood cancers such as lymphoma,” Dr. Frosch said in an interview, adding that the limited geographic availability of these treatments means that patients who need them may have to travel farther and also to establish care with a new oncologist.
“These are both things that some patients may be reluctant to do,” added Dr. Frosch, who was with the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, at the time of the study, but is now assistant professor at Fox Chase Cancer Center in Philadelphia.
“We wanted to better understand how patients think about these trade-offs,” he said. “We found that they were less likely to choose treatments requiring more travel, or treatments that required them to transfer care to a new oncologist. This was the case, even if it meant choosing a treatment that might be less effective against their cancer. But when patients were offered a chance to have half of their follow-up appointments locally, travel was less of a barrier.”
Importantly, not all participants valued each aspect of treatments equally, Dr. Frosch noted, referencing the responses of Black versus White patients.
He and his colleagues stressed that while collaborative follow-up may ease access to more distant treatments for some patients, the lesser willingness among Black participants to travel for cancer therapy – regardless of follow-up arrangement – means that attention must be paid to unintended consequences, to avoid worsening the existing disparities in access to cellular therapies.
These data represent a step toward better understanding of how patients considering whether or not to travel for specialized cancer care weigh trade-offs, he said.
“However, we need to dig deeper into the issues we uncovered in future research, he added. “Our findings suggest that collaborative follow-up between the hospitals that offer these treatments and the oncologists in patients’ own communities could improve access to specialized cancer treatments. But I also think it’s important to understand that this may not be the solution for everyone, and so multiple and individualized strategies are going to be needed.”
Personalized treatment strategies
The findings provide important perspective on the need to address patients’ concerns and circumstances to improve access to cellular therapies, said Ankit Kansagra, MD, the Eugene P. Frenkel, M.D. Scholar in Clinical Medicine at the University of Texas Southwestern Medical Center, Dallas.
The unique focus by Dr. Frosch and his associates on the patient perspective versus the health care system perspective underscores the need to be patient-focused, and serves as a reminder that different strategies are needed for different patients, Dr. Kansagra, who has also conducted research on access to CAR T therapies, said in an interview.
For some patients, a shared model of care is much more important than a 5% improvement in survival, he said, adding that providers shouldn’t assume that they understand a patient’s perspective.
Devising hybrid solutions that take community and individual needs into consideration would be preferable to seeking one national solution for care access, he added.
“It’s also pretty clear from this that it can be a shared model versus just an academic center or community center doing everything,” he said. “I think that’s going to be the next frontier – [determining] how we can hand over a patient, once CAR T is done, back to the community oncologist so he or she can continue following the patient and knows the survivorship plan – and keeping that model in place.”
Next steps
Further work is needed to determine the mechanisms driving the differences observed between Black and White patients in this study, the authors said, explaining that “[a]lthough the differences observed by race may reflect structural racism-driven access inequities, the relatively small subsample of Black patients and model complexity constraints limited our ability to analyze multiple factors.
“A prospective validation study to demonstrate the association of stated preferences with real-world decisions would further support our findings,” they wrote.
Dr. Frosch reported having no conflicts of interest. Dr. Kansagra is on advisory boards for Alnylam, Bristol Myers Squibb, Cota Healthcare, GSK, Janssen, Oncopeptides, and Takeda.
FROM JCO
Most oncology trainees encounter discrimination, don’t report it, survey finds
On day 1 of her fellowship, Francesca C. Duncan, MD, was blindsided by her first patient.
The patient, a White man who was accompanied by his wife, sat in the exam room with his sunglasses on.
“I remember him saying, ‘I need to take off my sunglasses so you don’t look so Black,’” said Dr. Duncan, a pulmonologist and intensivist at Indiana University, Indianapolis, who has a specialty in lung cancer disparities.
The patient proceeded to grill her about her experience and training. He asked where she attended college and mocked her degree from a historically Black university. His wife sat there, silent.
Dr. Duncan was shocked by the fact that she still had to defend her credentials.
“I just kind of felt like at that point in my training, my title would have earned me more respect,” said Dr. Duncan, now an assistant professor after recently completing a 3-year fellowship in pulmonary and critical care medicine. “I thought at some point [the racism and discrimination] would stop, but after all that training, all that late-night studying, I still had to prove myself.”
Unfortunately, Dr. Duncan’s experience in fellowship is not unique.
A recent survey of hematology and oncology fellows revealed that medical trainees routinely encounter discrimination during their training.
The 17 fellows who were anonymously interviewed in the survey all recalled experiencing or witnessing discriminatory behaviors during their fellowship, mostly from patients. These encounters rarely come to light. Only one respondent officially reported an incident.
The findings, published online November 8 in JAMA Network Open, underscore the need for graduate medical education programs to improve learning environments and support for trainees, lead author Rahma M. Warsame, MD, and colleagues say .
Discrimination at work
Initially, Dr. Warsame and co–principal investigator Katharine Price, MD, were tasked with developing strategies to mitigate instances of racism and bias that fellows encountered during training, but both felt it was critical to understand the experiences of their trainees first.
Out of 34 fellows and recent graduates of the hematology and oncology fellowship program of the Mayo Clinic, Rochester, Minn., 20 consented to participate in the study. Of those, 17 were interviewed between July and November 2018. Among the 17 interviewees, six were Asian, two were Black, three were Hispanic, two were multiracial, and four were White.
The majority of these offenses were committed by patients, not faculty or other employees. The researchers largely interpreted most of the incidents as microaggressions.
From the interviews, the researchers identified six central themes. Among them: foreign fellows and U.S.-born trainees being perceived or made to feel like outsiders; inappropriate comments being made toward female employees about their looks, credentials, or marital status; lack of action after reporting incidents or concerns that reporting such incidents would be futile; and strategies fellows used to cope after negative interactions.
One interviewee said, “I was fired by a patient because I have an accent.” Another said that when she is interviewing for jobs, she is always asked if she has children: “Maybe they’re asking in an innocuous manner, but I always feel like people worry. Is this person going to take maternity leave and be less available for work?”
For Dr. Warsame, “the idea that American citizens were frequently made to feel like they do not belong was surprising.”
Not surprising to Dr. Warsame, however, was the importance of fostering diversity and inclusion during fellowship years. Fellows often noted that greater diversity within the program helped create a more inclusive environment.
“[What’s] important to reinforce is the value of creating platforms for honest discussion and intentionally seeking fellows’ voices and perspectives, which in turn makes them feel like they belong,” Dr. Warsame said.
Still, the researchers found that fellows often did not report incidents of discrimination or bias. Only six trainees were aware of policies for reporting patient misconduct or discrimination, and only one ever reported an incident.
Where’s the support?
For Dr. Duncan, her encounter 3 years ago with the patient with sunglasses wasn’t her first experience of discrimination on the job — or her last.
Although hurtful in the moment, she had the wherewithal to report the incident to her attending physician, who was equally shocked. Initially unsure of how to handle it, the attending ultimately stepped up and provided “immense support,” Dr. Duncan said
The issue was brought to the attention of the program director, who took swift action. The patient was documented as “disruptive,” informed of that status in writing, and was banned from receiving treatment from trainees at the center, although Dr. Duncan noted he still received the medical care he needed.
Often, however, fellows who report incidents of discrimination and racism receive little support. According to Dr. Warsame and colleagues, most trainees don’t bother reporting these experiences because they believe that doing so would be futile.
“Concerns about reporting included jeopardizing future employability, risk of retaliation, and challenges reporting experiences that could be perceived as subjective and difficult to prove,” the authors write.
For instance, one interviewee said: “I’m afraid to report these things because there’s gonna be repercussions. There’s no way it’s gonna be anonymous.... I just have to toughen up and, you know, get used [to it].”
Dr. Warsame added, “A major challenge for trainees was that they often felt unheard, and at the time, there was no formal debrief regarding discrimination issues when they arose.”
These instances of bias have implications for trainee well-being. In a 2019 study, discrimination that physicians and students experienced during training had adverse effects on their emotional health. Responses from 50 trainees and physicians revealed a wide range of discriminatory experiences, including patients rejecting care and spewing racist, sexist, or homophobic epithets. Many physicians were uncertain about how to respond effectively and appropriately.
Since that study was published and after having completed her own fellowship, Dr. Duncan said she has seen some change for the better.
“There is a lot more awareness around this, and programs are trying to do better in recognizing and responding to incidents,” she said. She noted that it’s important to ensure that those who are directly affected by discriminatory behaviors aren’t left to do all of the “heavy lifting” of addressing and resolving the issues.
The weight of discriminatory incidents, from microaggressions to overt racism, is cumulative and can adversely affect a person’s career. “It’s exhausting -- we need support,” she said.
The Mayo Clinic is working to ensure that trainees receive support. “The study has prompted communication workshops and faculty development to better equip trainees with strategies to address [and report] patients who behave or display disrespectful or discriminatory behavior,” Dr. Warsame said.
She and her colleagues noted that the anonymous hotline used for the survey cultivated a safe environment for candid discussions and that such an approach is “feasible and effective to explore sensitive topics and scalable to various geographic locations and different medical specialties.”
“We recognize that our program must seek this feedback regularly and ensure we keep a finger on the pulse of our trainees,” Dr. Warsame added.
Dr. Warsame and Dr. Duncan have disclosed no relevant financial relationships. Dr. Duncan noted that her views and comments are her own and do not necessarily reflect those of her institution.
A version of this article first appeared on Medscape.com.
On day 1 of her fellowship, Francesca C. Duncan, MD, was blindsided by her first patient.
The patient, a White man who was accompanied by his wife, sat in the exam room with his sunglasses on.
“I remember him saying, ‘I need to take off my sunglasses so you don’t look so Black,’” said Dr. Duncan, a pulmonologist and intensivist at Indiana University, Indianapolis, who has a specialty in lung cancer disparities.
The patient proceeded to grill her about her experience and training. He asked where she attended college and mocked her degree from a historically Black university. His wife sat there, silent.
Dr. Duncan was shocked by the fact that she still had to defend her credentials.
“I just kind of felt like at that point in my training, my title would have earned me more respect,” said Dr. Duncan, now an assistant professor after recently completing a 3-year fellowship in pulmonary and critical care medicine. “I thought at some point [the racism and discrimination] would stop, but after all that training, all that late-night studying, I still had to prove myself.”
Unfortunately, Dr. Duncan’s experience in fellowship is not unique.
A recent survey of hematology and oncology fellows revealed that medical trainees routinely encounter discrimination during their training.
The 17 fellows who were anonymously interviewed in the survey all recalled experiencing or witnessing discriminatory behaviors during their fellowship, mostly from patients. These encounters rarely come to light. Only one respondent officially reported an incident.
The findings, published online November 8 in JAMA Network Open, underscore the need for graduate medical education programs to improve learning environments and support for trainees, lead author Rahma M. Warsame, MD, and colleagues say .
Discrimination at work
Initially, Dr. Warsame and co–principal investigator Katharine Price, MD, were tasked with developing strategies to mitigate instances of racism and bias that fellows encountered during training, but both felt it was critical to understand the experiences of their trainees first.
Out of 34 fellows and recent graduates of the hematology and oncology fellowship program of the Mayo Clinic, Rochester, Minn., 20 consented to participate in the study. Of those, 17 were interviewed between July and November 2018. Among the 17 interviewees, six were Asian, two were Black, three were Hispanic, two were multiracial, and four were White.
The majority of these offenses were committed by patients, not faculty or other employees. The researchers largely interpreted most of the incidents as microaggressions.
From the interviews, the researchers identified six central themes. Among them: foreign fellows and U.S.-born trainees being perceived or made to feel like outsiders; inappropriate comments being made toward female employees about their looks, credentials, or marital status; lack of action after reporting incidents or concerns that reporting such incidents would be futile; and strategies fellows used to cope after negative interactions.
One interviewee said, “I was fired by a patient because I have an accent.” Another said that when she is interviewing for jobs, she is always asked if she has children: “Maybe they’re asking in an innocuous manner, but I always feel like people worry. Is this person going to take maternity leave and be less available for work?”
For Dr. Warsame, “the idea that American citizens were frequently made to feel like they do not belong was surprising.”
Not surprising to Dr. Warsame, however, was the importance of fostering diversity and inclusion during fellowship years. Fellows often noted that greater diversity within the program helped create a more inclusive environment.
“[What’s] important to reinforce is the value of creating platforms for honest discussion and intentionally seeking fellows’ voices and perspectives, which in turn makes them feel like they belong,” Dr. Warsame said.
Still, the researchers found that fellows often did not report incidents of discrimination or bias. Only six trainees were aware of policies for reporting patient misconduct or discrimination, and only one ever reported an incident.
Where’s the support?
For Dr. Duncan, her encounter 3 years ago with the patient with sunglasses wasn’t her first experience of discrimination on the job — or her last.
Although hurtful in the moment, she had the wherewithal to report the incident to her attending physician, who was equally shocked. Initially unsure of how to handle it, the attending ultimately stepped up and provided “immense support,” Dr. Duncan said
The issue was brought to the attention of the program director, who took swift action. The patient was documented as “disruptive,” informed of that status in writing, and was banned from receiving treatment from trainees at the center, although Dr. Duncan noted he still received the medical care he needed.
Often, however, fellows who report incidents of discrimination and racism receive little support. According to Dr. Warsame and colleagues, most trainees don’t bother reporting these experiences because they believe that doing so would be futile.
“Concerns about reporting included jeopardizing future employability, risk of retaliation, and challenges reporting experiences that could be perceived as subjective and difficult to prove,” the authors write.
For instance, one interviewee said: “I’m afraid to report these things because there’s gonna be repercussions. There’s no way it’s gonna be anonymous.... I just have to toughen up and, you know, get used [to it].”
Dr. Warsame added, “A major challenge for trainees was that they often felt unheard, and at the time, there was no formal debrief regarding discrimination issues when they arose.”
These instances of bias have implications for trainee well-being. In a 2019 study, discrimination that physicians and students experienced during training had adverse effects on their emotional health. Responses from 50 trainees and physicians revealed a wide range of discriminatory experiences, including patients rejecting care and spewing racist, sexist, or homophobic epithets. Many physicians were uncertain about how to respond effectively and appropriately.
Since that study was published and after having completed her own fellowship, Dr. Duncan said she has seen some change for the better.
“There is a lot more awareness around this, and programs are trying to do better in recognizing and responding to incidents,” she said. She noted that it’s important to ensure that those who are directly affected by discriminatory behaviors aren’t left to do all of the “heavy lifting” of addressing and resolving the issues.
The weight of discriminatory incidents, from microaggressions to overt racism, is cumulative and can adversely affect a person’s career. “It’s exhausting -- we need support,” she said.
The Mayo Clinic is working to ensure that trainees receive support. “The study has prompted communication workshops and faculty development to better equip trainees with strategies to address [and report] patients who behave or display disrespectful or discriminatory behavior,” Dr. Warsame said.
She and her colleagues noted that the anonymous hotline used for the survey cultivated a safe environment for candid discussions and that such an approach is “feasible and effective to explore sensitive topics and scalable to various geographic locations and different medical specialties.”
“We recognize that our program must seek this feedback regularly and ensure we keep a finger on the pulse of our trainees,” Dr. Warsame added.
Dr. Warsame and Dr. Duncan have disclosed no relevant financial relationships. Dr. Duncan noted that her views and comments are her own and do not necessarily reflect those of her institution.
A version of this article first appeared on Medscape.com.
On day 1 of her fellowship, Francesca C. Duncan, MD, was blindsided by her first patient.
The patient, a White man who was accompanied by his wife, sat in the exam room with his sunglasses on.
“I remember him saying, ‘I need to take off my sunglasses so you don’t look so Black,’” said Dr. Duncan, a pulmonologist and intensivist at Indiana University, Indianapolis, who has a specialty in lung cancer disparities.
The patient proceeded to grill her about her experience and training. He asked where she attended college and mocked her degree from a historically Black university. His wife sat there, silent.
Dr. Duncan was shocked by the fact that she still had to defend her credentials.
“I just kind of felt like at that point in my training, my title would have earned me more respect,” said Dr. Duncan, now an assistant professor after recently completing a 3-year fellowship in pulmonary and critical care medicine. “I thought at some point [the racism and discrimination] would stop, but after all that training, all that late-night studying, I still had to prove myself.”
Unfortunately, Dr. Duncan’s experience in fellowship is not unique.
A recent survey of hematology and oncology fellows revealed that medical trainees routinely encounter discrimination during their training.
The 17 fellows who were anonymously interviewed in the survey all recalled experiencing or witnessing discriminatory behaviors during their fellowship, mostly from patients. These encounters rarely come to light. Only one respondent officially reported an incident.
The findings, published online November 8 in JAMA Network Open, underscore the need for graduate medical education programs to improve learning environments and support for trainees, lead author Rahma M. Warsame, MD, and colleagues say .
Discrimination at work
Initially, Dr. Warsame and co–principal investigator Katharine Price, MD, were tasked with developing strategies to mitigate instances of racism and bias that fellows encountered during training, but both felt it was critical to understand the experiences of their trainees first.
Out of 34 fellows and recent graduates of the hematology and oncology fellowship program of the Mayo Clinic, Rochester, Minn., 20 consented to participate in the study. Of those, 17 were interviewed between July and November 2018. Among the 17 interviewees, six were Asian, two were Black, three were Hispanic, two were multiracial, and four were White.
The majority of these offenses were committed by patients, not faculty or other employees. The researchers largely interpreted most of the incidents as microaggressions.
From the interviews, the researchers identified six central themes. Among them: foreign fellows and U.S.-born trainees being perceived or made to feel like outsiders; inappropriate comments being made toward female employees about their looks, credentials, or marital status; lack of action after reporting incidents or concerns that reporting such incidents would be futile; and strategies fellows used to cope after negative interactions.
One interviewee said, “I was fired by a patient because I have an accent.” Another said that when she is interviewing for jobs, she is always asked if she has children: “Maybe they’re asking in an innocuous manner, but I always feel like people worry. Is this person going to take maternity leave and be less available for work?”
For Dr. Warsame, “the idea that American citizens were frequently made to feel like they do not belong was surprising.”
Not surprising to Dr. Warsame, however, was the importance of fostering diversity and inclusion during fellowship years. Fellows often noted that greater diversity within the program helped create a more inclusive environment.
“[What’s] important to reinforce is the value of creating platforms for honest discussion and intentionally seeking fellows’ voices and perspectives, which in turn makes them feel like they belong,” Dr. Warsame said.
Still, the researchers found that fellows often did not report incidents of discrimination or bias. Only six trainees were aware of policies for reporting patient misconduct or discrimination, and only one ever reported an incident.
Where’s the support?
For Dr. Duncan, her encounter 3 years ago with the patient with sunglasses wasn’t her first experience of discrimination on the job — or her last.
Although hurtful in the moment, she had the wherewithal to report the incident to her attending physician, who was equally shocked. Initially unsure of how to handle it, the attending ultimately stepped up and provided “immense support,” Dr. Duncan said
The issue was brought to the attention of the program director, who took swift action. The patient was documented as “disruptive,” informed of that status in writing, and was banned from receiving treatment from trainees at the center, although Dr. Duncan noted he still received the medical care he needed.
Often, however, fellows who report incidents of discrimination and racism receive little support. According to Dr. Warsame and colleagues, most trainees don’t bother reporting these experiences because they believe that doing so would be futile.
“Concerns about reporting included jeopardizing future employability, risk of retaliation, and challenges reporting experiences that could be perceived as subjective and difficult to prove,” the authors write.
For instance, one interviewee said: “I’m afraid to report these things because there’s gonna be repercussions. There’s no way it’s gonna be anonymous.... I just have to toughen up and, you know, get used [to it].”
Dr. Warsame added, “A major challenge for trainees was that they often felt unheard, and at the time, there was no formal debrief regarding discrimination issues when they arose.”
These instances of bias have implications for trainee well-being. In a 2019 study, discrimination that physicians and students experienced during training had adverse effects on their emotional health. Responses from 50 trainees and physicians revealed a wide range of discriminatory experiences, including patients rejecting care and spewing racist, sexist, or homophobic epithets. Many physicians were uncertain about how to respond effectively and appropriately.
Since that study was published and after having completed her own fellowship, Dr. Duncan said she has seen some change for the better.
“There is a lot more awareness around this, and programs are trying to do better in recognizing and responding to incidents,” she said. She noted that it’s important to ensure that those who are directly affected by discriminatory behaviors aren’t left to do all of the “heavy lifting” of addressing and resolving the issues.
The weight of discriminatory incidents, from microaggressions to overt racism, is cumulative and can adversely affect a person’s career. “It’s exhausting -- we need support,” she said.
The Mayo Clinic is working to ensure that trainees receive support. “The study has prompted communication workshops and faculty development to better equip trainees with strategies to address [and report] patients who behave or display disrespectful or discriminatory behavior,” Dr. Warsame said.
She and her colleagues noted that the anonymous hotline used for the survey cultivated a safe environment for candid discussions and that such an approach is “feasible and effective to explore sensitive topics and scalable to various geographic locations and different medical specialties.”
“We recognize that our program must seek this feedback regularly and ensure we keep a finger on the pulse of our trainees,” Dr. Warsame added.
Dr. Warsame and Dr. Duncan have disclosed no relevant financial relationships. Dr. Duncan noted that her views and comments are her own and do not necessarily reflect those of her institution.
A version of this article first appeared on Medscape.com.
Cancer drug revenue increased 70% over a decade
Cumulative annual revenue from cancer drug sales increased by 70% among the world’s largest pharmaceutical companies over the past decade, a retrospective analysis shows.
By comparison, revenues from other types of medications decreased by 18% during the same period.
“Cancer drugs now account for approximately 27% of new drug approvals in the United States, compared to 4% in the 1980s. During this period, there has also been a substantial increase in the price of cancer medicines,” Daniel E. Myers, MD, of the University of Calgary, Canada, and colleagues explain in their report, published online October 6 in Cancer.
To investigate the impact of these trends on pharmaceutical earnings, the investigators performed a retrospective analysis of the revenue generated from oncology drugs in comparison with total drug revenue among 10 large pharmaceutical companies between 2010 and 2019, using itemized product-sales data publicly available through company websites or annual filings.
The data, adjusted for inflation and converted to 2019 U.S. dollars, revealed that annual revenue for the 10 companies increased from $55.8 billion to $95.1 billion during the study period. Most of the growth in revenue occurred in the past 5 years. Over the decade, non-oncology drug revenue decreased by 18% – from $342.2 billion to $281.5 billion.
Overall, revenues from cancer drugs accounted for 25% of the net revenues generated by these companies in 2019, up from 14% in 2010. Roche had both the highest net revenue – $23.9 billion in 2010 and $27.7 billion in 2019 – and the greatest proportion of revenue from cancer drugs – 63.5% in 2016 and 57% in 2019.
Merck saw substantial growth in revenue from cancer drug sales, particularly between 2016 and 2019. In 2016, the company generated $2.4 billion from these medicines, representing 6% of total revenue. By 2019, that amount had grown to $12.3 billion, representing almost 30% of total revenue. This increase was driven largely by their drug pembrolizumab, which alone drew in about $11 billion in 2019, or 12% of total oncology revenue, the investigators note.
Sanofi and GSK had some of the lowest net revenues from cancer drugs during the study period. For instance, in 2019, GSK generated $300 million in revenue from oncology drugs, representing less than 1% of the company’s total revenue, down from 3% of its total revenue in 2010.
“With the cost of cancer drugs rapidly rising, further work is needed to understand how this [overall] increase in sales revenue reflects industry profit, and how this is linked (or not) to improvements in patient and population outcomes,” they conclude. Although data regarding how cancer drug development affects population mortality rates are limited, “there is a notion within biomedicine that rising corporate profitability may not translate into proportional societal gains.”
No funding for the study has been disclosed. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Cumulative annual revenue from cancer drug sales increased by 70% among the world’s largest pharmaceutical companies over the past decade, a retrospective analysis shows.
By comparison, revenues from other types of medications decreased by 18% during the same period.
“Cancer drugs now account for approximately 27% of new drug approvals in the United States, compared to 4% in the 1980s. During this period, there has also been a substantial increase in the price of cancer medicines,” Daniel E. Myers, MD, of the University of Calgary, Canada, and colleagues explain in their report, published online October 6 in Cancer.
To investigate the impact of these trends on pharmaceutical earnings, the investigators performed a retrospective analysis of the revenue generated from oncology drugs in comparison with total drug revenue among 10 large pharmaceutical companies between 2010 and 2019, using itemized product-sales data publicly available through company websites or annual filings.
The data, adjusted for inflation and converted to 2019 U.S. dollars, revealed that annual revenue for the 10 companies increased from $55.8 billion to $95.1 billion during the study period. Most of the growth in revenue occurred in the past 5 years. Over the decade, non-oncology drug revenue decreased by 18% – from $342.2 billion to $281.5 billion.
Overall, revenues from cancer drugs accounted for 25% of the net revenues generated by these companies in 2019, up from 14% in 2010. Roche had both the highest net revenue – $23.9 billion in 2010 and $27.7 billion in 2019 – and the greatest proportion of revenue from cancer drugs – 63.5% in 2016 and 57% in 2019.
Merck saw substantial growth in revenue from cancer drug sales, particularly between 2016 and 2019. In 2016, the company generated $2.4 billion from these medicines, representing 6% of total revenue. By 2019, that amount had grown to $12.3 billion, representing almost 30% of total revenue. This increase was driven largely by their drug pembrolizumab, which alone drew in about $11 billion in 2019, or 12% of total oncology revenue, the investigators note.
Sanofi and GSK had some of the lowest net revenues from cancer drugs during the study period. For instance, in 2019, GSK generated $300 million in revenue from oncology drugs, representing less than 1% of the company’s total revenue, down from 3% of its total revenue in 2010.
“With the cost of cancer drugs rapidly rising, further work is needed to understand how this [overall] increase in sales revenue reflects industry profit, and how this is linked (or not) to improvements in patient and population outcomes,” they conclude. Although data regarding how cancer drug development affects population mortality rates are limited, “there is a notion within biomedicine that rising corporate profitability may not translate into proportional societal gains.”
No funding for the study has been disclosed. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Cumulative annual revenue from cancer drug sales increased by 70% among the world’s largest pharmaceutical companies over the past decade, a retrospective analysis shows.
By comparison, revenues from other types of medications decreased by 18% during the same period.
“Cancer drugs now account for approximately 27% of new drug approvals in the United States, compared to 4% in the 1980s. During this period, there has also been a substantial increase in the price of cancer medicines,” Daniel E. Myers, MD, of the University of Calgary, Canada, and colleagues explain in their report, published online October 6 in Cancer.
To investigate the impact of these trends on pharmaceutical earnings, the investigators performed a retrospective analysis of the revenue generated from oncology drugs in comparison with total drug revenue among 10 large pharmaceutical companies between 2010 and 2019, using itemized product-sales data publicly available through company websites or annual filings.
The data, adjusted for inflation and converted to 2019 U.S. dollars, revealed that annual revenue for the 10 companies increased from $55.8 billion to $95.1 billion during the study period. Most of the growth in revenue occurred in the past 5 years. Over the decade, non-oncology drug revenue decreased by 18% – from $342.2 billion to $281.5 billion.
Overall, revenues from cancer drugs accounted for 25% of the net revenues generated by these companies in 2019, up from 14% in 2010. Roche had both the highest net revenue – $23.9 billion in 2010 and $27.7 billion in 2019 – and the greatest proportion of revenue from cancer drugs – 63.5% in 2016 and 57% in 2019.
Merck saw substantial growth in revenue from cancer drug sales, particularly between 2016 and 2019. In 2016, the company generated $2.4 billion from these medicines, representing 6% of total revenue. By 2019, that amount had grown to $12.3 billion, representing almost 30% of total revenue. This increase was driven largely by their drug pembrolizumab, which alone drew in about $11 billion in 2019, or 12% of total oncology revenue, the investigators note.
Sanofi and GSK had some of the lowest net revenues from cancer drugs during the study period. For instance, in 2019, GSK generated $300 million in revenue from oncology drugs, representing less than 1% of the company’s total revenue, down from 3% of its total revenue in 2010.
“With the cost of cancer drugs rapidly rising, further work is needed to understand how this [overall] increase in sales revenue reflects industry profit, and how this is linked (or not) to improvements in patient and population outcomes,” they conclude. Although data regarding how cancer drug development affects population mortality rates are limited, “there is a notion within biomedicine that rising corporate profitability may not translate into proportional societal gains.”
No funding for the study has been disclosed. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Should you tell your doctor that you’re a doctor?
The question drew spirited debate when urologist Ashley Winter, MD, made a simple, straightforward request on Twitter: “If you are a doctor & you come to an appointment please tell me you are a doctor, not because I will treat you differently but because it’s easier to speak in jargon.”
She later added, “This doesn’t’ mean I would be less patient-focused or emotional with a physician or other [healthcare worker]. Just means that, instead of saying ‘you will have a catheter draining your urine to a bag,’ I can say, ‘you will have a Foley.’ ”
The Tweet followed an encounter with a patient who told Dr. Winter that he was a doctor only after she had gone to some length explaining a surgical procedure in lay terms.
“I explained the surgery, obviously assuming he was an intelligent adult, but using fully layman’s terms,” she said in an interview. The patient then told her that he was a doctor. “I guess I felt this embarrassment — I wouldn’t have treated him differently, but I just could have discussed the procedure with him in more professional terms.”
“To some extent, it was my own fault,” she commented in an interview. “I didn’t take the time to ask [about his work] at the beginning of the consultation, but that’s a fine line, also,” added Dr. Winter, a urologist and sexual medicine physician in Portland, Ore.
“You know that patient is there because they want care from you and it’s not necessarily always at the forefront of importance to be asking them what they do for their work, but alternatively, if you don’t ask then you put them in this position where they have to find a way to go ahead and tell you.”
Several people chimed in on the thread to voice their thoughts on the matter. Some commiserated with Dr. Winter’s experience:
“I took care of a retired cardiologist in the hospital as a second-year resident and honest to god he let me ramble on ‘explaining’ his echo result and never told me. I found out a couple days later and wanted to die,” posted @MaddyAndrewsMD.
Another recalled a similarly embarrassing experience when she “went on and on” discussing headaches with a patient whose husband “was in the corner smirking.”
“They told my attending later [that the] husband was a retired FM doc who practiced medicine longer than I’ve been alive. I wanted to die,” posted @JSinghDO.
Many on the thread, though, were doctors and other healthcare professionals speaking as patients. Some said they didn’t want to disclose their status as a healthcare provider because they felt it affected the care they received.
For example, @drhelenrainford commented: “In my experience my care is less ‘caring’ when they know I am a [doctor]. I get spoken to like they are discussing a patient with me — no empathy just facts and difficult results just blurted out without consideration. Awful awful time as an inpatient …but that’s another story!”
@Dr_B_Ring said: “Nope – You and I speak different jargon – I would want you to speak to me like a human that doesn’t know your jargon. My ego would get in the way of asking about the acronyms I don’t know if you knew I was a fellow physician.”
Conversely, @lozzlemcfozzle said: “Honestly I prefer not to tell my Doctors — I’ve found people skip explanations assuming I ‘know,’ or seem a little nervous when I tell them!”
Others said they felt uncomfortable — pretentious, even — in announcing their status, or worried that they might come across as expecting special care.
“It’s such a tough needle to thread. Want to tell people early but not come off as demanding special treatment, but don’t want to wait too long and it seems like a trap,” said @MDaware.
Twitter user @MsBabyCatcher wrote: “I have a hard time doing this because I don’t want people to think I’m being pretentious or going to micromanage/dictate care.”
Replying to @MsBabyCatcher, @RedStethoscope wrote: “I used to think this too until I got [very poor] care a few times, and was advised by other doctor moms to ‘play the doctor card.’ I have gotten better/more compassionate care by making sure it’s clear that I’m a physician (which is junk, but here we are).”
Several of those responding used the words “tricky” and “awkward,” suggesting a common theme for doctors presenting as patients.
“I struggle with this. My 5-year-old broke her arm this weekend, we spent hours in the ED, of my own hospital, I never mentioned it because I didn’t want to get preferential care. But as they were explaining her type of fracture, it felt awkward and inefficient,” said @lindsay_petty.
To avoid the awkwardness, a number of respondents said they purposefully use medical jargon to open up a conversation rather than just offering up the information that they are a doctor.
Still others offered suggestions on how to broach the subject more directly when presenting as a patient:
‘”Just FYI I’m a X doc but I’m here because I really want your help and advice!” That’s what I usually do,” wrote @drcakefm.
@BeeSting14618 Tweeted: “I usually say ‘I know some of this but I’m here because I want YOUR guidance. Also I may ask dumb questions, and I’ll tell you if a question is asking your opinion or making a request.’”
A few others injected a bit of humor: “I just do the 14-part handshake that only doctors know. Is that not customary?” quipped @Branmiz25.
“Ah yes, that transmits the entire [history of present illness],” replied Dr. Winter.
Jokes aside, the topic is obviously one that touched on a shared experience among healthcare providers, Dr. Winter commented. The Twitter thread she started just “blew up.”
That’s typically a sign that the Tweet is relatable for a lot of people, she said.
“It’s definitely something that all of us as care providers and as patients understand. It’s a funny, awkward thing that can really change an interaction, so we probably all feel pretty strongly about our experiences related to that,” she added.
The debate begs the question: Is there a duty or ethical reason to disclose?
“I definitely think it is very reasonable to disclose that one is a medical professional to another doctor,” medical ethicist Charlotte Blease, PhD, said in an interview. “There are good reasons to believe doing so might make a difference to the quality of communication and transparency.”
If the ability to use medical terminology or jargon more freely improves patient understanding, autonomy, and shared decision-making, then it may be of benefit, said Dr. Blease, a Keane OpenNotes Scholar at Beth Israel Deaconess Medical Center in Boston.
“Since doctors should strive to communicate effectively with every patient and to respect their unique needs and level of understanding, then I see no reason to deny that one is a medic,” she added.”
Knowing how to share the information is another story.
“This is something that affects all of us as physicians — we’re going to be patients at some point, right?” Dr. Winter commented. “But I don’t think how to disclose that is something that was ever brought up in my medical training.”
“Maybe there should just be a discussion of this one day when people are in medical school — maybe in a professionalism course — to broach this topic or look at if there’s any literature on outcomes related to disclosure of status or what are best practices,” she suggested.
A version of this article first appeared on Medscape.com.
The question drew spirited debate when urologist Ashley Winter, MD, made a simple, straightforward request on Twitter: “If you are a doctor & you come to an appointment please tell me you are a doctor, not because I will treat you differently but because it’s easier to speak in jargon.”
She later added, “This doesn’t’ mean I would be less patient-focused or emotional with a physician or other [healthcare worker]. Just means that, instead of saying ‘you will have a catheter draining your urine to a bag,’ I can say, ‘you will have a Foley.’ ”
The Tweet followed an encounter with a patient who told Dr. Winter that he was a doctor only after she had gone to some length explaining a surgical procedure in lay terms.
“I explained the surgery, obviously assuming he was an intelligent adult, but using fully layman’s terms,” she said in an interview. The patient then told her that he was a doctor. “I guess I felt this embarrassment — I wouldn’t have treated him differently, but I just could have discussed the procedure with him in more professional terms.”
“To some extent, it was my own fault,” she commented in an interview. “I didn’t take the time to ask [about his work] at the beginning of the consultation, but that’s a fine line, also,” added Dr. Winter, a urologist and sexual medicine physician in Portland, Ore.
“You know that patient is there because they want care from you and it’s not necessarily always at the forefront of importance to be asking them what they do for their work, but alternatively, if you don’t ask then you put them in this position where they have to find a way to go ahead and tell you.”
Several people chimed in on the thread to voice their thoughts on the matter. Some commiserated with Dr. Winter’s experience:
“I took care of a retired cardiologist in the hospital as a second-year resident and honest to god he let me ramble on ‘explaining’ his echo result and never told me. I found out a couple days later and wanted to die,” posted @MaddyAndrewsMD.
Another recalled a similarly embarrassing experience when she “went on and on” discussing headaches with a patient whose husband “was in the corner smirking.”
“They told my attending later [that the] husband was a retired FM doc who practiced medicine longer than I’ve been alive. I wanted to die,” posted @JSinghDO.
Many on the thread, though, were doctors and other healthcare professionals speaking as patients. Some said they didn’t want to disclose their status as a healthcare provider because they felt it affected the care they received.
For example, @drhelenrainford commented: “In my experience my care is less ‘caring’ when they know I am a [doctor]. I get spoken to like they are discussing a patient with me — no empathy just facts and difficult results just blurted out without consideration. Awful awful time as an inpatient …but that’s another story!”
@Dr_B_Ring said: “Nope – You and I speak different jargon – I would want you to speak to me like a human that doesn’t know your jargon. My ego would get in the way of asking about the acronyms I don’t know if you knew I was a fellow physician.”
Conversely, @lozzlemcfozzle said: “Honestly I prefer not to tell my Doctors — I’ve found people skip explanations assuming I ‘know,’ or seem a little nervous when I tell them!”
Others said they felt uncomfortable — pretentious, even — in announcing their status, or worried that they might come across as expecting special care.
“It’s such a tough needle to thread. Want to tell people early but not come off as demanding special treatment, but don’t want to wait too long and it seems like a trap,” said @MDaware.
Twitter user @MsBabyCatcher wrote: “I have a hard time doing this because I don’t want people to think I’m being pretentious or going to micromanage/dictate care.”
Replying to @MsBabyCatcher, @RedStethoscope wrote: “I used to think this too until I got [very poor] care a few times, and was advised by other doctor moms to ‘play the doctor card.’ I have gotten better/more compassionate care by making sure it’s clear that I’m a physician (which is junk, but here we are).”
Several of those responding used the words “tricky” and “awkward,” suggesting a common theme for doctors presenting as patients.
“I struggle with this. My 5-year-old broke her arm this weekend, we spent hours in the ED, of my own hospital, I never mentioned it because I didn’t want to get preferential care. But as they were explaining her type of fracture, it felt awkward and inefficient,” said @lindsay_petty.
To avoid the awkwardness, a number of respondents said they purposefully use medical jargon to open up a conversation rather than just offering up the information that they are a doctor.
Still others offered suggestions on how to broach the subject more directly when presenting as a patient:
‘”Just FYI I’m a X doc but I’m here because I really want your help and advice!” That’s what I usually do,” wrote @drcakefm.
@BeeSting14618 Tweeted: “I usually say ‘I know some of this but I’m here because I want YOUR guidance. Also I may ask dumb questions, and I’ll tell you if a question is asking your opinion or making a request.’”
A few others injected a bit of humor: “I just do the 14-part handshake that only doctors know. Is that not customary?” quipped @Branmiz25.
“Ah yes, that transmits the entire [history of present illness],” replied Dr. Winter.
Jokes aside, the topic is obviously one that touched on a shared experience among healthcare providers, Dr. Winter commented. The Twitter thread she started just “blew up.”
That’s typically a sign that the Tweet is relatable for a lot of people, she said.
“It’s definitely something that all of us as care providers and as patients understand. It’s a funny, awkward thing that can really change an interaction, so we probably all feel pretty strongly about our experiences related to that,” she added.
The debate begs the question: Is there a duty or ethical reason to disclose?
“I definitely think it is very reasonable to disclose that one is a medical professional to another doctor,” medical ethicist Charlotte Blease, PhD, said in an interview. “There are good reasons to believe doing so might make a difference to the quality of communication and transparency.”
If the ability to use medical terminology or jargon more freely improves patient understanding, autonomy, and shared decision-making, then it may be of benefit, said Dr. Blease, a Keane OpenNotes Scholar at Beth Israel Deaconess Medical Center in Boston.
“Since doctors should strive to communicate effectively with every patient and to respect their unique needs and level of understanding, then I see no reason to deny that one is a medic,” she added.”
Knowing how to share the information is another story.
“This is something that affects all of us as physicians — we’re going to be patients at some point, right?” Dr. Winter commented. “But I don’t think how to disclose that is something that was ever brought up in my medical training.”
“Maybe there should just be a discussion of this one day when people are in medical school — maybe in a professionalism course — to broach this topic or look at if there’s any literature on outcomes related to disclosure of status or what are best practices,” she suggested.
A version of this article first appeared on Medscape.com.
The question drew spirited debate when urologist Ashley Winter, MD, made a simple, straightforward request on Twitter: “If you are a doctor & you come to an appointment please tell me you are a doctor, not because I will treat you differently but because it’s easier to speak in jargon.”
She later added, “This doesn’t’ mean I would be less patient-focused or emotional with a physician or other [healthcare worker]. Just means that, instead of saying ‘you will have a catheter draining your urine to a bag,’ I can say, ‘you will have a Foley.’ ”
The Tweet followed an encounter with a patient who told Dr. Winter that he was a doctor only after she had gone to some length explaining a surgical procedure in lay terms.
“I explained the surgery, obviously assuming he was an intelligent adult, but using fully layman’s terms,” she said in an interview. The patient then told her that he was a doctor. “I guess I felt this embarrassment — I wouldn’t have treated him differently, but I just could have discussed the procedure with him in more professional terms.”
“To some extent, it was my own fault,” she commented in an interview. “I didn’t take the time to ask [about his work] at the beginning of the consultation, but that’s a fine line, also,” added Dr. Winter, a urologist and sexual medicine physician in Portland, Ore.
“You know that patient is there because they want care from you and it’s not necessarily always at the forefront of importance to be asking them what they do for their work, but alternatively, if you don’t ask then you put them in this position where they have to find a way to go ahead and tell you.”
Several people chimed in on the thread to voice their thoughts on the matter. Some commiserated with Dr. Winter’s experience:
“I took care of a retired cardiologist in the hospital as a second-year resident and honest to god he let me ramble on ‘explaining’ his echo result and never told me. I found out a couple days later and wanted to die,” posted @MaddyAndrewsMD.
Another recalled a similarly embarrassing experience when she “went on and on” discussing headaches with a patient whose husband “was in the corner smirking.”
“They told my attending later [that the] husband was a retired FM doc who practiced medicine longer than I’ve been alive. I wanted to die,” posted @JSinghDO.
Many on the thread, though, were doctors and other healthcare professionals speaking as patients. Some said they didn’t want to disclose their status as a healthcare provider because they felt it affected the care they received.
For example, @drhelenrainford commented: “In my experience my care is less ‘caring’ when they know I am a [doctor]. I get spoken to like they are discussing a patient with me — no empathy just facts and difficult results just blurted out without consideration. Awful awful time as an inpatient …but that’s another story!”
@Dr_B_Ring said: “Nope – You and I speak different jargon – I would want you to speak to me like a human that doesn’t know your jargon. My ego would get in the way of asking about the acronyms I don’t know if you knew I was a fellow physician.”
Conversely, @lozzlemcfozzle said: “Honestly I prefer not to tell my Doctors — I’ve found people skip explanations assuming I ‘know,’ or seem a little nervous when I tell them!”
Others said they felt uncomfortable — pretentious, even — in announcing their status, or worried that they might come across as expecting special care.
“It’s such a tough needle to thread. Want to tell people early but not come off as demanding special treatment, but don’t want to wait too long and it seems like a trap,” said @MDaware.
Twitter user @MsBabyCatcher wrote: “I have a hard time doing this because I don’t want people to think I’m being pretentious or going to micromanage/dictate care.”
Replying to @MsBabyCatcher, @RedStethoscope wrote: “I used to think this too until I got [very poor] care a few times, and was advised by other doctor moms to ‘play the doctor card.’ I have gotten better/more compassionate care by making sure it’s clear that I’m a physician (which is junk, but here we are).”
Several of those responding used the words “tricky” and “awkward,” suggesting a common theme for doctors presenting as patients.
“I struggle with this. My 5-year-old broke her arm this weekend, we spent hours in the ED, of my own hospital, I never mentioned it because I didn’t want to get preferential care. But as they were explaining her type of fracture, it felt awkward and inefficient,” said @lindsay_petty.
To avoid the awkwardness, a number of respondents said they purposefully use medical jargon to open up a conversation rather than just offering up the information that they are a doctor.
Still others offered suggestions on how to broach the subject more directly when presenting as a patient:
‘”Just FYI I’m a X doc but I’m here because I really want your help and advice!” That’s what I usually do,” wrote @drcakefm.
@BeeSting14618 Tweeted: “I usually say ‘I know some of this but I’m here because I want YOUR guidance. Also I may ask dumb questions, and I’ll tell you if a question is asking your opinion or making a request.’”
A few others injected a bit of humor: “I just do the 14-part handshake that only doctors know. Is that not customary?” quipped @Branmiz25.
“Ah yes, that transmits the entire [history of present illness],” replied Dr. Winter.
Jokes aside, the topic is obviously one that touched on a shared experience among healthcare providers, Dr. Winter commented. The Twitter thread she started just “blew up.”
That’s typically a sign that the Tweet is relatable for a lot of people, she said.
“It’s definitely something that all of us as care providers and as patients understand. It’s a funny, awkward thing that can really change an interaction, so we probably all feel pretty strongly about our experiences related to that,” she added.
The debate begs the question: Is there a duty or ethical reason to disclose?
“I definitely think it is very reasonable to disclose that one is a medical professional to another doctor,” medical ethicist Charlotte Blease, PhD, said in an interview. “There are good reasons to believe doing so might make a difference to the quality of communication and transparency.”
If the ability to use medical terminology or jargon more freely improves patient understanding, autonomy, and shared decision-making, then it may be of benefit, said Dr. Blease, a Keane OpenNotes Scholar at Beth Israel Deaconess Medical Center in Boston.
“Since doctors should strive to communicate effectively with every patient and to respect their unique needs and level of understanding, then I see no reason to deny that one is a medic,” she added.”
Knowing how to share the information is another story.
“This is something that affects all of us as physicians — we’re going to be patients at some point, right?” Dr. Winter commented. “But I don’t think how to disclose that is something that was ever brought up in my medical training.”
“Maybe there should just be a discussion of this one day when people are in medical school — maybe in a professionalism course — to broach this topic or look at if there’s any literature on outcomes related to disclosure of status or what are best practices,” she suggested.
A version of this article first appeared on Medscape.com.
Data from Spain yield new insights on a rare hemophilia
The findings also indicate that an unusually large proportion of patients were on antithrombotic therapy, which may have led to misdiagnosis or delayed diagnosis of acquired hemophilia A (AHA) in some cases, Marıa-Eva Mingot-Castellano, MD, PhD, of Hospital Universitario Virgen del Rocıo, Seville, Spain, and Hospital Regional Universitario de Malaga (Spain) and colleagues reported on behalf of the Acquired Haemophilia-A Spanish Registry (AHASR).
The report was published online in Blood Advances.
These data provide useful clinical information about a rare disease, and they underscore the need for vigilance when prescribing immunosuppressive therapy for frail, elderly patients with AHA, hematologist Nigel Key, MD, said in an interview.
“The findings point to the fact that we still have a high death rate with this disorder, whether directly or indirectly related,” said Dr. Key, the Harold R. Roberts Distinguished Professor and vice chief for research in the division of hematology at the University of North Carolina at Chapel Hill. “[AHA] is still a high-morbidity, high-mortality condition, and these are very high-risk patients.”
The Spanish AHA registry data
The authors retrospectively collected data on 154 patients who were diagnosed with AHA at 36 Spanish hospitals from May 2014 through September 2020 and followed for a median of 12 months.
The patients were mostly men (56.3%) and had a median age of 74 years at diagnosis.
A third were on antithrombotic therapy at diagnosis, and hemostatic treatment was used in 70% of cases.
“Only one patient did not achieve control of hemorrhage. Complete remission (CR) was achieved by 84.2% of cases after immunosuppressive therapy,” the authors wrote, noting that “steroids alone were less efficient than the other strategies (68.2% vs. 87.2%), whereas no differences existed among these (steroids/cyclophosphamide, 88.5%; vs. steroids/calcineurin inhibitors, 81.2%; vs. rituximab-based regimens, 87.5%).
Women and those with high inhibitor levels were less likely to achieve CR, they said.
Of the 154 registry participants, 36 died, and 15 (9.9%) of those died as a result of infection, the leading cause of death. Five (3.3%) died as a result of hemorrhage. All of the hemorrhage-related deaths and half of the infection-related deaths occurred within 2 months of diagnosis, they noted, adding that “prior antithrombotic therapy was inversely associated with survival, irrespective of age.”
The median age of nonsurvivors was significantly higher than that of survivors (79 vs. 73 years), and the median age of those who died from infection was significantly higher than that of patients who died from other causes (85 vs. 78 years).
Additional insights
“One remarkable finding, not described before in AHA, was the high proportion of patients on antithrombotic therapy in the days before AHA diagnosis, namely one-third of the whole series,” the authors wrote. “This proportion is comparable to that of the Spanish population of similar age groups.”
Further, the use of antithrombotic therapy prior to AHA diagnosis was associated with mortality during follow-up in patients aged 75 years and older, they noted.
The older age and comorbidity burden among affected patients underscores their vulnerability and the importance of prompt diagnosis, they added, explaining how misdiagnosis might occur: “Attributing the bleeding episode to a hemostatic imbalance caused by the antithrombotic therapy may entail a risk of misdiagnosis. Frail patients could be admitted to hospital shortly after having been administered anticoagulants. In these cases, misdiagnosis would prevent early [immunosuppressive therapy], and patients could be exposed to potentially life-threatening bleedings.”
Delayed diagnoses have also been described in other registries. For example, in the China Acquired Hemophilia Registry (CARE), nearly half of participants had a delayed diagnosis, and younger patients were more likely than older patients to be referred for consultation, the authors explained.
“Interestingly, antiplatelet therapy has been described to delay AHA diagnosis or lead to misdiagnosis of AHA patients. Furthermore, the underlying diseases that prompted antithrombotic therapy highlight the vulnerability of these patients and could contribute to a negative outcome,” they noted.
Given the high rate of fatal infection in the first months of immunosuppressive therapy in the series, and the association between antithrombotic therapy and mortality, particular care should be taken to avoid misdiagnosis, the authors stressed.
They noted, however, that the study has some important limitations inherent in retrospective analyses and studies with limited sample size and missing data.
Still, the findings add value, they said.
“AHA is not well-known among clinicians unfamiliar with hemostatic disorders. Lack of awareness may preclude early diagnosis, thus exposing patients to an unacceptably high bleeding risk,” they explained, adding that existing management guidelines for the use of immunosuppressive therapy “rely on registry findings and authors’ experience rather than on comparative studies.”
“Therefore, any valuable knowledge regarding clinical experience in managing this disorder should be helpful,” they wrote. “The rarity of the condition prompts the design of registries to compile as much information as possible concerning baseline status, diagnosis, treatment, and follow-up ... to continuously update guidelines on disease management procedures.”
Indeed, the AHASR is “a good-sized registry” and these data are valuable, Dr. Key said.
“I like the fact that they focused on a couple of things here to do with outcomes, particularly analyzing the causes of death,” he said, noting that the reported death is not remarkably different from what has been reported previously, but it does “raise the question of morbidity also related to the therapy – particularly infection.”
The data are especially useful with respect to use of immunosuppressive regimens, he said.
“These are, for the most part, old or frail patients. ... They can’t just be put on cyclophosphamide and sent away without monitoring blood counts and being given advice about what to look out for regarding infection and when to seek treatment,” he said, adding that immunosuppressive regimens are “given for very good and necessary reasons, but are not benign.”
“There ought to be consideration, if necessary, of advice from an infectious disease specialist,” he added, noting that “rheumatologists deal with this all the time, but hematologists often underestimate the infectious morbidity of [immunosuppressive therapy].”
The study authors reported having no conflicts of interest to disclose. Dr. Key has served at the chair of a grant committee for Novo Nordisk.
The findings also indicate that an unusually large proportion of patients were on antithrombotic therapy, which may have led to misdiagnosis or delayed diagnosis of acquired hemophilia A (AHA) in some cases, Marıa-Eva Mingot-Castellano, MD, PhD, of Hospital Universitario Virgen del Rocıo, Seville, Spain, and Hospital Regional Universitario de Malaga (Spain) and colleagues reported on behalf of the Acquired Haemophilia-A Spanish Registry (AHASR).
The report was published online in Blood Advances.
These data provide useful clinical information about a rare disease, and they underscore the need for vigilance when prescribing immunosuppressive therapy for frail, elderly patients with AHA, hematologist Nigel Key, MD, said in an interview.
“The findings point to the fact that we still have a high death rate with this disorder, whether directly or indirectly related,” said Dr. Key, the Harold R. Roberts Distinguished Professor and vice chief for research in the division of hematology at the University of North Carolina at Chapel Hill. “[AHA] is still a high-morbidity, high-mortality condition, and these are very high-risk patients.”
The Spanish AHA registry data
The authors retrospectively collected data on 154 patients who were diagnosed with AHA at 36 Spanish hospitals from May 2014 through September 2020 and followed for a median of 12 months.
The patients were mostly men (56.3%) and had a median age of 74 years at diagnosis.
A third were on antithrombotic therapy at diagnosis, and hemostatic treatment was used in 70% of cases.
“Only one patient did not achieve control of hemorrhage. Complete remission (CR) was achieved by 84.2% of cases after immunosuppressive therapy,” the authors wrote, noting that “steroids alone were less efficient than the other strategies (68.2% vs. 87.2%), whereas no differences existed among these (steroids/cyclophosphamide, 88.5%; vs. steroids/calcineurin inhibitors, 81.2%; vs. rituximab-based regimens, 87.5%).
Women and those with high inhibitor levels were less likely to achieve CR, they said.
Of the 154 registry participants, 36 died, and 15 (9.9%) of those died as a result of infection, the leading cause of death. Five (3.3%) died as a result of hemorrhage. All of the hemorrhage-related deaths and half of the infection-related deaths occurred within 2 months of diagnosis, they noted, adding that “prior antithrombotic therapy was inversely associated with survival, irrespective of age.”
The median age of nonsurvivors was significantly higher than that of survivors (79 vs. 73 years), and the median age of those who died from infection was significantly higher than that of patients who died from other causes (85 vs. 78 years).
Additional insights
“One remarkable finding, not described before in AHA, was the high proportion of patients on antithrombotic therapy in the days before AHA diagnosis, namely one-third of the whole series,” the authors wrote. “This proportion is comparable to that of the Spanish population of similar age groups.”
Further, the use of antithrombotic therapy prior to AHA diagnosis was associated with mortality during follow-up in patients aged 75 years and older, they noted.
The older age and comorbidity burden among affected patients underscores their vulnerability and the importance of prompt diagnosis, they added, explaining how misdiagnosis might occur: “Attributing the bleeding episode to a hemostatic imbalance caused by the antithrombotic therapy may entail a risk of misdiagnosis. Frail patients could be admitted to hospital shortly after having been administered anticoagulants. In these cases, misdiagnosis would prevent early [immunosuppressive therapy], and patients could be exposed to potentially life-threatening bleedings.”
Delayed diagnoses have also been described in other registries. For example, in the China Acquired Hemophilia Registry (CARE), nearly half of participants had a delayed diagnosis, and younger patients were more likely than older patients to be referred for consultation, the authors explained.
“Interestingly, antiplatelet therapy has been described to delay AHA diagnosis or lead to misdiagnosis of AHA patients. Furthermore, the underlying diseases that prompted antithrombotic therapy highlight the vulnerability of these patients and could contribute to a negative outcome,” they noted.
Given the high rate of fatal infection in the first months of immunosuppressive therapy in the series, and the association between antithrombotic therapy and mortality, particular care should be taken to avoid misdiagnosis, the authors stressed.
They noted, however, that the study has some important limitations inherent in retrospective analyses and studies with limited sample size and missing data.
Still, the findings add value, they said.
“AHA is not well-known among clinicians unfamiliar with hemostatic disorders. Lack of awareness may preclude early diagnosis, thus exposing patients to an unacceptably high bleeding risk,” they explained, adding that existing management guidelines for the use of immunosuppressive therapy “rely on registry findings and authors’ experience rather than on comparative studies.”
“Therefore, any valuable knowledge regarding clinical experience in managing this disorder should be helpful,” they wrote. “The rarity of the condition prompts the design of registries to compile as much information as possible concerning baseline status, diagnosis, treatment, and follow-up ... to continuously update guidelines on disease management procedures.”
Indeed, the AHASR is “a good-sized registry” and these data are valuable, Dr. Key said.
“I like the fact that they focused on a couple of things here to do with outcomes, particularly analyzing the causes of death,” he said, noting that the reported death is not remarkably different from what has been reported previously, but it does “raise the question of morbidity also related to the therapy – particularly infection.”
The data are especially useful with respect to use of immunosuppressive regimens, he said.
“These are, for the most part, old or frail patients. ... They can’t just be put on cyclophosphamide and sent away without monitoring blood counts and being given advice about what to look out for regarding infection and when to seek treatment,” he said, adding that immunosuppressive regimens are “given for very good and necessary reasons, but are not benign.”
“There ought to be consideration, if necessary, of advice from an infectious disease specialist,” he added, noting that “rheumatologists deal with this all the time, but hematologists often underestimate the infectious morbidity of [immunosuppressive therapy].”
The study authors reported having no conflicts of interest to disclose. Dr. Key has served at the chair of a grant committee for Novo Nordisk.
The findings also indicate that an unusually large proportion of patients were on antithrombotic therapy, which may have led to misdiagnosis or delayed diagnosis of acquired hemophilia A (AHA) in some cases, Marıa-Eva Mingot-Castellano, MD, PhD, of Hospital Universitario Virgen del Rocıo, Seville, Spain, and Hospital Regional Universitario de Malaga (Spain) and colleagues reported on behalf of the Acquired Haemophilia-A Spanish Registry (AHASR).
The report was published online in Blood Advances.
These data provide useful clinical information about a rare disease, and they underscore the need for vigilance when prescribing immunosuppressive therapy for frail, elderly patients with AHA, hematologist Nigel Key, MD, said in an interview.
“The findings point to the fact that we still have a high death rate with this disorder, whether directly or indirectly related,” said Dr. Key, the Harold R. Roberts Distinguished Professor and vice chief for research in the division of hematology at the University of North Carolina at Chapel Hill. “[AHA] is still a high-morbidity, high-mortality condition, and these are very high-risk patients.”
The Spanish AHA registry data
The authors retrospectively collected data on 154 patients who were diagnosed with AHA at 36 Spanish hospitals from May 2014 through September 2020 and followed for a median of 12 months.
The patients were mostly men (56.3%) and had a median age of 74 years at diagnosis.
A third were on antithrombotic therapy at diagnosis, and hemostatic treatment was used in 70% of cases.
“Only one patient did not achieve control of hemorrhage. Complete remission (CR) was achieved by 84.2% of cases after immunosuppressive therapy,” the authors wrote, noting that “steroids alone were less efficient than the other strategies (68.2% vs. 87.2%), whereas no differences existed among these (steroids/cyclophosphamide, 88.5%; vs. steroids/calcineurin inhibitors, 81.2%; vs. rituximab-based regimens, 87.5%).
Women and those with high inhibitor levels were less likely to achieve CR, they said.
Of the 154 registry participants, 36 died, and 15 (9.9%) of those died as a result of infection, the leading cause of death. Five (3.3%) died as a result of hemorrhage. All of the hemorrhage-related deaths and half of the infection-related deaths occurred within 2 months of diagnosis, they noted, adding that “prior antithrombotic therapy was inversely associated with survival, irrespective of age.”
The median age of nonsurvivors was significantly higher than that of survivors (79 vs. 73 years), and the median age of those who died from infection was significantly higher than that of patients who died from other causes (85 vs. 78 years).
Additional insights
“One remarkable finding, not described before in AHA, was the high proportion of patients on antithrombotic therapy in the days before AHA diagnosis, namely one-third of the whole series,” the authors wrote. “This proportion is comparable to that of the Spanish population of similar age groups.”
Further, the use of antithrombotic therapy prior to AHA diagnosis was associated with mortality during follow-up in patients aged 75 years and older, they noted.
The older age and comorbidity burden among affected patients underscores their vulnerability and the importance of prompt diagnosis, they added, explaining how misdiagnosis might occur: “Attributing the bleeding episode to a hemostatic imbalance caused by the antithrombotic therapy may entail a risk of misdiagnosis. Frail patients could be admitted to hospital shortly after having been administered anticoagulants. In these cases, misdiagnosis would prevent early [immunosuppressive therapy], and patients could be exposed to potentially life-threatening bleedings.”
Delayed diagnoses have also been described in other registries. For example, in the China Acquired Hemophilia Registry (CARE), nearly half of participants had a delayed diagnosis, and younger patients were more likely than older patients to be referred for consultation, the authors explained.
“Interestingly, antiplatelet therapy has been described to delay AHA diagnosis or lead to misdiagnosis of AHA patients. Furthermore, the underlying diseases that prompted antithrombotic therapy highlight the vulnerability of these patients and could contribute to a negative outcome,” they noted.
Given the high rate of fatal infection in the first months of immunosuppressive therapy in the series, and the association between antithrombotic therapy and mortality, particular care should be taken to avoid misdiagnosis, the authors stressed.
They noted, however, that the study has some important limitations inherent in retrospective analyses and studies with limited sample size and missing data.
Still, the findings add value, they said.
“AHA is not well-known among clinicians unfamiliar with hemostatic disorders. Lack of awareness may preclude early diagnosis, thus exposing patients to an unacceptably high bleeding risk,” they explained, adding that existing management guidelines for the use of immunosuppressive therapy “rely on registry findings and authors’ experience rather than on comparative studies.”
“Therefore, any valuable knowledge regarding clinical experience in managing this disorder should be helpful,” they wrote. “The rarity of the condition prompts the design of registries to compile as much information as possible concerning baseline status, diagnosis, treatment, and follow-up ... to continuously update guidelines on disease management procedures.”
Indeed, the AHASR is “a good-sized registry” and these data are valuable, Dr. Key said.
“I like the fact that they focused on a couple of things here to do with outcomes, particularly analyzing the causes of death,” he said, noting that the reported death is not remarkably different from what has been reported previously, but it does “raise the question of morbidity also related to the therapy – particularly infection.”
The data are especially useful with respect to use of immunosuppressive regimens, he said.
“These are, for the most part, old or frail patients. ... They can’t just be put on cyclophosphamide and sent away without monitoring blood counts and being given advice about what to look out for regarding infection and when to seek treatment,” he said, adding that immunosuppressive regimens are “given for very good and necessary reasons, but are not benign.”
“There ought to be consideration, if necessary, of advice from an infectious disease specialist,” he added, noting that “rheumatologists deal with this all the time, but hematologists often underestimate the infectious morbidity of [immunosuppressive therapy].”
The study authors reported having no conflicts of interest to disclose. Dr. Key has served at the chair of a grant committee for Novo Nordisk.
FROM BLOOD ADVANCES
CAR T for ALL: Areas that need optimizing
The success of chimeric antigen receptor T (CAR T)-cell therapy for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) has garnered much attention, but the field is still in its infancy – with toxicity and relapse rates remaining unacceptably high.
in the use of the therapy in this setting, according to review authors Vanessa A. Fabrizio, MD, a fellow at Duke University, Durham, N.C., and Kevin J. Curran, MD, a pediatric oncologist at Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York.
Based on their review of early pivotal clinical trials, relapse data, toxicities, and mechanisms to optimize CAR T-cell therapy, Dr. Fabrizio and Dr. Curran outlined several “practice points” and proposed a research agenda aimed at optimizing the use of CAR T-cell therapy for B-ALL (Best Pract Res Clin Haematol. 2021 Aug 27. doi: 10.1016/j.beha.2021.101305).
Practice points
CAR T-cell therapy has transformed the treatment of both pediatric and adult patients with relapsed/refractory (R/R) B-ALL, the authors said, adding that “[c]linical trial results across multiple institutions with different CAR constructs report significant response rates in treated patients.”
Dr. Fabrizio and Dr. Curran specifically note that only one product (tisagenlecleucel) is currently approved for the treatment of R/R B-ALL in patients under age 26 years. Further, the successful application of this therapy is limited by high relapse rates, significant toxicity in some cases, and challenges related to collection and production issues.
They contend that areas in which optimization of CAR T-cell therapy can occur include apheresis, production, chemotherapy bridging, pretreatment disease burden management, toxicity management, disease monitoring after therapy, and use of consolidative allogeneic hematopoietic stem cell transplantation.
Research agenda
Key ways to heighten the success of CAR T-cell therapy for B-ALL are the development of off-the-shelf CAR T-cell products and the selection of optimal T cells to enhance apheresis and production, they said, adding that research is needed on the use of bridging chemotherapy to reduce tumor burden.
Bridging chemotherapy has been shown to impact outcomes while minimizing toxicity, but it remains undefined.
“Prospective trials are required to determine if the optimization of lymphodepleting chemotherapy can improve outcomes, and if consolidative therapy with transplantation should be considered in select patients,” they wrote. “Continued efforts to improve this technology for patients is ongoing while remaining questions are being investigated.”
The authors acknowledge that CAR T-cell therapy has transformed the treatment landscape for both pediatric and adult patients with R/R B-ALL, but this extensive review of all published data on the subject shows that “the incidence of relapse among responders is unacceptably high, demonstrating the need to improve this therapy.”
In conclusion, they wrote: “To be effective following infusion, CAR T cells must expand, persist, exhibit enduring anti-tumor cytotoxicity, withstand and/or counteract an immunosuppressive tumor microenvironment, and overcome targeted tumor antigen escape. In designing CAR T cells for cancer immunotherapy, all of these factors must be harmonized to generate the optimal therapy,” noting that “[t]oxicity management and, ideally the prediction of toxicity in individualized patients, should continue to be a focus of ongoing efforts.”
Dr. Curran has received research support from Juno Therapeutics and Novartis, and has consulted, participated in advisory boards, or taken part in educational seminars for Juno Therapeutics, Novartis, and Mesoblast. Dr. Fabrizio reported having no conflict of interests.
The success of chimeric antigen receptor T (CAR T)-cell therapy for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) has garnered much attention, but the field is still in its infancy – with toxicity and relapse rates remaining unacceptably high.
in the use of the therapy in this setting, according to review authors Vanessa A. Fabrizio, MD, a fellow at Duke University, Durham, N.C., and Kevin J. Curran, MD, a pediatric oncologist at Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York.
Based on their review of early pivotal clinical trials, relapse data, toxicities, and mechanisms to optimize CAR T-cell therapy, Dr. Fabrizio and Dr. Curran outlined several “practice points” and proposed a research agenda aimed at optimizing the use of CAR T-cell therapy for B-ALL (Best Pract Res Clin Haematol. 2021 Aug 27. doi: 10.1016/j.beha.2021.101305).
Practice points
CAR T-cell therapy has transformed the treatment of both pediatric and adult patients with relapsed/refractory (R/R) B-ALL, the authors said, adding that “[c]linical trial results across multiple institutions with different CAR constructs report significant response rates in treated patients.”
Dr. Fabrizio and Dr. Curran specifically note that only one product (tisagenlecleucel) is currently approved for the treatment of R/R B-ALL in patients under age 26 years. Further, the successful application of this therapy is limited by high relapse rates, significant toxicity in some cases, and challenges related to collection and production issues.
They contend that areas in which optimization of CAR T-cell therapy can occur include apheresis, production, chemotherapy bridging, pretreatment disease burden management, toxicity management, disease monitoring after therapy, and use of consolidative allogeneic hematopoietic stem cell transplantation.
Research agenda
Key ways to heighten the success of CAR T-cell therapy for B-ALL are the development of off-the-shelf CAR T-cell products and the selection of optimal T cells to enhance apheresis and production, they said, adding that research is needed on the use of bridging chemotherapy to reduce tumor burden.
Bridging chemotherapy has been shown to impact outcomes while minimizing toxicity, but it remains undefined.
“Prospective trials are required to determine if the optimization of lymphodepleting chemotherapy can improve outcomes, and if consolidative therapy with transplantation should be considered in select patients,” they wrote. “Continued efforts to improve this technology for patients is ongoing while remaining questions are being investigated.”
The authors acknowledge that CAR T-cell therapy has transformed the treatment landscape for both pediatric and adult patients with R/R B-ALL, but this extensive review of all published data on the subject shows that “the incidence of relapse among responders is unacceptably high, demonstrating the need to improve this therapy.”
In conclusion, they wrote: “To be effective following infusion, CAR T cells must expand, persist, exhibit enduring anti-tumor cytotoxicity, withstand and/or counteract an immunosuppressive tumor microenvironment, and overcome targeted tumor antigen escape. In designing CAR T cells for cancer immunotherapy, all of these factors must be harmonized to generate the optimal therapy,” noting that “[t]oxicity management and, ideally the prediction of toxicity in individualized patients, should continue to be a focus of ongoing efforts.”
Dr. Curran has received research support from Juno Therapeutics and Novartis, and has consulted, participated in advisory boards, or taken part in educational seminars for Juno Therapeutics, Novartis, and Mesoblast. Dr. Fabrizio reported having no conflict of interests.
The success of chimeric antigen receptor T (CAR T)-cell therapy for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) has garnered much attention, but the field is still in its infancy – with toxicity and relapse rates remaining unacceptably high.
in the use of the therapy in this setting, according to review authors Vanessa A. Fabrizio, MD, a fellow at Duke University, Durham, N.C., and Kevin J. Curran, MD, a pediatric oncologist at Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York.
Based on their review of early pivotal clinical trials, relapse data, toxicities, and mechanisms to optimize CAR T-cell therapy, Dr. Fabrizio and Dr. Curran outlined several “practice points” and proposed a research agenda aimed at optimizing the use of CAR T-cell therapy for B-ALL (Best Pract Res Clin Haematol. 2021 Aug 27. doi: 10.1016/j.beha.2021.101305).
Practice points
CAR T-cell therapy has transformed the treatment of both pediatric and adult patients with relapsed/refractory (R/R) B-ALL, the authors said, adding that “[c]linical trial results across multiple institutions with different CAR constructs report significant response rates in treated patients.”
Dr. Fabrizio and Dr. Curran specifically note that only one product (tisagenlecleucel) is currently approved for the treatment of R/R B-ALL in patients under age 26 years. Further, the successful application of this therapy is limited by high relapse rates, significant toxicity in some cases, and challenges related to collection and production issues.
They contend that areas in which optimization of CAR T-cell therapy can occur include apheresis, production, chemotherapy bridging, pretreatment disease burden management, toxicity management, disease monitoring after therapy, and use of consolidative allogeneic hematopoietic stem cell transplantation.
Research agenda
Key ways to heighten the success of CAR T-cell therapy for B-ALL are the development of off-the-shelf CAR T-cell products and the selection of optimal T cells to enhance apheresis and production, they said, adding that research is needed on the use of bridging chemotherapy to reduce tumor burden.
Bridging chemotherapy has been shown to impact outcomes while minimizing toxicity, but it remains undefined.
“Prospective trials are required to determine if the optimization of lymphodepleting chemotherapy can improve outcomes, and if consolidative therapy with transplantation should be considered in select patients,” they wrote. “Continued efforts to improve this technology for patients is ongoing while remaining questions are being investigated.”
The authors acknowledge that CAR T-cell therapy has transformed the treatment landscape for both pediatric and adult patients with R/R B-ALL, but this extensive review of all published data on the subject shows that “the incidence of relapse among responders is unacceptably high, demonstrating the need to improve this therapy.”
In conclusion, they wrote: “To be effective following infusion, CAR T cells must expand, persist, exhibit enduring anti-tumor cytotoxicity, withstand and/or counteract an immunosuppressive tumor microenvironment, and overcome targeted tumor antigen escape. In designing CAR T cells for cancer immunotherapy, all of these factors must be harmonized to generate the optimal therapy,” noting that “[t]oxicity management and, ideally the prediction of toxicity in individualized patients, should continue to be a focus of ongoing efforts.”
Dr. Curran has received research support from Juno Therapeutics and Novartis, and has consulted, participated in advisory boards, or taken part in educational seminars for Juno Therapeutics, Novartis, and Mesoblast. Dr. Fabrizio reported having no conflict of interests.
FROM BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY