AVAHO

An analysis of 61 cities in the United States where employers allow paid work absences for preventive medical services, such as breast and colon cancer screenings, shows that having the option of paid leave does in fact influence one’s decision to have preventive cancer screenings.

“Our results provide evidence for policymakers considering legislative or regulatory solutions to address insufficient screening adherence and highlight an understudied benefit of expanding paid sick leave coverage,” wrote authors who were led by Kevin Callison, PhD, of the Tulane University School of Public Health and Tropical Medicine, New Orleans.

The findings were published earlier this year in the New England Journal of Medicine.

Despite an Affordable Care Act provision eliminating most cost-sharing for cancer screening, the rate for recommended breast and colorectal cancer screening among U.S. adults is lower than 70%. Work commitments, time constraints, and the prospect of lost wages are frequently cited as contributing factors to this underuse of preventive care. Researchers hypothesized that having paid sick leave coverage for the use of preventive services could improve adherence to cancer screening guidelines. With continued failure to pass a bill mandating federal paid sick leave legislation, nearly 30% of the nation’s workforce lacks this coverage. Rates are lower for low-income workers, women, and underserved racial and ethnic groups, the authors write.

Coverage mandates have become politically contentious, as evidenced by the fact that their passage by some states (n = 17), counties (n = 4) and cities (n = 18) has been met by many states (n = 18) passing preemption laws banning municipalities from adopting the laws.

In this study, researchers examined the rate of colorectal and breast cancer screening at 12- and 24-month intervals among people living in one of 61 cities. Before paid sick leave mandates were put in place, cancer screening rates were similar across the board. But once mandates were put in place, cancer screening rates were higher among workers affected by the mandate by 1.31% (95% confidence interval, 0.28-2.34) for 12-month colorectal cancer screening, 1.56% (95% CI, 0.33-2.79) for 24-month colorectal cancer screening, 1.22% (95% CI, −0.20 to 2.64) for 12-month mammography, and 2.07% (95% CI, 0.15-3.99) for 24-month mammography.

“Although these appear to be modest effects, spread across a large population, these indicate a fairly substantial gain in cancer screenings,” Dr. Callison said.

Prior studies showing positive associations between having paid sick leave coverage and whether someone receives cancer screenings are likely confounded by selection bias because they compare workers who have such coverage to those who do not, Dr. Callison and colleagues state in their paper.

“Although the lack of paid sick leave coverage may hinder access to preventive care, current evidence is insufficient to draw meaningful conclusions about its relationship to cancer screening,” the authors write, citing that particularly health conscious workers may take jobs offering sick leave coverage.

Through quasi-experimental design, the present study aimed to overcome such confounding issues. Its analytic sample, using administrative data from the Merative MarketScan Research Databases, encompassed approximately 2.5 million person-specific records per year for the colorectal cancer screening sample. The researchers’ mammography sample included 1.3 million person-specific records per year of the period examined.

The associations cited above translate into relative colorectal cancer screening increases of 8.1% in the 12-month adjusted model and a 5.9% relative increase from the premandate rate in the 24-month adjusted model. The rate was 1.56 percentage points (95% CI, 0.33-2.79) higher in the cities subject to the paid sick leave mandates (a 5.9% relative increase from the premandate rate). For screening mammography in the cities subject to the mandates, the 12-month adjusted 1.22% increase (95% CI, –0.20 to 2.64) represented a 2.5% relative increase from the premandate level. The adjusted 24-month rate increase of 2.07% (95% CI, 0.15-4.00) represented a 3.3% relative increase from premandate rates.

“However, these estimates are averages across all workers in our sample, many of whom likely already had paid sick leave coverage prior to the enactment of a mandate,” Dr. Callison said in the interview. “In fact, in other work related to this project, we estimated that about 28% of private sector workers gain paid sick leave when a mandate is enacted. So then, if we scale our findings by the share of workers actually gaining paid sick leave coverage, our estimates are much larger – a 9%-12% increase in screening mammography and a 21%-29% increase in colorectal cancer screening.”

Dr. Callison and his team are in the process of developing a follow-up proposal that would examine the effects of paid sick leave on downstream outcomes of the cancer care continuum, such as timing from diagnosis to treatment initiation. “We also hope to examine who benefits from these additional screens and what they mean for health equity. Data limitations prevented us from exploring that issue in the current study,” he said.

Dr. Callison had no conflicts associated with this study.

An analysis of 61 cities in the United States where employers allow paid work absences for preventive medical services, such as breast and colon cancer screenings, shows that having the option of paid leave does in fact influence one’s decision to have preventive cancer screenings.

“Our results provide evidence for policymakers considering legislative or regulatory solutions to address insufficient screening adherence and highlight an understudied benefit of expanding paid sick leave coverage,” wrote authors who were led by Kevin Callison, PhD, of the Tulane University School of Public Health and Tropical Medicine, New Orleans.

The findings were published earlier this year in the New England Journal of Medicine.

Despite an Affordable Care Act provision eliminating most cost-sharing for cancer screening, the rate for recommended breast and colorectal cancer screening among U.S. adults is lower than 70%. Work commitments, time constraints, and the prospect of lost wages are frequently cited as contributing factors to this underuse of preventive care. Researchers hypothesized that having paid sick leave coverage for the use of preventive services could improve adherence to cancer screening guidelines. With continued failure to pass a bill mandating federal paid sick leave legislation, nearly 30% of the nation’s workforce lacks this coverage. Rates are lower for low-income workers, women, and underserved racial and ethnic groups, the authors write.

Coverage mandates have become politically contentious, as evidenced by the fact that their passage by some states (n = 17), counties (n = 4) and cities (n = 18) has been met by many states (n = 18) passing preemption laws banning municipalities from adopting the laws.

In this study, researchers examined the rate of colorectal and breast cancer screening at 12- and 24-month intervals among people living in one of 61 cities. Before paid sick leave mandates were put in place, cancer screening rates were similar across the board. But once mandates were put in place, cancer screening rates were higher among workers affected by the mandate by 1.31% (95% confidence interval, 0.28-2.34) for 12-month colorectal cancer screening, 1.56% (95% CI, 0.33-2.79) for 24-month colorectal cancer screening, 1.22% (95% CI, −0.20 to 2.64) for 12-month mammography, and 2.07% (95% CI, 0.15-3.99) for 24-month mammography.

“Although these appear to be modest effects, spread across a large population, these indicate a fairly substantial gain in cancer screenings,” Dr. Callison said.

Prior studies showing positive associations between having paid sick leave coverage and whether someone receives cancer screenings are likely confounded by selection bias because they compare workers who have such coverage to those who do not, Dr. Callison and colleagues state in their paper.

“Although the lack of paid sick leave coverage may hinder access to preventive care, current evidence is insufficient to draw meaningful conclusions about its relationship to cancer screening,” the authors write, citing that particularly health conscious workers may take jobs offering sick leave coverage.

Through quasi-experimental design, the present study aimed to overcome such confounding issues. Its analytic sample, using administrative data from the Merative MarketScan Research Databases, encompassed approximately 2.5 million person-specific records per year for the colorectal cancer screening sample. The researchers’ mammography sample included 1.3 million person-specific records per year of the period examined.

The associations cited above translate into relative colorectal cancer screening increases of 8.1% in the 12-month adjusted model and a 5.9% relative increase from the premandate rate in the 24-month adjusted model. The rate was 1.56 percentage points (95% CI, 0.33-2.79) higher in the cities subject to the paid sick leave mandates (a 5.9% relative increase from the premandate rate). For screening mammography in the cities subject to the mandates, the 12-month adjusted 1.22% increase (95% CI, –0.20 to 2.64) represented a 2.5% relative increase from the premandate level. The adjusted 24-month rate increase of 2.07% (95% CI, 0.15-4.00) represented a 3.3% relative increase from premandate rates.

“However, these estimates are averages across all workers in our sample, many of whom likely already had paid sick leave coverage prior to the enactment of a mandate,” Dr. Callison said in the interview. “In fact, in other work related to this project, we estimated that about 28% of private sector workers gain paid sick leave when a mandate is enacted. So then, if we scale our findings by the share of workers actually gaining paid sick leave coverage, our estimates are much larger – a 9%-12% increase in screening mammography and a 21%-29% increase in colorectal cancer screening.”

Dr. Callison and his team are in the process of developing a follow-up proposal that would examine the effects of paid sick leave on downstream outcomes of the cancer care continuum, such as timing from diagnosis to treatment initiation. “We also hope to examine who benefits from these additional screens and what they mean for health equity. Data limitations prevented us from exploring that issue in the current study,” he said.

Dr. Callison had no conflicts associated with this study.

An analysis of 61 cities in the United States where employers allow paid work absences for preventive medical services, such as breast and colon cancer screenings, shows that having the option of paid leave does in fact influence one’s decision to have preventive cancer screenings.

“Our results provide evidence for policymakers considering legislative or regulatory solutions to address insufficient screening adherence and highlight an understudied benefit of expanding paid sick leave coverage,” wrote authors who were led by Kevin Callison, PhD, of the Tulane University School of Public Health and Tropical Medicine, New Orleans.

The findings were published earlier this year in the New England Journal of Medicine.

Despite an Affordable Care Act provision eliminating most cost-sharing for cancer screening, the rate for recommended breast and colorectal cancer screening among U.S. adults is lower than 70%. Work commitments, time constraints, and the prospect of lost wages are frequently cited as contributing factors to this underuse of preventive care. Researchers hypothesized that having paid sick leave coverage for the use of preventive services could improve adherence to cancer screening guidelines. With continued failure to pass a bill mandating federal paid sick leave legislation, nearly 30% of the nation’s workforce lacks this coverage. Rates are lower for low-income workers, women, and underserved racial and ethnic groups, the authors write.

Coverage mandates have become politically contentious, as evidenced by the fact that their passage by some states (n = 17), counties (n = 4) and cities (n = 18) has been met by many states (n = 18) passing preemption laws banning municipalities from adopting the laws.

In this study, researchers examined the rate of colorectal and breast cancer screening at 12- and 24-month intervals among people living in one of 61 cities. Before paid sick leave mandates were put in place, cancer screening rates were similar across the board. But once mandates were put in place, cancer screening rates were higher among workers affected by the mandate by 1.31% (95% confidence interval, 0.28-2.34) for 12-month colorectal cancer screening, 1.56% (95% CI, 0.33-2.79) for 24-month colorectal cancer screening, 1.22% (95% CI, −0.20 to 2.64) for 12-month mammography, and 2.07% (95% CI, 0.15-3.99) for 24-month mammography.

“Although these appear to be modest effects, spread across a large population, these indicate a fairly substantial gain in cancer screenings,” Dr. Callison said.

Prior studies showing positive associations between having paid sick leave coverage and whether someone receives cancer screenings are likely confounded by selection bias because they compare workers who have such coverage to those who do not, Dr. Callison and colleagues state in their paper.

“Although the lack of paid sick leave coverage may hinder access to preventive care, current evidence is insufficient to draw meaningful conclusions about its relationship to cancer screening,” the authors write, citing that particularly health conscious workers may take jobs offering sick leave coverage.

Through quasi-experimental design, the present study aimed to overcome such confounding issues. Its analytic sample, using administrative data from the Merative MarketScan Research Databases, encompassed approximately 2.5 million person-specific records per year for the colorectal cancer screening sample. The researchers’ mammography sample included 1.3 million person-specific records per year of the period examined.

The associations cited above translate into relative colorectal cancer screening increases of 8.1% in the 12-month adjusted model and a 5.9% relative increase from the premandate rate in the 24-month adjusted model. The rate was 1.56 percentage points (95% CI, 0.33-2.79) higher in the cities subject to the paid sick leave mandates (a 5.9% relative increase from the premandate rate). For screening mammography in the cities subject to the mandates, the 12-month adjusted 1.22% increase (95% CI, –0.20 to 2.64) represented a 2.5% relative increase from the premandate level. The adjusted 24-month rate increase of 2.07% (95% CI, 0.15-4.00) represented a 3.3% relative increase from premandate rates.

“However, these estimates are averages across all workers in our sample, many of whom likely already had paid sick leave coverage prior to the enactment of a mandate,” Dr. Callison said in the interview. “In fact, in other work related to this project, we estimated that about 28% of private sector workers gain paid sick leave when a mandate is enacted. So then, if we scale our findings by the share of workers actually gaining paid sick leave coverage, our estimates are much larger – a 9%-12% increase in screening mammography and a 21%-29% increase in colorectal cancer screening.”

Dr. Callison and his team are in the process of developing a follow-up proposal that would examine the effects of paid sick leave on downstream outcomes of the cancer care continuum, such as timing from diagnosis to treatment initiation. “We also hope to examine who benefits from these additional screens and what they mean for health equity. Data limitations prevented us from exploring that issue in the current study,” he said.

Dr. Callison had no conflicts associated with this study.

CHICAGO – The regular use of aspirin or other nonsteroidal anti-inflammatory drugs was found to be associated with a lower risk of early-onset conventional and advanced adenomas. The authors say that aspirin could prove to be an effective strategy in preventing early-onset colorectal cancer cases.

“What we have here is a 15% reduction for all adenomas and 33% for those with advanced histology, which to us is quite substantial. We have not seen that much [33%] in previous studies so I would think it definitely needs more study,” said Cassandra D. Fritz, MD, MPHS, a gastroenterologist with Washington University, St. Louis, in an oral presentation given at the annual Digestive Disease Week^®.

“This finding is important given the alarming rise in the incidence and mortality of early-onset colorectal cancer (age < 50 years), and our limited understanding of the underlying drivers to direct prevention efforts,” Dr. Fritz said. Early-onset colorectal cancer cases have doubled since 1995, she said.

The study confirms evidence from 30 years of research that suggests regular aspirin use reduces cancer risk. In patients with Lynch syndrome, the CAPP2 study showed that aspirin has a protective effect against colorectal cancer at 20 years follow-up.

While emerging data have suggested that aspirin use may reduce later-onset colorectal cancer, it was not known if regular aspirin and NSAID use are associated with diminished risk of early-onset conventional adenomas, and especially the high-risk adenomas conferring greater malignant potential known to be the major precursor of early-onset colorectal cancer. An unpublished analysis of molecular markers by the study’s senior author, Yin Cao, ScD, MPH, also of Washington University, found that at least 57% of early-onset colorectal cancers developed from the conventional adenoma-carcinoma pathway.

The objective of the new study was to assess the association between regular aspirin or NSAID use at least twice weekly, with the risk of developing early-onset adenoma. The analysis is based on an evaluation of data from the Nurses’ Health Study II of 32,058 women who had at least one colonoscopy before age 50 (1991-2015). High-risk adenomas included those that were at least 1 cm with tubulovillous/villous histology or high-grade dysplasia, or the presence of at least three adenomas.

There were 1,247 early-onset adenomas, among which 290 were considered high risk. The risk of adenomas among patients who took aspirin or NSAIDs regularly for cardiovascular protection or for inflammatory conditions, was lower than in those who did not take aspirin and/or NSAIDs regularly. While the association was similar for high-risk vs. low-risk adenomas, the benefit was more pronounced for adenomas of tubulovillous/villous histology or with high-grade dysplasia (odds ratio, 0.67; 95% confidence interval, 0.51-0.89), a 33% reduction, compared with tubular adenomas (OR, 0.90; 95% CI, 0.79-1.0; P for heterogeneity = .02).

With later-onset adenomas, risk reduction was confined primarily to large (OR, 0.76; 95% CI, 0.62-0.93) or multiple adenomas (OR, 0.57; 95% CI, 0.40-0.83), but not adenomas of advanced histology (OR, 0.92; 95% CI, 0.73-1.17).

“With colorectal cancer rates increasing, we still don’t have any preventative strategies beyond screening. With this 15% reduction with aspirin/NSAIDS in early-onset adenoma – and particularly for the quite substantial 33% benefit in advanced adenoma with advanced histology, we need to think about a precision-based chemoprevention strategy for early-onset precursors of colorectal cancer,” Dr. Cao said.

The U.S. Preventive Services Task Force issued a new recommendation in 2021 stating that colorectal cancer screening for people with average risk should start 5 years sooner at age 45. “As we know,” Dr. Yin said, “many younger adults are not screened. That’s why we’re looking into potential early-onset colorectal cancer chemopreventative agents.”

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Dr. Fritz had no disclosures and Dr. Cao listed consulting for Geneoscopy.

CHICAGO – The regular use of aspirin or other nonsteroidal anti-inflammatory drugs was found to be associated with a lower risk of early-onset conventional and advanced adenomas. The authors say that aspirin could prove to be an effective strategy in preventing early-onset colorectal cancer cases.

“What we have here is a 15% reduction for all adenomas and 33% for those with advanced histology, which to us is quite substantial. We have not seen that much [33%] in previous studies so I would think it definitely needs more study,” said Cassandra D. Fritz, MD, MPHS, a gastroenterologist with Washington University, St. Louis, in an oral presentation given at the annual Digestive Disease Week^®.

“This finding is important given the alarming rise in the incidence and mortality of early-onset colorectal cancer (age < 50 years), and our limited understanding of the underlying drivers to direct prevention efforts,” Dr. Fritz said. Early-onset colorectal cancer cases have doubled since 1995, she said.

The study confirms evidence from 30 years of research that suggests regular aspirin use reduces cancer risk. In patients with Lynch syndrome, the CAPP2 study showed that aspirin has a protective effect against colorectal cancer at 20 years follow-up.

While emerging data have suggested that aspirin use may reduce later-onset colorectal cancer, it was not known if regular aspirin and NSAID use are associated with diminished risk of early-onset conventional adenomas, and especially the high-risk adenomas conferring greater malignant potential known to be the major precursor of early-onset colorectal cancer. An unpublished analysis of molecular markers by the study’s senior author, Yin Cao, ScD, MPH, also of Washington University, found that at least 57% of early-onset colorectal cancers developed from the conventional adenoma-carcinoma pathway.

The objective of the new study was to assess the association between regular aspirin or NSAID use at least twice weekly, with the risk of developing early-onset adenoma. The analysis is based on an evaluation of data from the Nurses’ Health Study II of 32,058 women who had at least one colonoscopy before age 50 (1991-2015). High-risk adenomas included those that were at least 1 cm with tubulovillous/villous histology or high-grade dysplasia, or the presence of at least three adenomas.

There were 1,247 early-onset adenomas, among which 290 were considered high risk. The risk of adenomas among patients who took aspirin or NSAIDs regularly for cardiovascular protection or for inflammatory conditions, was lower than in those who did not take aspirin and/or NSAIDs regularly. While the association was similar for high-risk vs. low-risk adenomas, the benefit was more pronounced for adenomas of tubulovillous/villous histology or with high-grade dysplasia (odds ratio, 0.67; 95% confidence interval, 0.51-0.89), a 33% reduction, compared with tubular adenomas (OR, 0.90; 95% CI, 0.79-1.0; P for heterogeneity = .02).

With later-onset adenomas, risk reduction was confined primarily to large (OR, 0.76; 95% CI, 0.62-0.93) or multiple adenomas (OR, 0.57; 95% CI, 0.40-0.83), but not adenomas of advanced histology (OR, 0.92; 95% CI, 0.73-1.17).

“With colorectal cancer rates increasing, we still don’t have any preventative strategies beyond screening. With this 15% reduction with aspirin/NSAIDS in early-onset adenoma – and particularly for the quite substantial 33% benefit in advanced adenoma with advanced histology, we need to think about a precision-based chemoprevention strategy for early-onset precursors of colorectal cancer,” Dr. Cao said.

The U.S. Preventive Services Task Force issued a new recommendation in 2021 stating that colorectal cancer screening for people with average risk should start 5 years sooner at age 45. “As we know,” Dr. Yin said, “many younger adults are not screened. That’s why we’re looking into potential early-onset colorectal cancer chemopreventative agents.”

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Dr. Fritz had no disclosures and Dr. Cao listed consulting for Geneoscopy.

CHICAGO – The regular use of aspirin or other nonsteroidal anti-inflammatory drugs was found to be associated with a lower risk of early-onset conventional and advanced adenomas. The authors say that aspirin could prove to be an effective strategy in preventing early-onset colorectal cancer cases.

“What we have here is a 15% reduction for all adenomas and 33% for those with advanced histology, which to us is quite substantial. We have not seen that much [33%] in previous studies so I would think it definitely needs more study,” said Cassandra D. Fritz, MD, MPHS, a gastroenterologist with Washington University, St. Louis, in an oral presentation given at the annual Digestive Disease Week^®.

“This finding is important given the alarming rise in the incidence and mortality of early-onset colorectal cancer (age < 50 years), and our limited understanding of the underlying drivers to direct prevention efforts,” Dr. Fritz said. Early-onset colorectal cancer cases have doubled since 1995, she said.

The study confirms evidence from 30 years of research that suggests regular aspirin use reduces cancer risk. In patients with Lynch syndrome, the CAPP2 study showed that aspirin has a protective effect against colorectal cancer at 20 years follow-up.

While emerging data have suggested that aspirin use may reduce later-onset colorectal cancer, it was not known if regular aspirin and NSAID use are associated with diminished risk of early-onset conventional adenomas, and especially the high-risk adenomas conferring greater malignant potential known to be the major precursor of early-onset colorectal cancer. An unpublished analysis of molecular markers by the study’s senior author, Yin Cao, ScD, MPH, also of Washington University, found that at least 57% of early-onset colorectal cancers developed from the conventional adenoma-carcinoma pathway.

The objective of the new study was to assess the association between regular aspirin or NSAID use at least twice weekly, with the risk of developing early-onset adenoma. The analysis is based on an evaluation of data from the Nurses’ Health Study II of 32,058 women who had at least one colonoscopy before age 50 (1991-2015). High-risk adenomas included those that were at least 1 cm with tubulovillous/villous histology or high-grade dysplasia, or the presence of at least three adenomas.

There were 1,247 early-onset adenomas, among which 290 were considered high risk. The risk of adenomas among patients who took aspirin or NSAIDs regularly for cardiovascular protection or for inflammatory conditions, was lower than in those who did not take aspirin and/or NSAIDs regularly. While the association was similar for high-risk vs. low-risk adenomas, the benefit was more pronounced for adenomas of tubulovillous/villous histology or with high-grade dysplasia (odds ratio, 0.67; 95% confidence interval, 0.51-0.89), a 33% reduction, compared with tubular adenomas (OR, 0.90; 95% CI, 0.79-1.0; P for heterogeneity = .02).

With later-onset adenomas, risk reduction was confined primarily to large (OR, 0.76; 95% CI, 0.62-0.93) or multiple adenomas (OR, 0.57; 95% CI, 0.40-0.83), but not adenomas of advanced histology (OR, 0.92; 95% CI, 0.73-1.17).

“With colorectal cancer rates increasing, we still don’t have any preventative strategies beyond screening. With this 15% reduction with aspirin/NSAIDS in early-onset adenoma – and particularly for the quite substantial 33% benefit in advanced adenoma with advanced histology, we need to think about a precision-based chemoprevention strategy for early-onset precursors of colorectal cancer,” Dr. Cao said.

The U.S. Preventive Services Task Force issued a new recommendation in 2021 stating that colorectal cancer screening for people with average risk should start 5 years sooner at age 45. “As we know,” Dr. Yin said, “many younger adults are not screened. That’s why we’re looking into potential early-onset colorectal cancer chemopreventative agents.”

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Dr. Fritz had no disclosures and Dr. Cao listed consulting for Geneoscopy.

The first-in-class erythroid maturation agent luspatercept showed significant improvement over the erythropoiesis-stimulating agent epoetin alfa in reducing dependency on red blood cell transfusions among patients with lower-risk myelodysplastic syndromes (LR-MDS) who are ESA naive.

“Luspatercept is the first and only therapy to demonstrate superiority in a head-to-head study against ESAs in [transfusion-dependent] LR-MDS,” first author Guillermo Garcia-Manero, MD, chief of the MDS section, department of leukemia, at the University of Texas MD Anderson Cancer Center, Houston, said in a premeeting press briefing in advance of the annual meeting of the American Society of Clinical Oncology.

“It should be considered a paradigm shift in the treatment of LR-MDS–associated anemia,” Dr. Garcia-Manero said.

Commenting on the study, Andrew Artz, MD, a professor at the Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, Calif., agreed that the results could be practice changing.

“We biologically expected luspatercept to best ESA [in ring sideroblast transfusion–dependent MDS], based on luspatercept often rescuing ESA failures in this setting,” Dr. Artz said in an interview.

“The results have the potential to change initial therapy for patients with low-risk red blood cell transfusion-dependent MDS,” he said.

In LR-MDS, which encompasses a variety of bone marrow disorders, chronic anemia is very common, and patients, who are typically elderly, can become burdened by developing dependencies on RBC transfusions.

Transfusion dependency, in addition to creating a host of challenges, can increase the risk of death by as much as 50%, compared with patients who are not transfusion dependent, Dr. Garcia-Manero noted.

While ESAs such as epoetin alfa are the first-line treatment for LR-MDS, patients who are dependent on transfusions are less likely to respond to the agents, hence “there is an unmet need for effective and durable options other than ESAs for treating anemia in patients with LR-MDS,” Dr. Garcia-Manero said.

Luspatercept, a first-in-class monoclonal antibody, has a mechanism of action that is distinct from ESAs, modulating the transforming growth factor–beta pathway and increasing erythrocytosis.

In the previous phase 3 MEDALIST trial, the drug was shown to have efficacy over placebo in reducing the severity of anemia in LR-MDS. In 2020, in what was deemed the first advance in MDS treatment in more than a decade, those results led to approval by the Food and Drug Administration for patients with LR-MDS with ring sideroblasts who are transfusion dependent and are refractory, intolerant, or ineligible to receive ESAs.

To further investigate luspatercept’s efficacy in a head-to-head comparison with an ESA in LR-MDS patients who are ESA naive, Dr. Garcia-Manero and colleagues conducted the phase 3 COMMANDS trial.

For the global, open-label study, patients with LR-MDS who were dependent on RBC transfusions and had no prior use of ESAs were randomized 1:1 to treatment either with subcutaneous luspatercept (starting dose, 1.0 mg/kg with titration up to 1.75 mg/kg; n = 178) once every 3 weeks or subcutaneous epoetin alfa (starting dose, 450 IU/kg with titration up to 1,050 IU/kg; n = 176) once every week, for a minimum of 24 weeks.

Patients in each arm were also able to receive best supportive care, including blood transfusions. Their baseline characteristics were similar in each arm.

For the primary endpoint, patients receiving luspatercept in the intent-to-treat population were nearly twice as likely as those treated with epoetin alfa to become independent of RBC transfusions, with a concurrent mean hemoglobin increase of 1.5 g/dL or more, for at least 12 weeks in the first 24 weeks on study, at a rate of 58.5% with luspatercept versus 31.2% with epoetin alfa (P < .0001).

In addition, patients treated with luspatercept had a longer median duration of transfusion independence, at 126.6 weeks versus 77 weeks in the epoetin alfa group (hazard ratio, 0.456).

Importantly, the statistically significant improvement with luspatercept was consistent among patients with ring sideroblasts (HR, 0.626) as well as without them (HR, 0.492). Dr. Garcia-Manero noted that about 70% of patients in the study had ring sideroblasts, consistent with their common occurrence in LR-MDS.

Luspatercept was also superior in secondary endpoints, including in achieving hematologic improvement, with an erythroid response of at least 8 weeks, per International Working Group 2006 criteria, which was achieved by 74.1% with luspatercept versus 51.3% with epoetin alfa (P < .0001).

The greater improvement with luspatercept was also observed in other subgroups, including based on baseline serum erythropoietin or levels of transfusion dependence, as well as SF381 mutation status.

In terms of safety, treatment emergent adverse events (TEAEs) of any grade were reported among 92.1% of luspatercept and 85.2% of epoetin alfa patients. Longer-term posttreatment safety analyses showed no significant differences between the groups in terms of progression to high-risk MDS, in five (2.8%) with luspatercept and seven(4.0%) epoetin alfa, and progression to acute myeloid leukemia, occurring in four (2.2%) luspatercept and five (2.8%) epoetin alfa patients.

Overall rates of death between the groups were also similar during the treatment and posttreatment periods (32 [18.0%] luspatercept; 32 [18.2%] epoetin alfa patients).

“The toxicity profile was consistent with previous clinical experience,” Dr. Garcia-Manero said.

Dr. Garcia-Manero underscored that “the results of the COMMANDS trial are very important.”

“ESAs are really not optimal agents [for LR-MDS], and these results indicate that luspatercept almost doubles response rates in this patient population, therefore becoming potentially the standard of care for patients with transfusion-dependent LR-MDS who have not received prior ESA treatment,” he said.

Further commenting, Dr. Artz added that the effects in patient subgroups will be of great interest as further data on luspatercept emerges.

“Of highest interest will be the differential responses among patients with and without ring sideroblasts, as well as by SF3B1 mutational status,” he said. Furthermore, “patient-centric data emerge as even more relevant when considering the quantitatively higher rates of treatment-emergent adverse effects in the luspatercept arm.”

“We need to understand how to best sequence anemia therapies in low-risk MDS when we have two active agents, or even if [there is] a role for combined ESA/luspatercept therapy,” he noted.

“The results are exciting, but we need the final data including relevant subsets before declaring luspatercept the winner,” Dr. Artz concluded.

The study was sponsored by Celgene/Bristol-Myers Squibb. Dr. Garcia-Manero reported relationships with Abbvie, Acceleron Pharma, Aprea Therapeutics, Astex Pharmaceuticals, Bristol-Myers Squibb, Genentech, Gilead Sciences, and Novartis. Dr. Artz disclosed previous consulting relationships with Abbvie and Magenta Therapeutics.

The first-in-class erythroid maturation agent luspatercept showed significant improvement over the erythropoiesis-stimulating agent epoetin alfa in reducing dependency on red blood cell transfusions among patients with lower-risk myelodysplastic syndromes (LR-MDS) who are ESA naive.

“Luspatercept is the first and only therapy to demonstrate superiority in a head-to-head study against ESAs in [transfusion-dependent] LR-MDS,” first author Guillermo Garcia-Manero, MD, chief of the MDS section, department of leukemia, at the University of Texas MD Anderson Cancer Center, Houston, said in a premeeting press briefing in advance of the annual meeting of the American Society of Clinical Oncology.

“It should be considered a paradigm shift in the treatment of LR-MDS–associated anemia,” Dr. Garcia-Manero said.

Commenting on the study, Andrew Artz, MD, a professor at the Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, Calif., agreed that the results could be practice changing.

“We biologically expected luspatercept to best ESA [in ring sideroblast transfusion–dependent MDS], based on luspatercept often rescuing ESA failures in this setting,” Dr. Artz said in an interview.

“The results have the potential to change initial therapy for patients with low-risk red blood cell transfusion-dependent MDS,” he said.

In LR-MDS, which encompasses a variety of bone marrow disorders, chronic anemia is very common, and patients, who are typically elderly, can become burdened by developing dependencies on RBC transfusions.

Transfusion dependency, in addition to creating a host of challenges, can increase the risk of death by as much as 50%, compared with patients who are not transfusion dependent, Dr. Garcia-Manero noted.

While ESAs such as epoetin alfa are the first-line treatment for LR-MDS, patients who are dependent on transfusions are less likely to respond to the agents, hence “there is an unmet need for effective and durable options other than ESAs for treating anemia in patients with LR-MDS,” Dr. Garcia-Manero said.

Luspatercept, a first-in-class monoclonal antibody, has a mechanism of action that is distinct from ESAs, modulating the transforming growth factor–beta pathway and increasing erythrocytosis.

In the previous phase 3 MEDALIST trial, the drug was shown to have efficacy over placebo in reducing the severity of anemia in LR-MDS. In 2020, in what was deemed the first advance in MDS treatment in more than a decade, those results led to approval by the Food and Drug Administration for patients with LR-MDS with ring sideroblasts who are transfusion dependent and are refractory, intolerant, or ineligible to receive ESAs.

To further investigate luspatercept’s efficacy in a head-to-head comparison with an ESA in LR-MDS patients who are ESA naive, Dr. Garcia-Manero and colleagues conducted the phase 3 COMMANDS trial.

For the global, open-label study, patients with LR-MDS who were dependent on RBC transfusions and had no prior use of ESAs were randomized 1:1 to treatment either with subcutaneous luspatercept (starting dose, 1.0 mg/kg with titration up to 1.75 mg/kg; n = 178) once every 3 weeks or subcutaneous epoetin alfa (starting dose, 450 IU/kg with titration up to 1,050 IU/kg; n = 176) once every week, for a minimum of 24 weeks.

Patients in each arm were also able to receive best supportive care, including blood transfusions. Their baseline characteristics were similar in each arm.

For the primary endpoint, patients receiving luspatercept in the intent-to-treat population were nearly twice as likely as those treated with epoetin alfa to become independent of RBC transfusions, with a concurrent mean hemoglobin increase of 1.5 g/dL or more, for at least 12 weeks in the first 24 weeks on study, at a rate of 58.5% with luspatercept versus 31.2% with epoetin alfa (P < .0001).

In addition, patients treated with luspatercept had a longer median duration of transfusion independence, at 126.6 weeks versus 77 weeks in the epoetin alfa group (hazard ratio, 0.456).

Importantly, the statistically significant improvement with luspatercept was consistent among patients with ring sideroblasts (HR, 0.626) as well as without them (HR, 0.492). Dr. Garcia-Manero noted that about 70% of patients in the study had ring sideroblasts, consistent with their common occurrence in LR-MDS.

Luspatercept was also superior in secondary endpoints, including in achieving hematologic improvement, with an erythroid response of at least 8 weeks, per International Working Group 2006 criteria, which was achieved by 74.1% with luspatercept versus 51.3% with epoetin alfa (P < .0001).

The greater improvement with luspatercept was also observed in other subgroups, including based on baseline serum erythropoietin or levels of transfusion dependence, as well as SF381 mutation status.

In terms of safety, treatment emergent adverse events (TEAEs) of any grade were reported among 92.1% of luspatercept and 85.2% of epoetin alfa patients. Longer-term posttreatment safety analyses showed no significant differences between the groups in terms of progression to high-risk MDS, in five (2.8%) with luspatercept and seven(4.0%) epoetin alfa, and progression to acute myeloid leukemia, occurring in four (2.2%) luspatercept and five (2.8%) epoetin alfa patients.

Overall rates of death between the groups were also similar during the treatment and posttreatment periods (32 [18.0%] luspatercept; 32 [18.2%] epoetin alfa patients).

“The toxicity profile was consistent with previous clinical experience,” Dr. Garcia-Manero said.

Dr. Garcia-Manero underscored that “the results of the COMMANDS trial are very important.”

“ESAs are really not optimal agents [for LR-MDS], and these results indicate that luspatercept almost doubles response rates in this patient population, therefore becoming potentially the standard of care for patients with transfusion-dependent LR-MDS who have not received prior ESA treatment,” he said.

Further commenting, Dr. Artz added that the effects in patient subgroups will be of great interest as further data on luspatercept emerges.

“Of highest interest will be the differential responses among patients with and without ring sideroblasts, as well as by SF3B1 mutational status,” he said. Furthermore, “patient-centric data emerge as even more relevant when considering the quantitatively higher rates of treatment-emergent adverse effects in the luspatercept arm.”

“We need to understand how to best sequence anemia therapies in low-risk MDS when we have two active agents, or even if [there is] a role for combined ESA/luspatercept therapy,” he noted.

“The results are exciting, but we need the final data including relevant subsets before declaring luspatercept the winner,” Dr. Artz concluded.

The study was sponsored by Celgene/Bristol-Myers Squibb. Dr. Garcia-Manero reported relationships with Abbvie, Acceleron Pharma, Aprea Therapeutics, Astex Pharmaceuticals, Bristol-Myers Squibb, Genentech, Gilead Sciences, and Novartis. Dr. Artz disclosed previous consulting relationships with Abbvie and Magenta Therapeutics.

The first-in-class erythroid maturation agent luspatercept showed significant improvement over the erythropoiesis-stimulating agent epoetin alfa in reducing dependency on red blood cell transfusions among patients with lower-risk myelodysplastic syndromes (LR-MDS) who are ESA naive.

“Luspatercept is the first and only therapy to demonstrate superiority in a head-to-head study against ESAs in [transfusion-dependent] LR-MDS,” first author Guillermo Garcia-Manero, MD, chief of the MDS section, department of leukemia, at the University of Texas MD Anderson Cancer Center, Houston, said in a premeeting press briefing in advance of the annual meeting of the American Society of Clinical Oncology.

“It should be considered a paradigm shift in the treatment of LR-MDS–associated anemia,” Dr. Garcia-Manero said.

Commenting on the study, Andrew Artz, MD, a professor at the Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, Calif., agreed that the results could be practice changing.

“We biologically expected luspatercept to best ESA [in ring sideroblast transfusion–dependent MDS], based on luspatercept often rescuing ESA failures in this setting,” Dr. Artz said in an interview.

“The results have the potential to change initial therapy for patients with low-risk red blood cell transfusion-dependent MDS,” he said.

In LR-MDS, which encompasses a variety of bone marrow disorders, chronic anemia is very common, and patients, who are typically elderly, can become burdened by developing dependencies on RBC transfusions.

Transfusion dependency, in addition to creating a host of challenges, can increase the risk of death by as much as 50%, compared with patients who are not transfusion dependent, Dr. Garcia-Manero noted.

While ESAs such as epoetin alfa are the first-line treatment for LR-MDS, patients who are dependent on transfusions are less likely to respond to the agents, hence “there is an unmet need for effective and durable options other than ESAs for treating anemia in patients with LR-MDS,” Dr. Garcia-Manero said.

Luspatercept, a first-in-class monoclonal antibody, has a mechanism of action that is distinct from ESAs, modulating the transforming growth factor–beta pathway and increasing erythrocytosis.

In the previous phase 3 MEDALIST trial, the drug was shown to have efficacy over placebo in reducing the severity of anemia in LR-MDS. In 2020, in what was deemed the first advance in MDS treatment in more than a decade, those results led to approval by the Food and Drug Administration for patients with LR-MDS with ring sideroblasts who are transfusion dependent and are refractory, intolerant, or ineligible to receive ESAs.

To further investigate luspatercept’s efficacy in a head-to-head comparison with an ESA in LR-MDS patients who are ESA naive, Dr. Garcia-Manero and colleagues conducted the phase 3 COMMANDS trial.

For the global, open-label study, patients with LR-MDS who were dependent on RBC transfusions and had no prior use of ESAs were randomized 1:1 to treatment either with subcutaneous luspatercept (starting dose, 1.0 mg/kg with titration up to 1.75 mg/kg; n = 178) once every 3 weeks or subcutaneous epoetin alfa (starting dose, 450 IU/kg with titration up to 1,050 IU/kg; n = 176) once every week, for a minimum of 24 weeks.

Patients in each arm were also able to receive best supportive care, including blood transfusions. Their baseline characteristics were similar in each arm.

For the primary endpoint, patients receiving luspatercept in the intent-to-treat population were nearly twice as likely as those treated with epoetin alfa to become independent of RBC transfusions, with a concurrent mean hemoglobin increase of 1.5 g/dL or more, for at least 12 weeks in the first 24 weeks on study, at a rate of 58.5% with luspatercept versus 31.2% with epoetin alfa (P < .0001).

In addition, patients treated with luspatercept had a longer median duration of transfusion independence, at 126.6 weeks versus 77 weeks in the epoetin alfa group (hazard ratio, 0.456).

Importantly, the statistically significant improvement with luspatercept was consistent among patients with ring sideroblasts (HR, 0.626) as well as without them (HR, 0.492). Dr. Garcia-Manero noted that about 70% of patients in the study had ring sideroblasts, consistent with their common occurrence in LR-MDS.

Luspatercept was also superior in secondary endpoints, including in achieving hematologic improvement, with an erythroid response of at least 8 weeks, per International Working Group 2006 criteria, which was achieved by 74.1% with luspatercept versus 51.3% with epoetin alfa (P < .0001).

The greater improvement with luspatercept was also observed in other subgroups, including based on baseline serum erythropoietin or levels of transfusion dependence, as well as SF381 mutation status.

In terms of safety, treatment emergent adverse events (TEAEs) of any grade were reported among 92.1% of luspatercept and 85.2% of epoetin alfa patients. Longer-term posttreatment safety analyses showed no significant differences between the groups in terms of progression to high-risk MDS, in five (2.8%) with luspatercept and seven(4.0%) epoetin alfa, and progression to acute myeloid leukemia, occurring in four (2.2%) luspatercept and five (2.8%) epoetin alfa patients.

Overall rates of death between the groups were also similar during the treatment and posttreatment periods (32 [18.0%] luspatercept; 32 [18.2%] epoetin alfa patients).

“The toxicity profile was consistent with previous clinical experience,” Dr. Garcia-Manero said.

Dr. Garcia-Manero underscored that “the results of the COMMANDS trial are very important.”

“ESAs are really not optimal agents [for LR-MDS], and these results indicate that luspatercept almost doubles response rates in this patient population, therefore becoming potentially the standard of care for patients with transfusion-dependent LR-MDS who have not received prior ESA treatment,” he said.

Further commenting, Dr. Artz added that the effects in patient subgroups will be of great interest as further data on luspatercept emerges.

“Of highest interest will be the differential responses among patients with and without ring sideroblasts, as well as by SF3B1 mutational status,” he said. Furthermore, “patient-centric data emerge as even more relevant when considering the quantitatively higher rates of treatment-emergent adverse effects in the luspatercept arm.”

“We need to understand how to best sequence anemia therapies in low-risk MDS when we have two active agents, or even if [there is] a role for combined ESA/luspatercept therapy,” he noted.

“The results are exciting, but we need the final data including relevant subsets before declaring luspatercept the winner,” Dr. Artz concluded.

The study was sponsored by Celgene/Bristol-Myers Squibb. Dr. Garcia-Manero reported relationships with Abbvie, Acceleron Pharma, Aprea Therapeutics, Astex Pharmaceuticals, Bristol-Myers Squibb, Genentech, Gilead Sciences, and Novartis. Dr. Artz disclosed previous consulting relationships with Abbvie and Magenta Therapeutics.

Detection of circulating tumor DNA was significantly associated with worse rates of disease-free and overall survival in patients with stage I-III breast cancer, a new meta-analysis and systematic review found.

“Circulating tumor DNA (ctDNA) has been extensively studied as a prognostic biomarker in early breast cancer. However, there is a significant heterogeneity in the study results, which is probably related to the fact that each individual study included different patient populations, collected blood at different time points, and used different methods (assays) for ctDNA analysis,” said Guilherme Nader Marta, MD, of the Institut Jules Bordet, Anderlecht, Belgium, in an interview.

“The aim of our study was to summarize the available evidence that has been presented so far on this topic by performing a systematic review and meta-analysis including studies that reported the association between ctDNA detection and long-term outcomes,” said Dr. Nader Marta, who coauthored the new research, which was presented as a poster (Poster 26P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
 

Methods and results

The authors identified 57 studies including data from 5,729 individuals with early breast cancer. The 44.5% for whom stages were reported consisted of 18.3% with stage I disease, 60.0% with stage II, and 21.5% with stage III. Patients’ ctDNA collection was divided into three groups: baseline, after neoadjuvant therapy (End-of-NAT), and during follow-up care; ctDNA assays were classified as tumor-informed or non–tumor-informed.

The detection of ctDNA at any time point during diagnosis and treatment was associated with worse disease-free survival (DFS) and overall survival (OS), compared with no ctDNA. The association was stronger in tumor-informed assays, the researchers said.

For disease-free survival, the overall multivariate hazard ratios were 2.5, 5.5, and 7.2 for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.

For overall survival, the overall multivariate hazard ratios were 3.0, 12.9, and 5.6, for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.

The pooled hazard ratios were numerically higher for both DFS and OS when ctDNA was detected at either End-of-NAT or follow-up.

In addition, detection of ctDNA was associated with a high degree of specificity (from 0.7 to 1.0) for breast cancer relapse; sensitivity ranged from 0.31 to 1.0, the researchers noted. The mean lead time from ctDNA detection to breast cancer recurrence in these cases was approximately 10 months.
 

Results show ctDNA detection is associated with worse survival

“Our study results demonstrate that ctDNA detection is associated with worse disease-free survival and overall survival in patients with early breast cancer, particularly when measured after treatment with tumor-informed assays,” Dr. Nader Marta said in an interview.

“As next steps, we need to build on this evidence to bring the potential benefits of this powerful prognostic tool to our patients,” said Dr. Nader Marta. “Ongoing studies exploring different management strategies based on serial ctDNA assessments will help us understand the exact role of this technology in our clinical practice.”

The study received no outside funding. Dr. Nader Marta disclosed relationships with companies including Roche and Bayer.
 

Detection of circulating tumor DNA was significantly associated with worse rates of disease-free and overall survival in patients with stage I-III breast cancer, a new meta-analysis and systematic review found.

“Circulating tumor DNA (ctDNA) has been extensively studied as a prognostic biomarker in early breast cancer. However, there is a significant heterogeneity in the study results, which is probably related to the fact that each individual study included different patient populations, collected blood at different time points, and used different methods (assays) for ctDNA analysis,” said Guilherme Nader Marta, MD, of the Institut Jules Bordet, Anderlecht, Belgium, in an interview.

“The aim of our study was to summarize the available evidence that has been presented so far on this topic by performing a systematic review and meta-analysis including studies that reported the association between ctDNA detection and long-term outcomes,” said Dr. Nader Marta, who coauthored the new research, which was presented as a poster (Poster 26P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
 

Methods and results

The authors identified 57 studies including data from 5,729 individuals with early breast cancer. The 44.5% for whom stages were reported consisted of 18.3% with stage I disease, 60.0% with stage II, and 21.5% with stage III. Patients’ ctDNA collection was divided into three groups: baseline, after neoadjuvant therapy (End-of-NAT), and during follow-up care; ctDNA assays were classified as tumor-informed or non–tumor-informed.

The detection of ctDNA at any time point during diagnosis and treatment was associated with worse disease-free survival (DFS) and overall survival (OS), compared with no ctDNA. The association was stronger in tumor-informed assays, the researchers said.

For disease-free survival, the overall multivariate hazard ratios were 2.5, 5.5, and 7.2 for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.

For overall survival, the overall multivariate hazard ratios were 3.0, 12.9, and 5.6, for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.

The pooled hazard ratios were numerically higher for both DFS and OS when ctDNA was detected at either End-of-NAT or follow-up.

In addition, detection of ctDNA was associated with a high degree of specificity (from 0.7 to 1.0) for breast cancer relapse; sensitivity ranged from 0.31 to 1.0, the researchers noted. The mean lead time from ctDNA detection to breast cancer recurrence in these cases was approximately 10 months.
 

Results show ctDNA detection is associated with worse survival

“Our study results demonstrate that ctDNA detection is associated with worse disease-free survival and overall survival in patients with early breast cancer, particularly when measured after treatment with tumor-informed assays,” Dr. Nader Marta said in an interview.

“As next steps, we need to build on this evidence to bring the potential benefits of this powerful prognostic tool to our patients,” said Dr. Nader Marta. “Ongoing studies exploring different management strategies based on serial ctDNA assessments will help us understand the exact role of this technology in our clinical practice.”

The study received no outside funding. Dr. Nader Marta disclosed relationships with companies including Roche and Bayer.
 

Detection of circulating tumor DNA was significantly associated with worse rates of disease-free and overall survival in patients with stage I-III breast cancer, a new meta-analysis and systematic review found.

“Circulating tumor DNA (ctDNA) has been extensively studied as a prognostic biomarker in early breast cancer. However, there is a significant heterogeneity in the study results, which is probably related to the fact that each individual study included different patient populations, collected blood at different time points, and used different methods (assays) for ctDNA analysis,” said Guilherme Nader Marta, MD, of the Institut Jules Bordet, Anderlecht, Belgium, in an interview.

“The aim of our study was to summarize the available evidence that has been presented so far on this topic by performing a systematic review and meta-analysis including studies that reported the association between ctDNA detection and long-term outcomes,” said Dr. Nader Marta, who coauthored the new research, which was presented as a poster (Poster 26P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.
 

Methods and results

The authors identified 57 studies including data from 5,729 individuals with early breast cancer. The 44.5% for whom stages were reported consisted of 18.3% with stage I disease, 60.0% with stage II, and 21.5% with stage III. Patients’ ctDNA collection was divided into three groups: baseline, after neoadjuvant therapy (End-of-NAT), and during follow-up care; ctDNA assays were classified as tumor-informed or non–tumor-informed.

The detection of ctDNA at any time point during diagnosis and treatment was associated with worse disease-free survival (DFS) and overall survival (OS), compared with no ctDNA. The association was stronger in tumor-informed assays, the researchers said.

For disease-free survival, the overall multivariate hazard ratios were 2.5, 5.5, and 7.2 for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.

For overall survival, the overall multivariate hazard ratios were 3.0, 12.9, and 5.6, for ctDNA detection at baseline, End-of-NAT, and follow-up, respectively.

The pooled hazard ratios were numerically higher for both DFS and OS when ctDNA was detected at either End-of-NAT or follow-up.

In addition, detection of ctDNA was associated with a high degree of specificity (from 0.7 to 1.0) for breast cancer relapse; sensitivity ranged from 0.31 to 1.0, the researchers noted. The mean lead time from ctDNA detection to breast cancer recurrence in these cases was approximately 10 months.
 

Results show ctDNA detection is associated with worse survival

“Our study results demonstrate that ctDNA detection is associated with worse disease-free survival and overall survival in patients with early breast cancer, particularly when measured after treatment with tumor-informed assays,” Dr. Nader Marta said in an interview.

“As next steps, we need to build on this evidence to bring the potential benefits of this powerful prognostic tool to our patients,” said Dr. Nader Marta. “Ongoing studies exploring different management strategies based on serial ctDNA assessments will help us understand the exact role of this technology in our clinical practice.”

The study received no outside funding. Dr. Nader Marta disclosed relationships with companies including Roche and Bayer.
 

A new study finds that racial disparities in male breast cancer are persisting in the United States.

From 2000 to 2019, Black men were diagnosed at later ages than White males (median ages, 69 and 63 years, respectively) and were more likely to die from the disease (22.4% vs. 16.8%, respectively). Male breast cancer (MBC) was more likely to kill Black men in rural vs. urban areas (hazard ratio = 1.4; 95% confidence interval, 1.0-2.1; P less than .05). Among White males, in contrast, there was no difference on that front, according to the research, which was presented in a poster (Abstract No. 87P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

It’s not clear why the disparities exist, said lead author Lekha Yadukumar, MBBS, an internal medicine resident at the Wright Center for Graduate Medical Education in Scranton, Penn., in an interview.

“Several potential factors may contribute to the higher rate of breast cancer diagnosis in older [Black] men, including the pathology of the disease, limited awareness about breast cancer, and potential barriers to accessibility,” she said. “The increased mortality among [Black men] may be linked to variations in tumor pathology and molecular biology. Social factors may also potentially impact survival rates, including [having] limited access to health care in rural areas and inadequate social support.”

Male breast cancer is rare, accounting for less than 1% of all breast cancer cases in the United States, according to the Breast Cancer Research Foundation. An estimated 2,700 men are diagnosed each year, and about 530 will die. Previous research has suggested Black men have worse outcomes than White men, but the data covered earlier years than the new study.
 

Methods and results

Dr. Yadukumar and colleagues retrospectively analyzed statistics from the Surveillance, Epidemiology, and End Results database for patients diagnosed with primary male breast cancer from 2000 to 2019 (n = 8,373; Black men, 1,111 [13.26%]; White men, 6,817 [81.41%]).

Median income didn’t affect mortality, whereas men in both racial groups were less likely to die if they were married vs. single/divorced (hazard ratio = 0.6; P less than .05).

Other studies have shown that “[Black American] men diagnosed with breast cancer experience longer time intervals before receiving treatment, encounter more severe disease manifestations, and exhibit lower rates of survivorship,” Dr. Yadukumar said. “Despite these findings, there remains a scarcity of genetic studies aimed at comprehending the underlying causes of these disparities. Moreover, there is a dearth of research investigating other factors that may influence survival outcomes among men with breast cancer.”
 

Findings reflect the disparities in female breast cancer

In an interview, Duke University, Durham, N.C., oncologist Arif Kamal, MD, MBA, MHS, the chief patient officer at the American Cancer Society, said the study is impressive since the number of patients is large for a rare cancer and the population is diverse. Plus, the findings reflect the disparities in female breast cancer, he noted.

“We know that Black women’s mortality is worse vs. White women in breast cancer, and we believe that most of that has nothing to do with cancer screening,” said Dr. Kamal, who was not involved in the new study. “When the clock starts from diagnosis onwards, you start to see less introduction to clinical trials and standard care medications and more time to treatment, surgery, and radiation,” he said.

“You see similar disparities as related to mortality in Black vs. White men,” he noted.

The new findings about higher death rates for Black men, especially in rural areas, suggest that “distance matters, and race matters,” he said. In rural areas, it can be hard to access pathologists, radiologists, and surgeons with more experience with breast cancer, he said.

But, he noted, the study finds that income doesn’t appear to be a factor.

In the big picture, he said, the results suggest that when it comes to barriers to better outcomes, “things that are systemic don’t make exceptions because you are a man vs. a woman.”

No study funding was reported. The study authors and Dr. Kamal have no relevant financial disclosures.
 

A new study finds that racial disparities in male breast cancer are persisting in the United States.

From 2000 to 2019, Black men were diagnosed at later ages than White males (median ages, 69 and 63 years, respectively) and were more likely to die from the disease (22.4% vs. 16.8%, respectively). Male breast cancer (MBC) was more likely to kill Black men in rural vs. urban areas (hazard ratio = 1.4; 95% confidence interval, 1.0-2.1; P less than .05). Among White males, in contrast, there was no difference on that front, according to the research, which was presented in a poster (Abstract No. 87P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

It’s not clear why the disparities exist, said lead author Lekha Yadukumar, MBBS, an internal medicine resident at the Wright Center for Graduate Medical Education in Scranton, Penn., in an interview.

“Several potential factors may contribute to the higher rate of breast cancer diagnosis in older [Black] men, including the pathology of the disease, limited awareness about breast cancer, and potential barriers to accessibility,” she said. “The increased mortality among [Black men] may be linked to variations in tumor pathology and molecular biology. Social factors may also potentially impact survival rates, including [having] limited access to health care in rural areas and inadequate social support.”

Male breast cancer is rare, accounting for less than 1% of all breast cancer cases in the United States, according to the Breast Cancer Research Foundation. An estimated 2,700 men are diagnosed each year, and about 530 will die. Previous research has suggested Black men have worse outcomes than White men, but the data covered earlier years than the new study.
 

Methods and results

Dr. Yadukumar and colleagues retrospectively analyzed statistics from the Surveillance, Epidemiology, and End Results database for patients diagnosed with primary male breast cancer from 2000 to 2019 (n = 8,373; Black men, 1,111 [13.26%]; White men, 6,817 [81.41%]).

Median income didn’t affect mortality, whereas men in both racial groups were less likely to die if they were married vs. single/divorced (hazard ratio = 0.6; P less than .05).

Other studies have shown that “[Black American] men diagnosed with breast cancer experience longer time intervals before receiving treatment, encounter more severe disease manifestations, and exhibit lower rates of survivorship,” Dr. Yadukumar said. “Despite these findings, there remains a scarcity of genetic studies aimed at comprehending the underlying causes of these disparities. Moreover, there is a dearth of research investigating other factors that may influence survival outcomes among men with breast cancer.”
 

Findings reflect the disparities in female breast cancer

In an interview, Duke University, Durham, N.C., oncologist Arif Kamal, MD, MBA, MHS, the chief patient officer at the American Cancer Society, said the study is impressive since the number of patients is large for a rare cancer and the population is diverse. Plus, the findings reflect the disparities in female breast cancer, he noted.

“We know that Black women’s mortality is worse vs. White women in breast cancer, and we believe that most of that has nothing to do with cancer screening,” said Dr. Kamal, who was not involved in the new study. “When the clock starts from diagnosis onwards, you start to see less introduction to clinical trials and standard care medications and more time to treatment, surgery, and radiation,” he said.

“You see similar disparities as related to mortality in Black vs. White men,” he noted.

The new findings about higher death rates for Black men, especially in rural areas, suggest that “distance matters, and race matters,” he said. In rural areas, it can be hard to access pathologists, radiologists, and surgeons with more experience with breast cancer, he said.

But, he noted, the study finds that income doesn’t appear to be a factor.

In the big picture, he said, the results suggest that when it comes to barriers to better outcomes, “things that are systemic don’t make exceptions because you are a man vs. a woman.”

No study funding was reported. The study authors and Dr. Kamal have no relevant financial disclosures.
 

A new study finds that racial disparities in male breast cancer are persisting in the United States.

From 2000 to 2019, Black men were diagnosed at later ages than White males (median ages, 69 and 63 years, respectively) and were more likely to die from the disease (22.4% vs. 16.8%, respectively). Male breast cancer (MBC) was more likely to kill Black men in rural vs. urban areas (hazard ratio = 1.4; 95% confidence interval, 1.0-2.1; P less than .05). Among White males, in contrast, there was no difference on that front, according to the research, which was presented in a poster (Abstract No. 87P) at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

It’s not clear why the disparities exist, said lead author Lekha Yadukumar, MBBS, an internal medicine resident at the Wright Center for Graduate Medical Education in Scranton, Penn., in an interview.

“Several potential factors may contribute to the higher rate of breast cancer diagnosis in older [Black] men, including the pathology of the disease, limited awareness about breast cancer, and potential barriers to accessibility,” she said. “The increased mortality among [Black men] may be linked to variations in tumor pathology and molecular biology. Social factors may also potentially impact survival rates, including [having] limited access to health care in rural areas and inadequate social support.”

Male breast cancer is rare, accounting for less than 1% of all breast cancer cases in the United States, according to the Breast Cancer Research Foundation. An estimated 2,700 men are diagnosed each year, and about 530 will die. Previous research has suggested Black men have worse outcomes than White men, but the data covered earlier years than the new study.
 

Methods and results

Dr. Yadukumar and colleagues retrospectively analyzed statistics from the Surveillance, Epidemiology, and End Results database for patients diagnosed with primary male breast cancer from 2000 to 2019 (n = 8,373; Black men, 1,111 [13.26%]; White men, 6,817 [81.41%]).

Median income didn’t affect mortality, whereas men in both racial groups were less likely to die if they were married vs. single/divorced (hazard ratio = 0.6; P less than .05).

Other studies have shown that “[Black American] men diagnosed with breast cancer experience longer time intervals before receiving treatment, encounter more severe disease manifestations, and exhibit lower rates of survivorship,” Dr. Yadukumar said. “Despite these findings, there remains a scarcity of genetic studies aimed at comprehending the underlying causes of these disparities. Moreover, there is a dearth of research investigating other factors that may influence survival outcomes among men with breast cancer.”
 

Findings reflect the disparities in female breast cancer

In an interview, Duke University, Durham, N.C., oncologist Arif Kamal, MD, MBA, MHS, the chief patient officer at the American Cancer Society, said the study is impressive since the number of patients is large for a rare cancer and the population is diverse. Plus, the findings reflect the disparities in female breast cancer, he noted.

“We know that Black women’s mortality is worse vs. White women in breast cancer, and we believe that most of that has nothing to do with cancer screening,” said Dr. Kamal, who was not involved in the new study. “When the clock starts from diagnosis onwards, you start to see less introduction to clinical trials and standard care medications and more time to treatment, surgery, and radiation,” he said.

“You see similar disparities as related to mortality in Black vs. White men,” he noted.

The new findings about higher death rates for Black men, especially in rural areas, suggest that “distance matters, and race matters,” he said. In rural areas, it can be hard to access pathologists, radiologists, and surgeons with more experience with breast cancer, he said.

But, he noted, the study finds that income doesn’t appear to be a factor.

In the big picture, he said, the results suggest that when it comes to barriers to better outcomes, “things that are systemic don’t make exceptions because you are a man vs. a woman.”

No study funding was reported. The study authors and Dr. Kamal have no relevant financial disclosures.
 

CHICAGO - The American Urological Association and the Society of Urologic Oncology (SUO) for the first time have taken a position on the type of biopsy men with prostate lesions should undergo, endorsing both transperineal and transrectal biopsy instead of choosing one over the other.

The new guidelines, issued at the annual meeting of the American Urological Association, contrast with 2021 recommendations from the European Association of Urologists (EAU), which regard the transperineal approach as superior to and safer than the transrectal approach.

The new guidelines state: “Clinicians may use either a transrectal or transperineal biopsy route when performing a biopsy. (Conditional Recommendation; Evidence Level: Grade C).” Grade C is the lowest grade of acceptance the guideline committee could issue, according to Daniel Lin, MD, vice-chair of the AUA guideline panel.

“The AUA looked at all the higher-level data comparing the two procedures. There was a lack of that data,” Dr. Lin, chief of urologic oncology at the University of Washington, Seattle, said in an interview. He said the literature consists mainly of systematic single-center reviews, rather than multicenter randomized trials.

But Hendrik Van Poppel, MD, policy chief for the EAU, said that in Europe, transrectal biopsies are now considered “medical malpractice.”

Philip Cornford, MD, associate professor of urology at the University of Liverpool, England, and chair of the prostate biopsy guidelines panel for the EAU, said the society in 2021 concluded that the transperineal approach is the preferred one.

The EAU stated that transperineal prostate biopsies should be performed “due to the lower risk of infectious complications.” The EAU described the evidence as strong: A meta-analysis of seven studies that included 1,330 patients showed that for patients undergoing transperineal biopsy, infectious complications were significantly reduced.

Dr. Cornford said in essence, the EAU made its decision out of concern about infections, whereas the AUA and SUO based their decision on the ability of the methods to detect cancer.

Advocates for transperineal procedures cite several studies that show that the rate of infection, including sepsis, with such biopsies is virtually zero.

However, Dr. Lin noted that the committee said existing data on infection did not support this position. He also cited a “a fairly compelling” single-center randomized study with 750 patients that showed no difference in infection rates. The study was presented at the AUA meeting.
 

Agents of death and destruction?

Badar Mian, MD, professor of surgery at Albany (N.Y.) Medical College, who led the study, told an AUA session that urology has been trapped in an “echo chamber” regarding the relative safety of biopsies.

Clinicians hear “loud proclamations, which get repeated and magnified, that there is a real zero risk of complications after transperineal biopsies as compared to the horrendous 5% to 10% or higher rate of transrectal biopsy complications and that you, with your transrectal biopsies, are the cause of death and destruction all around,” Dr. Mian said. “Well, if you step out of the echo chamber, what you’ll find is that the accurate complications amongst the two procedures are not that dramatically different, much less dramatic than what you’ve been told to believe.”

The campaign to end transrectal biopsies in Europe started in 2018 with the death of a Norwegian man who experienced an infection after the procedure. Truls Bjerklund Johansen, MD, who’d performed the biopsy on the patient and who worked with the man’s daughter to change national practice, persuaded the EAU to look at the issue.

Advocates also say transperineal biopsies are better at detecting anterior and apical cancers.

“I would agree the data on cancer detection is less convincing, but that is not the basis of the EAU recommendation,” Dr. Cornford said.

Arvin George, MD, leads the transperineal biopsy program at the University of Michigan, Ann Arbor, and directs the transperineal training program at the AUA’s annual meeting. He said his course was sold out early and included about 60 trainees.

Dr. George said the new guideline statement “is not an unequivocal endorsement for transperineal biopsy as the preferred approach for diagnostic sampling but rather an acknowledgment of this approach as an alternative option.”

He said that although the new position statement should increase awareness of the transperineal approach in the United States, “without a strong recommendation, the guideline statement is unlikely to spark a large switch to the transperineal biopsy but rather supports the continued slow and steady adoption.”

Matthew Allaway, DO, founder of Perineologic, developer of the PrecisionPoint Transperineal Access System, said industry figures show that about 10% of the 1.5 million prostate biopsies performed in the United States annually are performed transperineally, a doubling in 2 years.

Jeremy Grummet, MD, clinical professor of urology at Monash University, Melbourne, and leader of the TREXIT (Transperineal Exit) movement to abandon transrectal procedures, said the AUA guidelines are biased toward “physician convenience.”
 

Lack of training

The AUA said another reason it did not endorse the transperineal approach was that currently, American urologists lack training and experience with transperineal procedures.

Dr. Grummet blamed major medical centers for any gap in the familiarity of clinicians with transperineal biopsies, which have been available for more than a decade.

“It is incumbent on the leaders of urology departments globally to ensure that their colleagues are trained in transperineal biopsy and have access to the appropriate equipment,” he said in an interview. “Lack of training didn’t seem to prevent the rapid uptake of robotic prostatectomy – a far more complex procedure.”

The authors have disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

CHICAGO - The American Urological Association and the Society of Urologic Oncology (SUO) for the first time have taken a position on the type of biopsy men with prostate lesions should undergo, endorsing both transperineal and transrectal biopsy instead of choosing one over the other.

The new guidelines, issued at the annual meeting of the American Urological Association, contrast with 2021 recommendations from the European Association of Urologists (EAU), which regard the transperineal approach as superior to and safer than the transrectal approach.

The new guidelines state: “Clinicians may use either a transrectal or transperineal biopsy route when performing a biopsy. (Conditional Recommendation; Evidence Level: Grade C).” Grade C is the lowest grade of acceptance the guideline committee could issue, according to Daniel Lin, MD, vice-chair of the AUA guideline panel.

“The AUA looked at all the higher-level data comparing the two procedures. There was a lack of that data,” Dr. Lin, chief of urologic oncology at the University of Washington, Seattle, said in an interview. He said the literature consists mainly of systematic single-center reviews, rather than multicenter randomized trials.

But Hendrik Van Poppel, MD, policy chief for the EAU, said that in Europe, transrectal biopsies are now considered “medical malpractice.”

Philip Cornford, MD, associate professor of urology at the University of Liverpool, England, and chair of the prostate biopsy guidelines panel for the EAU, said the society in 2021 concluded that the transperineal approach is the preferred one.

The EAU stated that transperineal prostate biopsies should be performed “due to the lower risk of infectious complications.” The EAU described the evidence as strong: A meta-analysis of seven studies that included 1,330 patients showed that for patients undergoing transperineal biopsy, infectious complications were significantly reduced.

Dr. Cornford said in essence, the EAU made its decision out of concern about infections, whereas the AUA and SUO based their decision on the ability of the methods to detect cancer.

Advocates for transperineal procedures cite several studies that show that the rate of infection, including sepsis, with such biopsies is virtually zero.

However, Dr. Lin noted that the committee said existing data on infection did not support this position. He also cited a “a fairly compelling” single-center randomized study with 750 patients that showed no difference in infection rates. The study was presented at the AUA meeting.
 

Agents of death and destruction?

Badar Mian, MD, professor of surgery at Albany (N.Y.) Medical College, who led the study, told an AUA session that urology has been trapped in an “echo chamber” regarding the relative safety of biopsies.

Clinicians hear “loud proclamations, which get repeated and magnified, that there is a real zero risk of complications after transperineal biopsies as compared to the horrendous 5% to 10% or higher rate of transrectal biopsy complications and that you, with your transrectal biopsies, are the cause of death and destruction all around,” Dr. Mian said. “Well, if you step out of the echo chamber, what you’ll find is that the accurate complications amongst the two procedures are not that dramatically different, much less dramatic than what you’ve been told to believe.”

The campaign to end transrectal biopsies in Europe started in 2018 with the death of a Norwegian man who experienced an infection after the procedure. Truls Bjerklund Johansen, MD, who’d performed the biopsy on the patient and who worked with the man’s daughter to change national practice, persuaded the EAU to look at the issue.

Advocates also say transperineal biopsies are better at detecting anterior and apical cancers.

“I would agree the data on cancer detection is less convincing, but that is not the basis of the EAU recommendation,” Dr. Cornford said.

Arvin George, MD, leads the transperineal biopsy program at the University of Michigan, Ann Arbor, and directs the transperineal training program at the AUA’s annual meeting. He said his course was sold out early and included about 60 trainees.

Dr. George said the new guideline statement “is not an unequivocal endorsement for transperineal biopsy as the preferred approach for diagnostic sampling but rather an acknowledgment of this approach as an alternative option.”

He said that although the new position statement should increase awareness of the transperineal approach in the United States, “without a strong recommendation, the guideline statement is unlikely to spark a large switch to the transperineal biopsy but rather supports the continued slow and steady adoption.”

Matthew Allaway, DO, founder of Perineologic, developer of the PrecisionPoint Transperineal Access System, said industry figures show that about 10% of the 1.5 million prostate biopsies performed in the United States annually are performed transperineally, a doubling in 2 years.

Jeremy Grummet, MD, clinical professor of urology at Monash University, Melbourne, and leader of the TREXIT (Transperineal Exit) movement to abandon transrectal procedures, said the AUA guidelines are biased toward “physician convenience.”
 

Lack of training

The AUA said another reason it did not endorse the transperineal approach was that currently, American urologists lack training and experience with transperineal procedures.

Dr. Grummet blamed major medical centers for any gap in the familiarity of clinicians with transperineal biopsies, which have been available for more than a decade.

“It is incumbent on the leaders of urology departments globally to ensure that their colleagues are trained in transperineal biopsy and have access to the appropriate equipment,” he said in an interview. “Lack of training didn’t seem to prevent the rapid uptake of robotic prostatectomy – a far more complex procedure.”

The authors have disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

CHICAGO - The American Urological Association and the Society of Urologic Oncology (SUO) for the first time have taken a position on the type of biopsy men with prostate lesions should undergo, endorsing both transperineal and transrectal biopsy instead of choosing one over the other.

The new guidelines, issued at the annual meeting of the American Urological Association, contrast with 2021 recommendations from the European Association of Urologists (EAU), which regard the transperineal approach as superior to and safer than the transrectal approach.

The new guidelines state: “Clinicians may use either a transrectal or transperineal biopsy route when performing a biopsy. (Conditional Recommendation; Evidence Level: Grade C).” Grade C is the lowest grade of acceptance the guideline committee could issue, according to Daniel Lin, MD, vice-chair of the AUA guideline panel.

“The AUA looked at all the higher-level data comparing the two procedures. There was a lack of that data,” Dr. Lin, chief of urologic oncology at the University of Washington, Seattle, said in an interview. He said the literature consists mainly of systematic single-center reviews, rather than multicenter randomized trials.

But Hendrik Van Poppel, MD, policy chief for the EAU, said that in Europe, transrectal biopsies are now considered “medical malpractice.”

Philip Cornford, MD, associate professor of urology at the University of Liverpool, England, and chair of the prostate biopsy guidelines panel for the EAU, said the society in 2021 concluded that the transperineal approach is the preferred one.

The EAU stated that transperineal prostate biopsies should be performed “due to the lower risk of infectious complications.” The EAU described the evidence as strong: A meta-analysis of seven studies that included 1,330 patients showed that for patients undergoing transperineal biopsy, infectious complications were significantly reduced.

Dr. Cornford said in essence, the EAU made its decision out of concern about infections, whereas the AUA and SUO based their decision on the ability of the methods to detect cancer.

Advocates for transperineal procedures cite several studies that show that the rate of infection, including sepsis, with such biopsies is virtually zero.

However, Dr. Lin noted that the committee said existing data on infection did not support this position. He also cited a “a fairly compelling” single-center randomized study with 750 patients that showed no difference in infection rates. The study was presented at the AUA meeting.
 

Agents of death and destruction?

Badar Mian, MD, professor of surgery at Albany (N.Y.) Medical College, who led the study, told an AUA session that urology has been trapped in an “echo chamber” regarding the relative safety of biopsies.

Clinicians hear “loud proclamations, which get repeated and magnified, that there is a real zero risk of complications after transperineal biopsies as compared to the horrendous 5% to 10% or higher rate of transrectal biopsy complications and that you, with your transrectal biopsies, are the cause of death and destruction all around,” Dr. Mian said. “Well, if you step out of the echo chamber, what you’ll find is that the accurate complications amongst the two procedures are not that dramatically different, much less dramatic than what you’ve been told to believe.”

The campaign to end transrectal biopsies in Europe started in 2018 with the death of a Norwegian man who experienced an infection after the procedure. Truls Bjerklund Johansen, MD, who’d performed the biopsy on the patient and who worked with the man’s daughter to change national practice, persuaded the EAU to look at the issue.

Advocates also say transperineal biopsies are better at detecting anterior and apical cancers.

“I would agree the data on cancer detection is less convincing, but that is not the basis of the EAU recommendation,” Dr. Cornford said.

Arvin George, MD, leads the transperineal biopsy program at the University of Michigan, Ann Arbor, and directs the transperineal training program at the AUA’s annual meeting. He said his course was sold out early and included about 60 trainees.

Dr. George said the new guideline statement “is not an unequivocal endorsement for transperineal biopsy as the preferred approach for diagnostic sampling but rather an acknowledgment of this approach as an alternative option.”

He said that although the new position statement should increase awareness of the transperineal approach in the United States, “without a strong recommendation, the guideline statement is unlikely to spark a large switch to the transperineal biopsy but rather supports the continued slow and steady adoption.”

Matthew Allaway, DO, founder of Perineologic, developer of the PrecisionPoint Transperineal Access System, said industry figures show that about 10% of the 1.5 million prostate biopsies performed in the United States annually are performed transperineally, a doubling in 2 years.

Jeremy Grummet, MD, clinical professor of urology at Monash University, Melbourne, and leader of the TREXIT (Transperineal Exit) movement to abandon transrectal procedures, said the AUA guidelines are biased toward “physician convenience.”
 

Lack of training

The AUA said another reason it did not endorse the transperineal approach was that currently, American urologists lack training and experience with transperineal procedures.

Dr. Grummet blamed major medical centers for any gap in the familiarity of clinicians with transperineal biopsies, which have been available for more than a decade.

“It is incumbent on the leaders of urology departments globally to ensure that their colleagues are trained in transperineal biopsy and have access to the appropriate equipment,” he said in an interview. “Lack of training didn’t seem to prevent the rapid uptake of robotic prostatectomy – a far more complex procedure.”

The authors have disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved avapritinib (AYVAKIT, Blueprint Medicines) for the treatment of adults with indolent systemic mastocytosis. The new approval, which expands use of the drug to patients with indolent systemic mastocytosis, represents the “first and only approved medicine” to treat this disease, according to the company press statement.

Avapritinib, a selective KIT mutation-targeted tyrosine kinase inhibitor, was approved in 2021 to treat advanced systemic mastocytosis, a rare and potentially fatal hematologic disorder. Nonadvanced forms include indolent or smoldering disease; advanced disease can progress to leukemia. The expanded approval now covers patients with indolent disease, which represents the majority of patients with systemic mastocytosis.

The drug is also approved for adults with unresectable or metastatic GIST that harbors a platelet-derived growth factor receptor alpha exon 18 mutation.

The approval is based on data from the phase 2 PIONEER trial. In the trial, 222 patients with moderate to severe indolent, systemic mastocytosis* were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care.

The findings, published in February, revealed that patients who received avapritinib experienced significantly greater improvements in total symptom scores at 24 weeks (–15.6 vs. –9.2 for control patients). Significantly more patients in the avapritinib arm achieved greater than or equal to 50% reductions in serum tryptase (54% vs. 0%), bone marrow mast cell aggregates (53% vs. 23%), and KIT D816V variant allele fraction (68% vs. 6%).

Most adverse reactions were mild to moderate in severity and included eye edema, dizziness, peripheral edema, and flushing. Fewer than 1% of patients discontinued treatment because of serious adverse reactions.

“People with indolent systemic mastocytosis are significantly impacted by their disease symptoms, and many individuals self-isolate at home to protect against unpredictable external triggers,” Judith Kain Emmel, board chair of the Mast Cell Disease Society, said in the company press release. “Today’s approval is a historic moment for the [systemic mastocytosis] community and offers new hope for patients and their families.

A version of this article first appeared on Medscape.com.

Correction, 5/23/23: An earlier version of this article mischaracterized these patients' conditions. They had moderate to severe indolent, systemic mastocytosis.

The U.S. Food and Drug Administration has approved avapritinib (AYVAKIT, Blueprint Medicines) for the treatment of adults with indolent systemic mastocytosis. The new approval, which expands use of the drug to patients with indolent systemic mastocytosis, represents the “first and only approved medicine” to treat this disease, according to the company press statement.

Avapritinib, a selective KIT mutation-targeted tyrosine kinase inhibitor, was approved in 2021 to treat advanced systemic mastocytosis, a rare and potentially fatal hematologic disorder. Nonadvanced forms include indolent or smoldering disease; advanced disease can progress to leukemia. The expanded approval now covers patients with indolent disease, which represents the majority of patients with systemic mastocytosis.

The drug is also approved for adults with unresectable or metastatic GIST that harbors a platelet-derived growth factor receptor alpha exon 18 mutation.

The approval is based on data from the phase 2 PIONEER trial. In the trial, 222 patients with moderate to severe indolent, systemic mastocytosis* were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care.

The findings, published in February, revealed that patients who received avapritinib experienced significantly greater improvements in total symptom scores at 24 weeks (–15.6 vs. –9.2 for control patients). Significantly more patients in the avapritinib arm achieved greater than or equal to 50% reductions in serum tryptase (54% vs. 0%), bone marrow mast cell aggregates (53% vs. 23%), and KIT D816V variant allele fraction (68% vs. 6%).

Most adverse reactions were mild to moderate in severity and included eye edema, dizziness, peripheral edema, and flushing. Fewer than 1% of patients discontinued treatment because of serious adverse reactions.

“People with indolent systemic mastocytosis are significantly impacted by their disease symptoms, and many individuals self-isolate at home to protect against unpredictable external triggers,” Judith Kain Emmel, board chair of the Mast Cell Disease Society, said in the company press release. “Today’s approval is a historic moment for the [systemic mastocytosis] community and offers new hope for patients and their families.

A version of this article first appeared on Medscape.com.

Correction, 5/23/23: An earlier version of this article mischaracterized these patients' conditions. They had moderate to severe indolent, systemic mastocytosis.

The U.S. Food and Drug Administration has approved avapritinib (AYVAKIT, Blueprint Medicines) for the treatment of adults with indolent systemic mastocytosis. The new approval, which expands use of the drug to patients with indolent systemic mastocytosis, represents the “first and only approved medicine” to treat this disease, according to the company press statement.

Avapritinib, a selective KIT mutation-targeted tyrosine kinase inhibitor, was approved in 2021 to treat advanced systemic mastocytosis, a rare and potentially fatal hematologic disorder. Nonadvanced forms include indolent or smoldering disease; advanced disease can progress to leukemia. The expanded approval now covers patients with indolent disease, which represents the majority of patients with systemic mastocytosis.

The drug is also approved for adults with unresectable or metastatic GIST that harbors a platelet-derived growth factor receptor alpha exon 18 mutation.

The approval is based on data from the phase 2 PIONEER trial. In the trial, 222 patients with moderate to severe indolent, systemic mastocytosis* were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care.

The findings, published in February, revealed that patients who received avapritinib experienced significantly greater improvements in total symptom scores at 24 weeks (–15.6 vs. –9.2 for control patients). Significantly more patients in the avapritinib arm achieved greater than or equal to 50% reductions in serum tryptase (54% vs. 0%), bone marrow mast cell aggregates (53% vs. 23%), and KIT D816V variant allele fraction (68% vs. 6%).

Most adverse reactions were mild to moderate in severity and included eye edema, dizziness, peripheral edema, and flushing. Fewer than 1% of patients discontinued treatment because of serious adverse reactions.

“People with indolent systemic mastocytosis are significantly impacted by their disease symptoms, and many individuals self-isolate at home to protect against unpredictable external triggers,” Judith Kain Emmel, board chair of the Mast Cell Disease Society, said in the company press release. “Today’s approval is a historic moment for the [systemic mastocytosis] community and offers new hope for patients and their families.

A version of this article first appeared on Medscape.com.

Correction, 5/23/23: An earlier version of this article mischaracterized these patients' conditions. They had moderate to severe indolent, systemic mastocytosis.

Thrombophilia testing should be limited to specific circumstances, including when venous thromboembolism (VTE) is provoked by nonsurgical risk factors such as pregnancy or oral contraception use, according to new clinical practice guidelines released by the American Society of Hematology. Individuals with a family history of VTE and high-risk thrombophilia, and those with VTE at unusual body sites should also be tested, the guidelines panel agreed.

“These guidelines will potentially change practice – we know that providers and patients will make a shared treatment decision and we wanted to outline specific scenarios to guide that decision,” panel cochair and first author Saskia Middeldorp, MD, PhD, explained in a press release announcing the publication of the guidelines in Blood Advances.

Dr. Middeldorp is a professor of medicine and head of the department of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands.

The guidelines are the latest in an ASH series of VTE-related guidelines. ASH convened a multidisciplinary panel with clinical and methodological expertise to develop the guidelines, which were subject to public comment, and they “provide recommendations informed by case-based approaches and modeling to ensure the medical community can better diagnose and treat thrombophilia and people with the condition can make the best decisions for their care,” the press release explains.

Thrombophilia affects an estimated 10% of the population. Testing for the clotting disorder can be costly, and the use of testing to help guide treatment decisions is controversial.

“For decades there has been dispute about thrombophilia testing,” Dr. Middeldorp said. “We created a model about whether and when it would be useful to test for thrombophilia, and based on the model, we suggest it can be appropriate in [the specified] situations.

The panel agreed on 23 recommendations regarding thrombophilia testing and management. Most are based on “very low certainty” in the evidence because of modeling assumptions.

However, the panel agreed on a strong recommendation against testing the general population before starting combined oral contraceptives (COC), and a conditional recommendation for thrombophilia testing in:

• Patients with VTE associated with nonsurgical major transient or hormonal risk factors
• Patients with cerebral or splanchnic venous thrombosis in settings where anticoagulation would otherwise be discontinued
• Individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance related to the use of COC or hormone therapy
• Pregnant women with a family history of high-risk thrombophilia types
• Patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE

“In all other instances, we suggest not testing for thrombophilia,” said Dr. Middeldorp.

The ASH guidelines largely mirror those of existing guidelines from a number of other organizations, but the recommendation in favor of testing for thrombophilia in patients with VTE provoked by a nonsurgical major transient risk factor or associated with COCs, hormone therapy, pregnancy or postpartum is new and “may cause considerable discussion, as many currently view these VTE episodes as provoked and are generally inclined to use short-term anticoagulation for such patients,” the guideline authors wrote.

“It is important to note, however, that most guidelines or guidance statements on thrombophilia testing did not distinguish between major and minor provoking risk factors, which current science suggests is appropriate,” they added.

Another novel recommendation is the suggestion to test for hereditary thrombophilia to guide the use of thromboprophylaxis during systemic treatment in ambulatory patients with cancer who are at low or intermediate risk for VTE and who have a family history of VTE.

“This new recommendation should be seen as a new application of an established risk stratification approach,” they said.

Additional research is urgently needed, particularly “large implementation studies comparing the impact, in terms of outcomes rates, among management strategies involving or not involving thrombophilia testing,” they noted.

The guideline was wholly funded by ASH. Dr. Middeldorp reported having no conflicts of interest.

Thrombophilia testing should be limited to specific circumstances, including when venous thromboembolism (VTE) is provoked by nonsurgical risk factors such as pregnancy or oral contraception use, according to new clinical practice guidelines released by the American Society of Hematology. Individuals with a family history of VTE and high-risk thrombophilia, and those with VTE at unusual body sites should also be tested, the guidelines panel agreed.

“These guidelines will potentially change practice – we know that providers and patients will make a shared treatment decision and we wanted to outline specific scenarios to guide that decision,” panel cochair and first author Saskia Middeldorp, MD, PhD, explained in a press release announcing the publication of the guidelines in Blood Advances.

Dr. Middeldorp is a professor of medicine and head of the department of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands.

The guidelines are the latest in an ASH series of VTE-related guidelines. ASH convened a multidisciplinary panel with clinical and methodological expertise to develop the guidelines, which were subject to public comment, and they “provide recommendations informed by case-based approaches and modeling to ensure the medical community can better diagnose and treat thrombophilia and people with the condition can make the best decisions for their care,” the press release explains.

Thrombophilia affects an estimated 10% of the population. Testing for the clotting disorder can be costly, and the use of testing to help guide treatment decisions is controversial.

“For decades there has been dispute about thrombophilia testing,” Dr. Middeldorp said. “We created a model about whether and when it would be useful to test for thrombophilia, and based on the model, we suggest it can be appropriate in [the specified] situations.

The panel agreed on 23 recommendations regarding thrombophilia testing and management. Most are based on “very low certainty” in the evidence because of modeling assumptions.

However, the panel agreed on a strong recommendation against testing the general population before starting combined oral contraceptives (COC), and a conditional recommendation for thrombophilia testing in:

• Patients with VTE associated with nonsurgical major transient or hormonal risk factors
• Patients with cerebral or splanchnic venous thrombosis in settings where anticoagulation would otherwise be discontinued
• Individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance related to the use of COC or hormone therapy
• Pregnant women with a family history of high-risk thrombophilia types
• Patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE

“In all other instances, we suggest not testing for thrombophilia,” said Dr. Middeldorp.

The ASH guidelines largely mirror those of existing guidelines from a number of other organizations, but the recommendation in favor of testing for thrombophilia in patients with VTE provoked by a nonsurgical major transient risk factor or associated with COCs, hormone therapy, pregnancy or postpartum is new and “may cause considerable discussion, as many currently view these VTE episodes as provoked and are generally inclined to use short-term anticoagulation for such patients,” the guideline authors wrote.

“It is important to note, however, that most guidelines or guidance statements on thrombophilia testing did not distinguish between major and minor provoking risk factors, which current science suggests is appropriate,” they added.

Another novel recommendation is the suggestion to test for hereditary thrombophilia to guide the use of thromboprophylaxis during systemic treatment in ambulatory patients with cancer who are at low or intermediate risk for VTE and who have a family history of VTE.

“This new recommendation should be seen as a new application of an established risk stratification approach,” they said.

Additional research is urgently needed, particularly “large implementation studies comparing the impact, in terms of outcomes rates, among management strategies involving or not involving thrombophilia testing,” they noted.

The guideline was wholly funded by ASH. Dr. Middeldorp reported having no conflicts of interest.

Thrombophilia testing should be limited to specific circumstances, including when venous thromboembolism (VTE) is provoked by nonsurgical risk factors such as pregnancy or oral contraception use, according to new clinical practice guidelines released by the American Society of Hematology. Individuals with a family history of VTE and high-risk thrombophilia, and those with VTE at unusual body sites should also be tested, the guidelines panel agreed.

“These guidelines will potentially change practice – we know that providers and patients will make a shared treatment decision and we wanted to outline specific scenarios to guide that decision,” panel cochair and first author Saskia Middeldorp, MD, PhD, explained in a press release announcing the publication of the guidelines in Blood Advances.

Dr. Middeldorp is a professor of medicine and head of the department of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands.

The guidelines are the latest in an ASH series of VTE-related guidelines. ASH convened a multidisciplinary panel with clinical and methodological expertise to develop the guidelines, which were subject to public comment, and they “provide recommendations informed by case-based approaches and modeling to ensure the medical community can better diagnose and treat thrombophilia and people with the condition can make the best decisions for their care,” the press release explains.

Thrombophilia affects an estimated 10% of the population. Testing for the clotting disorder can be costly, and the use of testing to help guide treatment decisions is controversial.

“For decades there has been dispute about thrombophilia testing,” Dr. Middeldorp said. “We created a model about whether and when it would be useful to test for thrombophilia, and based on the model, we suggest it can be appropriate in [the specified] situations.

The panel agreed on 23 recommendations regarding thrombophilia testing and management. Most are based on “very low certainty” in the evidence because of modeling assumptions.

However, the panel agreed on a strong recommendation against testing the general population before starting combined oral contraceptives (COC), and a conditional recommendation for thrombophilia testing in:

• Patients with VTE associated with nonsurgical major transient or hormonal risk factors
• Patients with cerebral or splanchnic venous thrombosis in settings where anticoagulation would otherwise be discontinued
• Individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance related to the use of COC or hormone therapy
• Pregnant women with a family history of high-risk thrombophilia types
• Patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE

“In all other instances, we suggest not testing for thrombophilia,” said Dr. Middeldorp.

The ASH guidelines largely mirror those of existing guidelines from a number of other organizations, but the recommendation in favor of testing for thrombophilia in patients with VTE provoked by a nonsurgical major transient risk factor or associated with COCs, hormone therapy, pregnancy or postpartum is new and “may cause considerable discussion, as many currently view these VTE episodes as provoked and are generally inclined to use short-term anticoagulation for such patients,” the guideline authors wrote.

“It is important to note, however, that most guidelines or guidance statements on thrombophilia testing did not distinguish between major and minor provoking risk factors, which current science suggests is appropriate,” they added.

Another novel recommendation is the suggestion to test for hereditary thrombophilia to guide the use of thromboprophylaxis during systemic treatment in ambulatory patients with cancer who are at low or intermediate risk for VTE and who have a family history of VTE.

“This new recommendation should be seen as a new application of an established risk stratification approach,” they said.

Additional research is urgently needed, particularly “large implementation studies comparing the impact, in terms of outcomes rates, among management strategies involving or not involving thrombophilia testing,” they noted.

The guideline was wholly funded by ASH. Dr. Middeldorp reported having no conflicts of interest.

In a sign of the power of combination therapy for high-risk chronic lymphocytic leukemia (CLL), a small new study showed that patients were more likely to reach undetectable measurable residual disease (U-MRD) when they added venetoclax to their drug regimen after a year or more of taking ibrutinib.

Of 45 patients, 57% reached U-MRD at 12 months, and 55% reached complete remission, according to the study, published in Leukemia.

By adding venetoclax, “you can get very deep remissions in high-risk patients with ibrutinib,” lead author Philip A. Thompson, MBBS, a hematologist-oncologist with the University of Melbourne and Peter MacCallum Cancer Center, also in Melbourne, said in an interview. “This is a significant advance for really high-risk patients.”

According to Dr. Thompson, Bruton’s tyrosine kinase inhibitors like ibrutinib have revolutionized the treatment of high-risk CLL by forcing the disease into remission for several years and allowing patients to avoid stem cell transplants. “But the drug doesn’t eradicate the disease,” he said, “so eventually these patients develop progression.”

The current hope, he said, is to use a combination therapy like ibrutinib and venetoclax to send CLL into remission with lower chance of drug resistance and then allow patients to stop taking the medications.

Previous research has supported the combination of ibrutinib and venetoclax in CLL in the frontline setting, and the European Commission approved it in 2022 for that use. But “ours is the first [study] that looked at patients who’ve been on ibrutinib for a long time and added venetoclax,” Dr. Thompson said. In some cases, he said, patients in the study had been on ibrutinib for several years.

For the new study, researchers at the University of Texas MD Anderson Cancer Center in Houston – where Dr. Thompson used to work – tracked 45 patients (average age, 68.5 years; 51-80 years) with CLL or small lymphocytic lymphoma who had MRD but no clinical disease progression. They all had at least 1 high-risk feature such as a mutated TP53. They’d been on ibrutinib for a median of 32 months (12-73 months), and two were in complete remission but with MRD.

An intention-to-treat analysis found that 71% reached U-MRD when they finished taking venetoclax. “We were actually pleasantly surprised by the high rate of undetectable MRD,” Dr. Thompson said.

At a median 41-month follow-up, 11% of patients had progressed, but none had died of CLL or Richter transformation, a deadly complication of CLL. “The main side effects were neutropenia and diarrhea, which we were manageable,” Dr. Thompson said.

It’s not clear why the drug combination is especially effective, he said, but it may be because the medications are synergistic. According to the National Cancer Institute, synergy in medicine refers to “the interaction of two or more drugs when their combined effect is greater than the sum of the effects seen when each drug is given alone.”

The findings suggest that “you can get deep remissions in high-risk patients with ibrutinib and venetoclax with very with good tolerability and very low risk of on-treatment progression,” Dr. Thompson said. “We don’t yet have enough progression events to talk about retreatment data, but we do feel that retreatment with Bruton’s tyrosine kinase inhibitors – plus or minus venetoclax – will be successful in the vast majority of patients.”

The combination can be given off label in the United States, Dr. Thompson added. As for expense, adding venetoclax will double the cost of ibrutinib. The two drugs are some of the most expensive medications in the world. But patients will save money if they can stop therapy when they reach remission.

In an interview, hematologist-oncologist Kerry A. Rogers, MD, of Ohio State University, Columbus, who is not involved with the study, praised the research: “While small, this study does say quite a bit about this as a strategy to help people discontinue ibrutinib prior to resistance developing.”

She noted that Bruton’s tyrosine kinase inhibitors “are generally given as a continuous monotherapy, and venetoclax is usually given for a fixed duration in combination with an anti-CD20 antibody.”

Going forward, she said, “the fact that the study was in high-risk patients who have the most to gain from such a combination suggests that similar or better rates of undetectable minimal residual disease might be seen in non–high-risk groups. Additional follow-up should be reported as well as use of this strategy in a larger group of patients before this should be considered a standard approach.”

AbbVie funding the study and provided study drugs. MD Anderson Cancer Center conducted the study and discloses funding from the National Cancer Institute. Dr. Thompson reported ties with AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, BeiGene, and Genentech. The other study authors reported multiple disclosures. Dr. Rogers disclosed relationships with Genentech, AbbVie, Novartis, Janssen, Pharmacyclics, BeiGene, Lilly, and AstraZeneca.

In a sign of the power of combination therapy for high-risk chronic lymphocytic leukemia (CLL), a small new study showed that patients were more likely to reach undetectable measurable residual disease (U-MRD) when they added venetoclax to their drug regimen after a year or more of taking ibrutinib.

Of 45 patients, 57% reached U-MRD at 12 months, and 55% reached complete remission, according to the study, published in Leukemia.

By adding venetoclax, “you can get very deep remissions in high-risk patients with ibrutinib,” lead author Philip A. Thompson, MBBS, a hematologist-oncologist with the University of Melbourne and Peter MacCallum Cancer Center, also in Melbourne, said in an interview. “This is a significant advance for really high-risk patients.”

According to Dr. Thompson, Bruton’s tyrosine kinase inhibitors like ibrutinib have revolutionized the treatment of high-risk CLL by forcing the disease into remission for several years and allowing patients to avoid stem cell transplants. “But the drug doesn’t eradicate the disease,” he said, “so eventually these patients develop progression.”

The current hope, he said, is to use a combination therapy like ibrutinib and venetoclax to send CLL into remission with lower chance of drug resistance and then allow patients to stop taking the medications.

Previous research has supported the combination of ibrutinib and venetoclax in CLL in the frontline setting, and the European Commission approved it in 2022 for that use. But “ours is the first [study] that looked at patients who’ve been on ibrutinib for a long time and added venetoclax,” Dr. Thompson said. In some cases, he said, patients in the study had been on ibrutinib for several years.

For the new study, researchers at the University of Texas MD Anderson Cancer Center in Houston – where Dr. Thompson used to work – tracked 45 patients (average age, 68.5 years; 51-80 years) with CLL or small lymphocytic lymphoma who had MRD but no clinical disease progression. They all had at least 1 high-risk feature such as a mutated TP53. They’d been on ibrutinib for a median of 32 months (12-73 months), and two were in complete remission but with MRD.

An intention-to-treat analysis found that 71% reached U-MRD when they finished taking venetoclax. “We were actually pleasantly surprised by the high rate of undetectable MRD,” Dr. Thompson said.

At a median 41-month follow-up, 11% of patients had progressed, but none had died of CLL or Richter transformation, a deadly complication of CLL. “The main side effects were neutropenia and diarrhea, which we were manageable,” Dr. Thompson said.

It’s not clear why the drug combination is especially effective, he said, but it may be because the medications are synergistic. According to the National Cancer Institute, synergy in medicine refers to “the interaction of two or more drugs when their combined effect is greater than the sum of the effects seen when each drug is given alone.”

The findings suggest that “you can get deep remissions in high-risk patients with ibrutinib and venetoclax with very with good tolerability and very low risk of on-treatment progression,” Dr. Thompson said. “We don’t yet have enough progression events to talk about retreatment data, but we do feel that retreatment with Bruton’s tyrosine kinase inhibitors – plus or minus venetoclax – will be successful in the vast majority of patients.”

The combination can be given off label in the United States, Dr. Thompson added. As for expense, adding venetoclax will double the cost of ibrutinib. The two drugs are some of the most expensive medications in the world. But patients will save money if they can stop therapy when they reach remission.

In an interview, hematologist-oncologist Kerry A. Rogers, MD, of Ohio State University, Columbus, who is not involved with the study, praised the research: “While small, this study does say quite a bit about this as a strategy to help people discontinue ibrutinib prior to resistance developing.”

She noted that Bruton’s tyrosine kinase inhibitors “are generally given as a continuous monotherapy, and venetoclax is usually given for a fixed duration in combination with an anti-CD20 antibody.”

Going forward, she said, “the fact that the study was in high-risk patients who have the most to gain from such a combination suggests that similar or better rates of undetectable minimal residual disease might be seen in non–high-risk groups. Additional follow-up should be reported as well as use of this strategy in a larger group of patients before this should be considered a standard approach.”

AbbVie funding the study and provided study drugs. MD Anderson Cancer Center conducted the study and discloses funding from the National Cancer Institute. Dr. Thompson reported ties with AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, BeiGene, and Genentech. The other study authors reported multiple disclosures. Dr. Rogers disclosed relationships with Genentech, AbbVie, Novartis, Janssen, Pharmacyclics, BeiGene, Lilly, and AstraZeneca.

In a sign of the power of combination therapy for high-risk chronic lymphocytic leukemia (CLL), a small new study showed that patients were more likely to reach undetectable measurable residual disease (U-MRD) when they added venetoclax to their drug regimen after a year or more of taking ibrutinib.

Of 45 patients, 57% reached U-MRD at 12 months, and 55% reached complete remission, according to the study, published in Leukemia.

By adding venetoclax, “you can get very deep remissions in high-risk patients with ibrutinib,” lead author Philip A. Thompson, MBBS, a hematologist-oncologist with the University of Melbourne and Peter MacCallum Cancer Center, also in Melbourne, said in an interview. “This is a significant advance for really high-risk patients.”

According to Dr. Thompson, Bruton’s tyrosine kinase inhibitors like ibrutinib have revolutionized the treatment of high-risk CLL by forcing the disease into remission for several years and allowing patients to avoid stem cell transplants. “But the drug doesn’t eradicate the disease,” he said, “so eventually these patients develop progression.”

The current hope, he said, is to use a combination therapy like ibrutinib and venetoclax to send CLL into remission with lower chance of drug resistance and then allow patients to stop taking the medications.

Previous research has supported the combination of ibrutinib and venetoclax in CLL in the frontline setting, and the European Commission approved it in 2022 for that use. But “ours is the first [study] that looked at patients who’ve been on ibrutinib for a long time and added venetoclax,” Dr. Thompson said. In some cases, he said, patients in the study had been on ibrutinib for several years.

For the new study, researchers at the University of Texas MD Anderson Cancer Center in Houston – where Dr. Thompson used to work – tracked 45 patients (average age, 68.5 years; 51-80 years) with CLL or small lymphocytic lymphoma who had MRD but no clinical disease progression. They all had at least 1 high-risk feature such as a mutated TP53. They’d been on ibrutinib for a median of 32 months (12-73 months), and two were in complete remission but with MRD.

An intention-to-treat analysis found that 71% reached U-MRD when they finished taking venetoclax. “We were actually pleasantly surprised by the high rate of undetectable MRD,” Dr. Thompson said.

At a median 41-month follow-up, 11% of patients had progressed, but none had died of CLL or Richter transformation, a deadly complication of CLL. “The main side effects were neutropenia and diarrhea, which we were manageable,” Dr. Thompson said.

It’s not clear why the drug combination is especially effective, he said, but it may be because the medications are synergistic. According to the National Cancer Institute, synergy in medicine refers to “the interaction of two or more drugs when their combined effect is greater than the sum of the effects seen when each drug is given alone.”

The findings suggest that “you can get deep remissions in high-risk patients with ibrutinib and venetoclax with very with good tolerability and very low risk of on-treatment progression,” Dr. Thompson said. “We don’t yet have enough progression events to talk about retreatment data, but we do feel that retreatment with Bruton’s tyrosine kinase inhibitors – plus or minus venetoclax – will be successful in the vast majority of patients.”

The combination can be given off label in the United States, Dr. Thompson added. As for expense, adding venetoclax will double the cost of ibrutinib. The two drugs are some of the most expensive medications in the world. But patients will save money if they can stop therapy when they reach remission.

In an interview, hematologist-oncologist Kerry A. Rogers, MD, of Ohio State University, Columbus, who is not involved with the study, praised the research: “While small, this study does say quite a bit about this as a strategy to help people discontinue ibrutinib prior to resistance developing.”

She noted that Bruton’s tyrosine kinase inhibitors “are generally given as a continuous monotherapy, and venetoclax is usually given for a fixed duration in combination with an anti-CD20 antibody.”

Going forward, she said, “the fact that the study was in high-risk patients who have the most to gain from such a combination suggests that similar or better rates of undetectable minimal residual disease might be seen in non–high-risk groups. Additional follow-up should be reported as well as use of this strategy in a larger group of patients before this should be considered a standard approach.”

AbbVie funding the study and provided study drugs. MD Anderson Cancer Center conducted the study and discloses funding from the National Cancer Institute. Dr. Thompson reported ties with AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, BeiGene, and Genentech. The other study authors reported multiple disclosures. Dr. Rogers disclosed relationships with Genentech, AbbVie, Novartis, Janssen, Pharmacyclics, BeiGene, Lilly, and AstraZeneca.

The U.S. Food and Drug Administration approved epcoritamab-bysp (Epkinly, AbbVie and Genmab) today for adults with relapsed/refractory diffuse large B-cell lymphoma following at least two lines of systemic therapy. This includes patients with DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma.

Epcoritamab is the first subcutaneous bispecific antibody approved for the indication. The biologic simultaneously binds CD3 on cytotoxic T cells to CD20 on lymphomic B cells, inducing T-cell mediated destruction.

“Together with our partner, AbbVie, we recognize the unmet need for safe, effective, and accessible treatments for patients with B-cell malignancies and we believe that epcoritamab has the potential to become a core therapy in this patient population,” Jan van de Winkel, PhD, CEO of Genmab, said in a press release announcing the FDA’s acceptance of its biologic licensing application in November 2022.

A potential competitor, Roche’s bispecific antibody mosunetuzumab (Lunsumio), was approved in December 2022. Mosunetuzumab has the same mechanism of action as epcoritamab but is indicated for relapsed or refractory follicular lymphoma after at least two lines of systemic therapy. A phase 3 trial is currently underway exploring epcoritamab for relapsed or refractory follicular lymphoma as part of combination therapy.

The current approval was based on the open-label phase 2 EPCORE NHL-1 trial conducted by AbbVie and Genmab. The trial’s efficacy population included 148 adults with relapsed or refractory CD20+ large B-cell lymphoma who had received at least two prior lines of therapy, including anti-CD20 therapies. Almost 40% had undergone CAR-T cell therapy.

Epcoritamab was administered initially once weekly, then every 2 weeks, and then every 4 weeks until disease progression or unacceptable toxicity. The trial had no comparator arm.

At a median follow-up of 10.7 months, the overall response rate was 61% and the complete response rate was 38%. At a median follow-up of 9.8 months among responders, the median duration of response was 15.6 months.

The prescribing information comes with a boxed warning for serious or life-threatening cytokine release syndrome and life-threatening or fatal immune effector cell–associated neurotoxicity syndrome. Warnings and precautions include infections and cytopenias.

Among the 157 patients who received epcoritamab in the trial at the recommended dose, grade 1-3 cytokine release syndrome occurred in 51%, immune effector cell–associated neurotoxicity syndrome occurred in 6% (with one fatal case), and 15% experienced serious infections.

The most common grade 3 or 4 events included neutropenia (14.6%), anemia (10.2%), and thrombocytopenia (5.7%).

The FDA recommends epcoritamab be administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity.

The FDA also noted that “this indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”
 

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration approved epcoritamab-bysp (Epkinly, AbbVie and Genmab) today for adults with relapsed/refractory diffuse large B-cell lymphoma following at least two lines of systemic therapy. This includes patients with DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma.

Epcoritamab is the first subcutaneous bispecific antibody approved for the indication. The biologic simultaneously binds CD3 on cytotoxic T cells to CD20 on lymphomic B cells, inducing T-cell mediated destruction.

“Together with our partner, AbbVie, we recognize the unmet need for safe, effective, and accessible treatments for patients with B-cell malignancies and we believe that epcoritamab has the potential to become a core therapy in this patient population,” Jan van de Winkel, PhD, CEO of Genmab, said in a press release announcing the FDA’s acceptance of its biologic licensing application in November 2022.

A potential competitor, Roche’s bispecific antibody mosunetuzumab (Lunsumio), was approved in December 2022. Mosunetuzumab has the same mechanism of action as epcoritamab but is indicated for relapsed or refractory follicular lymphoma after at least two lines of systemic therapy. A phase 3 trial is currently underway exploring epcoritamab for relapsed or refractory follicular lymphoma as part of combination therapy.

The current approval was based on the open-label phase 2 EPCORE NHL-1 trial conducted by AbbVie and Genmab. The trial’s efficacy population included 148 adults with relapsed or refractory CD20+ large B-cell lymphoma who had received at least two prior lines of therapy, including anti-CD20 therapies. Almost 40% had undergone CAR-T cell therapy.

Epcoritamab was administered initially once weekly, then every 2 weeks, and then every 4 weeks until disease progression or unacceptable toxicity. The trial had no comparator arm.

At a median follow-up of 10.7 months, the overall response rate was 61% and the complete response rate was 38%. At a median follow-up of 9.8 months among responders, the median duration of response was 15.6 months.

The prescribing information comes with a boxed warning for serious or life-threatening cytokine release syndrome and life-threatening or fatal immune effector cell–associated neurotoxicity syndrome. Warnings and precautions include infections and cytopenias.

Among the 157 patients who received epcoritamab in the trial at the recommended dose, grade 1-3 cytokine release syndrome occurred in 51%, immune effector cell–associated neurotoxicity syndrome occurred in 6% (with one fatal case), and 15% experienced serious infections.

The most common grade 3 or 4 events included neutropenia (14.6%), anemia (10.2%), and thrombocytopenia (5.7%).

The FDA recommends epcoritamab be administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity.

The FDA also noted that “this indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”
 

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration approved epcoritamab-bysp (Epkinly, AbbVie and Genmab) today for adults with relapsed/refractory diffuse large B-cell lymphoma following at least two lines of systemic therapy. This includes patients with DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma.

Epcoritamab is the first subcutaneous bispecific antibody approved for the indication. The biologic simultaneously binds CD3 on cytotoxic T cells to CD20 on lymphomic B cells, inducing T-cell mediated destruction.

“Together with our partner, AbbVie, we recognize the unmet need for safe, effective, and accessible treatments for patients with B-cell malignancies and we believe that epcoritamab has the potential to become a core therapy in this patient population,” Jan van de Winkel, PhD, CEO of Genmab, said in a press release announcing the FDA’s acceptance of its biologic licensing application in November 2022.

A potential competitor, Roche’s bispecific antibody mosunetuzumab (Lunsumio), was approved in December 2022. Mosunetuzumab has the same mechanism of action as epcoritamab but is indicated for relapsed or refractory follicular lymphoma after at least two lines of systemic therapy. A phase 3 trial is currently underway exploring epcoritamab for relapsed or refractory follicular lymphoma as part of combination therapy.

The current approval was based on the open-label phase 2 EPCORE NHL-1 trial conducted by AbbVie and Genmab. The trial’s efficacy population included 148 adults with relapsed or refractory CD20+ large B-cell lymphoma who had received at least two prior lines of therapy, including anti-CD20 therapies. Almost 40% had undergone CAR-T cell therapy.

Epcoritamab was administered initially once weekly, then every 2 weeks, and then every 4 weeks until disease progression or unacceptable toxicity. The trial had no comparator arm.

At a median follow-up of 10.7 months, the overall response rate was 61% and the complete response rate was 38%. At a median follow-up of 9.8 months among responders, the median duration of response was 15.6 months.

The prescribing information comes with a boxed warning for serious or life-threatening cytokine release syndrome and life-threatening or fatal immune effector cell–associated neurotoxicity syndrome. Warnings and precautions include infections and cytopenias.

Among the 157 patients who received epcoritamab in the trial at the recommended dose, grade 1-3 cytokine release syndrome occurred in 51%, immune effector cell–associated neurotoxicity syndrome occurred in 6% (with one fatal case), and 15% experienced serious infections.

The most common grade 3 or 4 events included neutropenia (14.6%), anemia (10.2%), and thrombocytopenia (5.7%).

The FDA recommends epcoritamab be administered subcutaneously in 28-day cycles until disease progression or unacceptable toxicity.

The FDA also noted that “this indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.”
 

A version of this article first appeared on Medscape.com.