Dr Harold Burstein, of the Dana-Farber Cancer Institute in Boston, Massachusetts, reports on studies in HR+/HER2- breast cancer presented at the 2022 San Antonio Breast Cancer Symposium. 

Dr Burstein reports on the phase 2 RIGHT Choice study, which is the first head-to-head comparison of endocrine therapy plus a CDK4/6 inhibitor vs chemotherapy for stage IV breast cancer. The results indicate that frontline therapy using the combination is superior to chemotherapy.  

Dr Burstein next comments on the phase 3 CAPItello-291 trial, which looked at a new AKT inhibitor, capivasertib. The study compared capivasertib plus fulvestrant vs fulvestrant alone and found that the combination provided meaningful improvements in progression-free survival. He then reports on the phase 2 SERENA-2 trial, which compared fulvestrant with camizestrant, an oral selective estrogen receptor degrader, in the second-line setting. The study showed that camizestrant was superior to fulvestrant.  

An update of the phase 3 monarchE trial showed an increasing benefit from adding abemaciclib to endocrine therapy in the adjuvant setting, regardless of the Ki-67 index. 

In closing, Dr Burstein discusses the POSITIVE trial, which indicated that endocrine therapy can be safely interrupted in women whose breast cancer is in remission and who are pursuing pregnancy.  

--

Harold J. Burstein, MD, PhD, Professor, Department of Medicine, Harvard Medical School; Medical Oncologist, Dana-Farber Cancer Institute, Boston, Massachusetts 

Harold J. Burstein, MD, PhD, has disclosed no relevant financial relationships. 

Dr Harold Burstein, of the Dana-Farber Cancer Institute in Boston, Massachusetts, reports on studies in HR+/HER2- breast cancer presented at the 2022 San Antonio Breast Cancer Symposium. 

Dr Burstein reports on the phase 2 RIGHT Choice study, which is the first head-to-head comparison of endocrine therapy plus a CDK4/6 inhibitor vs chemotherapy for stage IV breast cancer. The results indicate that frontline therapy using the combination is superior to chemotherapy.  

Dr Burstein next comments on the phase 3 CAPItello-291 trial, which looked at a new AKT inhibitor, capivasertib. The study compared capivasertib plus fulvestrant vs fulvestrant alone and found that the combination provided meaningful improvements in progression-free survival. He then reports on the phase 2 SERENA-2 trial, which compared fulvestrant with camizestrant, an oral selective estrogen receptor degrader, in the second-line setting. The study showed that camizestrant was superior to fulvestrant.  

An update of the phase 3 monarchE trial showed an increasing benefit from adding abemaciclib to endocrine therapy in the adjuvant setting, regardless of the Ki-67 index. 

In closing, Dr Burstein discusses the POSITIVE trial, which indicated that endocrine therapy can be safely interrupted in women whose breast cancer is in remission and who are pursuing pregnancy.  

--

Harold J. Burstein, MD, PhD, Professor, Department of Medicine, Harvard Medical School; Medical Oncologist, Dana-Farber Cancer Institute, Boston, Massachusetts 

Harold J. Burstein, MD, PhD, has disclosed no relevant financial relationships. 

Dr Harold Burstein, of the Dana-Farber Cancer Institute in Boston, Massachusetts, reports on studies in HR+/HER2- breast cancer presented at the 2022 San Antonio Breast Cancer Symposium. 

Dr Burstein reports on the phase 2 RIGHT Choice study, which is the first head-to-head comparison of endocrine therapy plus a CDK4/6 inhibitor vs chemotherapy for stage IV breast cancer. The results indicate that frontline therapy using the combination is superior to chemotherapy.  

Dr Burstein next comments on the phase 3 CAPItello-291 trial, which looked at a new AKT inhibitor, capivasertib. The study compared capivasertib plus fulvestrant vs fulvestrant alone and found that the combination provided meaningful improvements in progression-free survival. He then reports on the phase 2 SERENA-2 trial, which compared fulvestrant with camizestrant, an oral selective estrogen receptor degrader, in the second-line setting. The study showed that camizestrant was superior to fulvestrant.  

An update of the phase 3 monarchE trial showed an increasing benefit from adding abemaciclib to endocrine therapy in the adjuvant setting, regardless of the Ki-67 index. 

In closing, Dr Burstein discusses the POSITIVE trial, which indicated that endocrine therapy can be safely interrupted in women whose breast cancer is in remission and who are pursuing pregnancy.  

--

Harold J. Burstein, MD, PhD, Professor, Department of Medicine, Harvard Medical School; Medical Oncologist, Dana-Farber Cancer Institute, Boston, Massachusetts 

Harold J. Burstein, MD, PhD, has disclosed no relevant financial relationships. 

Breast cancer treatments have made great strides in recent years with significant reductions in overall mortality. However, the incidence of breast cancer has increased just slightly in recent years after a dip in the early 2000s.

“The good news is that mortality is decreasing, but it still remains high. We still have a long way to go to tackle this problem of breast cancer incidence as well as the number of deaths,” said Angela DeMichele, MD, co-leader of the breast cancer research program at the University of Pennsylvania’s Abramson Cancer Center. She participated in a session on obstacles in breast cancer treatment held in December at the San Antonio Breast Cancer Symposium. She joined other oncologists in outlining key challenges that need to be addressed to improve breast cancer diagnosis and treatment.

They highlighted six obstacles: The need for more prevention/early detection strategies; the underutilization of artificial intelligence; underuse of precision oncology such as targeted therapies; the need for innovation in clinical trials; a widening gap in cancer disparities; and the need to align incentives and funding for research collaboration, training, and retention.

Since 2012, the Food and Drug Administration has approved 20 new therapeutics to treat breast cancer. Nadia Harbeck, MD, PhD, director of the breast center at LMU University Hospital, Munich, said that the development of new therapies has in a way become a victim of its own success. Therapies and survival have improved, making it harder to compare novel therapies to the standard of care and prove a benefit. Treatment guidelines are changing so quickly that clinical trials are sometimes obsolete by the time they are published because of changes to the standard of care. That places a need on more real-world evidence that can be designed to be useful in the clinic, and AI can help here. “We need to convince regulators to act upon cleverly planned real world evidence analysis. You can randomize them, you can use registries, and you should also be able to change labels because of [new] data,” Dr. Harbeck said.

There are many risk factors that drive breast cancer, and it is very heterogeneous, said Christine Ambrosone, PhD, chair of the department of cancer prevention and control at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y. She called for identifying patients who are at risk for a poor prognosis, such as patients with hormone receptor–negative breast cancer, high-grade, and triple-negative breast cancer. Otherwise there is a risk of overtreatment of low-risk tumors, which could potentially be identified with new tools in precision oncology such as liquid biopsy tests, also known as multicancer early detection tests. These tests can detect cancers long before they become symptomatic. The first such test was launched this year and many more are in clinical trials.

Regina Barzilay, PhD, professor and expert in the use of artificial intelligence in health at the Massachusetts Institute of Technology, pointed out that machine learning is used in many fields, but hardly at all in breast cancer. It could be applied to data on biomarkers and other factors collected from retrospective analyses and clinical trials. She added that machine learning is often applied to biochemistry and single cell analysis of other tumor types, but rarely in breast cancer. “It is severely underutilized,” Dr. Barzilay said. One challenge is that researchers are not necessarily familiar with the techniques of machine learning and AI. Another issue is that breast cancer data are not easy to share and may not be readily available to AI researchers. “An investment in interchangeable data is crucially important,” she said.

Artificial intelligence could assist in identifying and modeling factors that contribute to cancer risk by teasing apart complicated relationships, such as the association between pregnancy, breastfeeding, and breast cancer risk. Pregnancy reduces the risk of hormone receptor–positive disease, but increases the risk of hormone receptor–negative disease.

Another key challenge is the underuse of “omics” technologies, which measure large scale patterns in biological characteristics such as gene variation or protein expression. That has roots in the history of breast cancer being considered as a separate entity from other solid tumors such as lung or pancreatic cancer. Fabrice André, MD, PhD, an oncologist with Gustave Roussy Cancer Center, France, emphasized that breast cancer shouldn’t be considered an entity when it’s metastatic. Instead, tumors should be defined by molecular characteristics they share. He anticipates a personalized medicine future where academic and industry groups collaborate to create an individualized therapy for patients based on genetic factors.
 

Access to therapies for all patients

Novel and effective therapies can make a difference only if patients have access to them, and a key obstacle to improving breast cancer care is racism and inequities in health care. “We have to acknowledge that there is racism in medicine. I think once we acknowledge that, then we can look at things in our practices that we need to change. We can think very broadly and look at things that perhaps disadvantage one population over another,” said Lori Pierce, MD, a radiation oncologist with the University of Michigan, Ann Arbor.

Dr. Pierce also emphasized the need to recruit more underrepresented groups to participate in clinical trials. For example, of six breast cancer clinical trials – for margetuximab (Margenza), sacituzumab govitecan (Trodelvy), tucatinib (Tukysa), trastuzumab deruxtecan (Enhertu), alpelisib (Piqray), and talazoparib (Talzenna), only a small percentage included Black, Asian, and Hispanic women. For trastuzumab deruxtecan, which is widely recognized as a best-in-class HER2-targeting antibody drug conjugate, 51% were White, 42% Asian, 6% Hispanic, and 3% Black. For sacituzumab govitecan, a blockbuster drug for triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer that disproportionately affects Black women, only 7% of women enrolled in clinical trials were Black. In clinical trials for margetuximab, approved to treat HER2-positive breast cancer, 80% of participants were White, 5% Black, 6% Asian, and 9% Hispanic.

There is a perception that minorities may be unwilling to participate in clinical trials, but that’s not true, according to Patty Spears, a research manager of the Patient Advocates for Research Council at the University of North Carolina. “We know that there are data that clearly show that patients will go on clinical trials at the same rate, whether they’re Black, White, Asian, or whatever. You have to be able to have them in your system and ask them to go on trial,” she said.

Another panelist told a personal anecdote to illustrate the point. Matthew Ellis, MD, PhD, recalled that he spent 13 years at Washington University in St. Louis, serving one of the more segregated cities in the United States. The city hospital closed, and Washington University and the Siteman Cancer Center signed a contract to treat the underserved population that was suddenly without a source of care. “Subsequent to that, we over-accrued relative to the population of African American patients. What that taught me is it’s nothing to do with the lack of willingness of African Americans to participate in clinical trials. Quite the opposite. It’s the question of access to clinical trials, access to great care, and not creating health care systems that segregate patients into places where they’re not getting access,” he said.

Breast cancer treatments have made great strides in recent years with significant reductions in overall mortality. However, the incidence of breast cancer has increased just slightly in recent years after a dip in the early 2000s.

“The good news is that mortality is decreasing, but it still remains high. We still have a long way to go to tackle this problem of breast cancer incidence as well as the number of deaths,” said Angela DeMichele, MD, co-leader of the breast cancer research program at the University of Pennsylvania’s Abramson Cancer Center. She participated in a session on obstacles in breast cancer treatment held in December at the San Antonio Breast Cancer Symposium. She joined other oncologists in outlining key challenges that need to be addressed to improve breast cancer diagnosis and treatment.

They highlighted six obstacles: The need for more prevention/early detection strategies; the underutilization of artificial intelligence; underuse of precision oncology such as targeted therapies; the need for innovation in clinical trials; a widening gap in cancer disparities; and the need to align incentives and funding for research collaboration, training, and retention.

Since 2012, the Food and Drug Administration has approved 20 new therapeutics to treat breast cancer. Nadia Harbeck, MD, PhD, director of the breast center at LMU University Hospital, Munich, said that the development of new therapies has in a way become a victim of its own success. Therapies and survival have improved, making it harder to compare novel therapies to the standard of care and prove a benefit. Treatment guidelines are changing so quickly that clinical trials are sometimes obsolete by the time they are published because of changes to the standard of care. That places a need on more real-world evidence that can be designed to be useful in the clinic, and AI can help here. “We need to convince regulators to act upon cleverly planned real world evidence analysis. You can randomize them, you can use registries, and you should also be able to change labels because of [new] data,” Dr. Harbeck said.

There are many risk factors that drive breast cancer, and it is very heterogeneous, said Christine Ambrosone, PhD, chair of the department of cancer prevention and control at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y. She called for identifying patients who are at risk for a poor prognosis, such as patients with hormone receptor–negative breast cancer, high-grade, and triple-negative breast cancer. Otherwise there is a risk of overtreatment of low-risk tumors, which could potentially be identified with new tools in precision oncology such as liquid biopsy tests, also known as multicancer early detection tests. These tests can detect cancers long before they become symptomatic. The first such test was launched this year and many more are in clinical trials.

Regina Barzilay, PhD, professor and expert in the use of artificial intelligence in health at the Massachusetts Institute of Technology, pointed out that machine learning is used in many fields, but hardly at all in breast cancer. It could be applied to data on biomarkers and other factors collected from retrospective analyses and clinical trials. She added that machine learning is often applied to biochemistry and single cell analysis of other tumor types, but rarely in breast cancer. “It is severely underutilized,” Dr. Barzilay said. One challenge is that researchers are not necessarily familiar with the techniques of machine learning and AI. Another issue is that breast cancer data are not easy to share and may not be readily available to AI researchers. “An investment in interchangeable data is crucially important,” she said.

Artificial intelligence could assist in identifying and modeling factors that contribute to cancer risk by teasing apart complicated relationships, such as the association between pregnancy, breastfeeding, and breast cancer risk. Pregnancy reduces the risk of hormone receptor–positive disease, but increases the risk of hormone receptor–negative disease.

Another key challenge is the underuse of “omics” technologies, which measure large scale patterns in biological characteristics such as gene variation or protein expression. That has roots in the history of breast cancer being considered as a separate entity from other solid tumors such as lung or pancreatic cancer. Fabrice André, MD, PhD, an oncologist with Gustave Roussy Cancer Center, France, emphasized that breast cancer shouldn’t be considered an entity when it’s metastatic. Instead, tumors should be defined by molecular characteristics they share. He anticipates a personalized medicine future where academic and industry groups collaborate to create an individualized therapy for patients based on genetic factors.
 

Access to therapies for all patients

Novel and effective therapies can make a difference only if patients have access to them, and a key obstacle to improving breast cancer care is racism and inequities in health care. “We have to acknowledge that there is racism in medicine. I think once we acknowledge that, then we can look at things in our practices that we need to change. We can think very broadly and look at things that perhaps disadvantage one population over another,” said Lori Pierce, MD, a radiation oncologist with the University of Michigan, Ann Arbor.

Dr. Pierce also emphasized the need to recruit more underrepresented groups to participate in clinical trials. For example, of six breast cancer clinical trials – for margetuximab (Margenza), sacituzumab govitecan (Trodelvy), tucatinib (Tukysa), trastuzumab deruxtecan (Enhertu), alpelisib (Piqray), and talazoparib (Talzenna), only a small percentage included Black, Asian, and Hispanic women. For trastuzumab deruxtecan, which is widely recognized as a best-in-class HER2-targeting antibody drug conjugate, 51% were White, 42% Asian, 6% Hispanic, and 3% Black. For sacituzumab govitecan, a blockbuster drug for triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer that disproportionately affects Black women, only 7% of women enrolled in clinical trials were Black. In clinical trials for margetuximab, approved to treat HER2-positive breast cancer, 80% of participants were White, 5% Black, 6% Asian, and 9% Hispanic.

There is a perception that minorities may be unwilling to participate in clinical trials, but that’s not true, according to Patty Spears, a research manager of the Patient Advocates for Research Council at the University of North Carolina. “We know that there are data that clearly show that patients will go on clinical trials at the same rate, whether they’re Black, White, Asian, or whatever. You have to be able to have them in your system and ask them to go on trial,” she said.

Another panelist told a personal anecdote to illustrate the point. Matthew Ellis, MD, PhD, recalled that he spent 13 years at Washington University in St. Louis, serving one of the more segregated cities in the United States. The city hospital closed, and Washington University and the Siteman Cancer Center signed a contract to treat the underserved population that was suddenly without a source of care. “Subsequent to that, we over-accrued relative to the population of African American patients. What that taught me is it’s nothing to do with the lack of willingness of African Americans to participate in clinical trials. Quite the opposite. It’s the question of access to clinical trials, access to great care, and not creating health care systems that segregate patients into places where they’re not getting access,” he said.

Breast cancer treatments have made great strides in recent years with significant reductions in overall mortality. However, the incidence of breast cancer has increased just slightly in recent years after a dip in the early 2000s.

“The good news is that mortality is decreasing, but it still remains high. We still have a long way to go to tackle this problem of breast cancer incidence as well as the number of deaths,” said Angela DeMichele, MD, co-leader of the breast cancer research program at the University of Pennsylvania’s Abramson Cancer Center. She participated in a session on obstacles in breast cancer treatment held in December at the San Antonio Breast Cancer Symposium. She joined other oncologists in outlining key challenges that need to be addressed to improve breast cancer diagnosis and treatment.

They highlighted six obstacles: The need for more prevention/early detection strategies; the underutilization of artificial intelligence; underuse of precision oncology such as targeted therapies; the need for innovation in clinical trials; a widening gap in cancer disparities; and the need to align incentives and funding for research collaboration, training, and retention.

Since 2012, the Food and Drug Administration has approved 20 new therapeutics to treat breast cancer. Nadia Harbeck, MD, PhD, director of the breast center at LMU University Hospital, Munich, said that the development of new therapies has in a way become a victim of its own success. Therapies and survival have improved, making it harder to compare novel therapies to the standard of care and prove a benefit. Treatment guidelines are changing so quickly that clinical trials are sometimes obsolete by the time they are published because of changes to the standard of care. That places a need on more real-world evidence that can be designed to be useful in the clinic, and AI can help here. “We need to convince regulators to act upon cleverly planned real world evidence analysis. You can randomize them, you can use registries, and you should also be able to change labels because of [new] data,” Dr. Harbeck said.

There are many risk factors that drive breast cancer, and it is very heterogeneous, said Christine Ambrosone, PhD, chair of the department of cancer prevention and control at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y. She called for identifying patients who are at risk for a poor prognosis, such as patients with hormone receptor–negative breast cancer, high-grade, and triple-negative breast cancer. Otherwise there is a risk of overtreatment of low-risk tumors, which could potentially be identified with new tools in precision oncology such as liquid biopsy tests, also known as multicancer early detection tests. These tests can detect cancers long before they become symptomatic. The first such test was launched this year and many more are in clinical trials.

Regina Barzilay, PhD, professor and expert in the use of artificial intelligence in health at the Massachusetts Institute of Technology, pointed out that machine learning is used in many fields, but hardly at all in breast cancer. It could be applied to data on biomarkers and other factors collected from retrospective analyses and clinical trials. She added that machine learning is often applied to biochemistry and single cell analysis of other tumor types, but rarely in breast cancer. “It is severely underutilized,” Dr. Barzilay said. One challenge is that researchers are not necessarily familiar with the techniques of machine learning and AI. Another issue is that breast cancer data are not easy to share and may not be readily available to AI researchers. “An investment in interchangeable data is crucially important,” she said.

Artificial intelligence could assist in identifying and modeling factors that contribute to cancer risk by teasing apart complicated relationships, such as the association between pregnancy, breastfeeding, and breast cancer risk. Pregnancy reduces the risk of hormone receptor–positive disease, but increases the risk of hormone receptor–negative disease.

Another key challenge is the underuse of “omics” technologies, which measure large scale patterns in biological characteristics such as gene variation or protein expression. That has roots in the history of breast cancer being considered as a separate entity from other solid tumors such as lung or pancreatic cancer. Fabrice André, MD, PhD, an oncologist with Gustave Roussy Cancer Center, France, emphasized that breast cancer shouldn’t be considered an entity when it’s metastatic. Instead, tumors should be defined by molecular characteristics they share. He anticipates a personalized medicine future where academic and industry groups collaborate to create an individualized therapy for patients based on genetic factors.
 

Access to therapies for all patients

Novel and effective therapies can make a difference only if patients have access to them, and a key obstacle to improving breast cancer care is racism and inequities in health care. “We have to acknowledge that there is racism in medicine. I think once we acknowledge that, then we can look at things in our practices that we need to change. We can think very broadly and look at things that perhaps disadvantage one population over another,” said Lori Pierce, MD, a radiation oncologist with the University of Michigan, Ann Arbor.

Dr. Pierce also emphasized the need to recruit more underrepresented groups to participate in clinical trials. For example, of six breast cancer clinical trials – for margetuximab (Margenza), sacituzumab govitecan (Trodelvy), tucatinib (Tukysa), trastuzumab deruxtecan (Enhertu), alpelisib (Piqray), and talazoparib (Talzenna), only a small percentage included Black, Asian, and Hispanic women. For trastuzumab deruxtecan, which is widely recognized as a best-in-class HER2-targeting antibody drug conjugate, 51% were White, 42% Asian, 6% Hispanic, and 3% Black. For sacituzumab govitecan, a blockbuster drug for triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer that disproportionately affects Black women, only 7% of women enrolled in clinical trials were Black. In clinical trials for margetuximab, approved to treat HER2-positive breast cancer, 80% of participants were White, 5% Black, 6% Asian, and 9% Hispanic.

There is a perception that minorities may be unwilling to participate in clinical trials, but that’s not true, according to Patty Spears, a research manager of the Patient Advocates for Research Council at the University of North Carolina. “We know that there are data that clearly show that patients will go on clinical trials at the same rate, whether they’re Black, White, Asian, or whatever. You have to be able to have them in your system and ask them to go on trial,” she said.

Another panelist told a personal anecdote to illustrate the point. Matthew Ellis, MD, PhD, recalled that he spent 13 years at Washington University in St. Louis, serving one of the more segregated cities in the United States. The city hospital closed, and Washington University and the Siteman Cancer Center signed a contract to treat the underserved population that was suddenly without a source of care. “Subsequent to that, we over-accrued relative to the population of African American patients. What that taught me is it’s nothing to do with the lack of willingness of African Americans to participate in clinical trials. Quite the opposite. It’s the question of access to clinical trials, access to great care, and not creating health care systems that segregate patients into places where they’re not getting access,” he said.

Dr Peter Martin, from Weill Cornell Medicine in New York, NY, highlights breakthroughs and developments in mantle cell lymphoma presented at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition. 

Dr Martin begins with the top-ranked abstract from the meeting, a European trial that looked at ibrutinib as a substitute for autologous stem cell transplantation (ASCT) in younger patients. The results suggest that the era of upfront ASCT may now be over. 

Next, he reports on a trial that investigated the addition of the second-generation BTK inhibitor acalabrutinib to lenalidomide and rituximab. The combination provided excellent clinical responses, indicating that mantle cell lymphoma patients may soon be able to avoid chemotherapy altogether. 

The next trial selected by Dr Martin examined whether the addition of lenalidomide to consolidation rituximab after first-line bendamustine-rituximab would improve survival outcomes. The study reported no additional benefit, at the cost of increased adverse events. 

Dr Martin closes by discussing two trials in the relapsed/refractory setting, one a phase 1 trial of the bispecific antibody glofitamab, the other a phase 1b-2 trial of venetoclax with lenalidomide and rituximab. Both showed encouraging results that point to potential future treatment strategies. 

--

Associate Professor of Medicine, Weill Cornell Medicine, New York, NY 

Peter Martin, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; ADCT; BeiGene; Bristol Myers Squibb; Epizyme; Genentech; Gilead; Janssen; Takeda 

Dr Peter Martin, from Weill Cornell Medicine in New York, NY, highlights breakthroughs and developments in mantle cell lymphoma presented at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition. 

Dr Martin begins with the top-ranked abstract from the meeting, a European trial that looked at ibrutinib as a substitute for autologous stem cell transplantation (ASCT) in younger patients. The results suggest that the era of upfront ASCT may now be over. 

Next, he reports on a trial that investigated the addition of the second-generation BTK inhibitor acalabrutinib to lenalidomide and rituximab. The combination provided excellent clinical responses, indicating that mantle cell lymphoma patients may soon be able to avoid chemotherapy altogether. 

The next trial selected by Dr Martin examined whether the addition of lenalidomide to consolidation rituximab after first-line bendamustine-rituximab would improve survival outcomes. The study reported no additional benefit, at the cost of increased adverse events. 

Dr Martin closes by discussing two trials in the relapsed/refractory setting, one a phase 1 trial of the bispecific antibody glofitamab, the other a phase 1b-2 trial of venetoclax with lenalidomide and rituximab. Both showed encouraging results that point to potential future treatment strategies. 

--

Associate Professor of Medicine, Weill Cornell Medicine, New York, NY 

Peter Martin, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; ADCT; BeiGene; Bristol Myers Squibb; Epizyme; Genentech; Gilead; Janssen; Takeda 

Dr Peter Martin, from Weill Cornell Medicine in New York, NY, highlights breakthroughs and developments in mantle cell lymphoma presented at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition. 

Dr Martin begins with the top-ranked abstract from the meeting, a European trial that looked at ibrutinib as a substitute for autologous stem cell transplantation (ASCT) in younger patients. The results suggest that the era of upfront ASCT may now be over. 

Next, he reports on a trial that investigated the addition of the second-generation BTK inhibitor acalabrutinib to lenalidomide and rituximab. The combination provided excellent clinical responses, indicating that mantle cell lymphoma patients may soon be able to avoid chemotherapy altogether. 

The next trial selected by Dr Martin examined whether the addition of lenalidomide to consolidation rituximab after first-line bendamustine-rituximab would improve survival outcomes. The study reported no additional benefit, at the cost of increased adverse events. 

Dr Martin closes by discussing two trials in the relapsed/refractory setting, one a phase 1 trial of the bispecific antibody glofitamab, the other a phase 1b-2 trial of venetoclax with lenalidomide and rituximab. Both showed encouraging results that point to potential future treatment strategies. 

--

Associate Professor of Medicine, Weill Cornell Medicine, New York, NY 

Peter Martin, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; ADCT; BeiGene; Bristol Myers Squibb; Epizyme; Genentech; Gilead; Janssen; Takeda 

As a toddler undergoing treatment at McMaster Children’s Hospital in Hamilton, Ont., Caroline Diorio, MD, couldn’t grasp what the nice doctors scurrying in and out of her room were doing. She just knew they were taking care of her.

Dr. Diorio had pediatric immune thrombocytopenia (ITP), a type of platelet disorder in which the immune system attacks blood platelets for usually unknown reasons.

“I remember very much how worried my parents were,” recalled Dr. Diorio, now a hematologist-oncologist at Children’s Hospital of Philadelphia. “And I remember how the tone of the doctor’s voice and the way the doctors communicated provided so much reassurance to my parents.”

Dr. Diorio’s ITP resolved within a few years, but her experience left a lasting impression.

“From that moment on, I don’t remember a time that I didn’t want to be a doctor,” she said. “I had these really formative experiences with doctors who were so lovely, and I thought, ‘I want to do that.’ ”

Though she considered other specialties in medical school at the University of Toronto, Dr. Diorio kept feeling drawn back to pediatric oncology and hematology.

“I have always loved the commitment that parents have to their kids and the team approach that exists,” she said. “Hematology/oncology allowed me to take care of really sick kids but also have this long-term relationship with them and their parents, which I really value and love.”

Dr. Diorio even completed her residency at McMaster alongside one of the same physicians who had cared for her as a child, Ronald Duncan Barr, MD. “It sort of all came full circle,” she said.

Today, Dr. Diorio draws inspiration from memories of her childhood experience. “I try to recreate that and provide as much kindness and compassion as I can for patients and their families, to help when people are in this incredibly vulnerable situation,” she said.

But she takes that even further by researching new therapies for patients who have run out of options, particularly those with T-cell acute lymphoblastic leukemia (T-ALL).

For B-cell ALL and several other blood cancers, an effective option is CAR T-cell therapy, in which physicians collect T-cells from the patient, re-engineer the T cells in the lab so they recognize the proteins expressed on the surface of cancerous cells – called blasts – and then introduce the modified T-cells back into the patient. Once infused, the re-engineered T-cells attack the blasts with the tell-tale proteins.

But with T-ALL, T-cells themselves are infected with cancer, so autologous CAR T-cell therapy is not currently an option, and no allogeneic CAR T-cell therapies have been approved. Dr. Diorio is part of a cutting-edge research team led by David T. Teachey, MD, striving for breakthroughs. “She’s a brilliant clinician, extremely smart and hard-working, exceptional work ethic, great interaction with patients and families with a great bedside manner,” Dr. Teachey said of Dr. Diorio. “She’s just a superstar all around.”

Dr. Teachey first piqued Dr. Diorio’s interest in researching innovative T-ALL therapies when she arrived at CHOP as a hematology/oncology fellow in 2018 and pursued a master of science degree in translational research under his tutelage at the University of Pennsylvania. Then, for a time, the COVID-19 pandemic shut down most research.

“Caroline pivoted and was at the front line, collecting samples and helping with research on SARS-CoV-2 very early in the pandemic,” Dr. Teachey said. “She was able to then pivot back, taking the skills she learned from that work in the pandemic and applying it to what she was doing in the CAR T-cell space and T-ALL.”

Extraordinary gains in pediatric cancer over the past several decades mean that more than 80% of children diagnosed with cancer today will become long-term survivors. “The 20% of the time that we don’t get the result we want is obviously devastating,” Dr. Diorio said. “However, that’s incredibly motivating to try to make better treatments.”

Her current focus is finding a way to use CAR T-cell therapy in children with T-ALL. About 85% of children with T-ALL do well with standard first-line treatments of chemotherapy, but the 15% who relapse or have chemo-refractory disease have a far lower survival rate – less than 30%, Dr. Diorio said.

The problem with autologous CAR T-cell therapy in T-ALL is twofold: It’s difficult to sort out healthy T cells from the cancerous T cells, and the target current re-engineered T-cells go after is on healthy cells, too.

“What happens is a problem called fratricide – basically the CAR T-cells are killing their brothers,” she said. So Dr. Diorio and her colleagues are trying to modify CAR T-cell strategies to target different markers. One target they’re investigating is CD7, but using CRISPR to gene-edit out CD7 from healthy cells requires making two cuts in the DNA.

“Any time you break DNA, you have to repair it, and any time you repair it, there’s a chance of making a mistake,” Dr. Diorio said. So she used a different technique, cytosine-based editing, which requires only one cut. “You put in what you want, and it’s much more precise and less error-prone.” Cytosine-based editing also preserves T cells’ vitality; too many cuts impair T-cell growth, but that doesn’t happen with cytosine-based editing. In August of 2022, Dr. Diorio published a study demonstrating this technique while the team has continued looking for other targets that show up on cancer cells but not on healthy T-cells.

“I’m not invested in one particular strategy,” Dr. Diorio said. “I’m invested in finding a strategy that works for the maximum number of patients.”

That pragmatic approach may be why Dr. Teachey describes her as an out-of-the-box thinker.

“She brings novel ideas to the table, and not everybody who’s a physician-scientist has that ability to really think about taking things in the bench to the bedside and then back again,” Dr. Teachey said. “It’s knowing what questions are important to ask for our patients and how to study those and the research base, so that you can improve treatments for kids with leukemia.”

Their research looks promising so far. Clinical trials are in development for the CD7-targeted CAR T, and they’re collaborating with others on clinical trials for CAR-T targeting another protein, CD38. In the midst of it all, Dr. Diorio remains focused on her patients.

“It’s really a privilege to see the incredible grace people have in these very difficult circumstances,” Dr. Diorio said. “I find it really motivating to try to make things easier for people, and I try to spend every day looking for better treatments so people don’t have to go through that.”

Dr. Diorio has no disclosures. Dr. Teachey has served on the advisory boards of BEAM, Jazz, Janssen, and Sobi and has received research funding from BEAM, Jazz, Servier, and Neoimmune Tech. He has multiple patents pending on CAR-T therapy.

As a toddler undergoing treatment at McMaster Children’s Hospital in Hamilton, Ont., Caroline Diorio, MD, couldn’t grasp what the nice doctors scurrying in and out of her room were doing. She just knew they were taking care of her.

Dr. Diorio had pediatric immune thrombocytopenia (ITP), a type of platelet disorder in which the immune system attacks blood platelets for usually unknown reasons.

“I remember very much how worried my parents were,” recalled Dr. Diorio, now a hematologist-oncologist at Children’s Hospital of Philadelphia. “And I remember how the tone of the doctor’s voice and the way the doctors communicated provided so much reassurance to my parents.”

Dr. Diorio’s ITP resolved within a few years, but her experience left a lasting impression.

“From that moment on, I don’t remember a time that I didn’t want to be a doctor,” she said. “I had these really formative experiences with doctors who were so lovely, and I thought, ‘I want to do that.’ ”

Though she considered other specialties in medical school at the University of Toronto, Dr. Diorio kept feeling drawn back to pediatric oncology and hematology.

“I have always loved the commitment that parents have to their kids and the team approach that exists,” she said. “Hematology/oncology allowed me to take care of really sick kids but also have this long-term relationship with them and their parents, which I really value and love.”

Dr. Diorio even completed her residency at McMaster alongside one of the same physicians who had cared for her as a child, Ronald Duncan Barr, MD. “It sort of all came full circle,” she said.

Today, Dr. Diorio draws inspiration from memories of her childhood experience. “I try to recreate that and provide as much kindness and compassion as I can for patients and their families, to help when people are in this incredibly vulnerable situation,” she said.

But she takes that even further by researching new therapies for patients who have run out of options, particularly those with T-cell acute lymphoblastic leukemia (T-ALL).

For B-cell ALL and several other blood cancers, an effective option is CAR T-cell therapy, in which physicians collect T-cells from the patient, re-engineer the T cells in the lab so they recognize the proteins expressed on the surface of cancerous cells – called blasts – and then introduce the modified T-cells back into the patient. Once infused, the re-engineered T-cells attack the blasts with the tell-tale proteins.

But with T-ALL, T-cells themselves are infected with cancer, so autologous CAR T-cell therapy is not currently an option, and no allogeneic CAR T-cell therapies have been approved. Dr. Diorio is part of a cutting-edge research team led by David T. Teachey, MD, striving for breakthroughs. “She’s a brilliant clinician, extremely smart and hard-working, exceptional work ethic, great interaction with patients and families with a great bedside manner,” Dr. Teachey said of Dr. Diorio. “She’s just a superstar all around.”

Dr. Teachey first piqued Dr. Diorio’s interest in researching innovative T-ALL therapies when she arrived at CHOP as a hematology/oncology fellow in 2018 and pursued a master of science degree in translational research under his tutelage at the University of Pennsylvania. Then, for a time, the COVID-19 pandemic shut down most research.

“Caroline pivoted and was at the front line, collecting samples and helping with research on SARS-CoV-2 very early in the pandemic,” Dr. Teachey said. “She was able to then pivot back, taking the skills she learned from that work in the pandemic and applying it to what she was doing in the CAR T-cell space and T-ALL.”

Extraordinary gains in pediatric cancer over the past several decades mean that more than 80% of children diagnosed with cancer today will become long-term survivors. “The 20% of the time that we don’t get the result we want is obviously devastating,” Dr. Diorio said. “However, that’s incredibly motivating to try to make better treatments.”

Her current focus is finding a way to use CAR T-cell therapy in children with T-ALL. About 85% of children with T-ALL do well with standard first-line treatments of chemotherapy, but the 15% who relapse or have chemo-refractory disease have a far lower survival rate – less than 30%, Dr. Diorio said.

The problem with autologous CAR T-cell therapy in T-ALL is twofold: It’s difficult to sort out healthy T cells from the cancerous T cells, and the target current re-engineered T-cells go after is on healthy cells, too.

“What happens is a problem called fratricide – basically the CAR T-cells are killing their brothers,” she said. So Dr. Diorio and her colleagues are trying to modify CAR T-cell strategies to target different markers. One target they’re investigating is CD7, but using CRISPR to gene-edit out CD7 from healthy cells requires making two cuts in the DNA.

“Any time you break DNA, you have to repair it, and any time you repair it, there’s a chance of making a mistake,” Dr. Diorio said. So she used a different technique, cytosine-based editing, which requires only one cut. “You put in what you want, and it’s much more precise and less error-prone.” Cytosine-based editing also preserves T cells’ vitality; too many cuts impair T-cell growth, but that doesn’t happen with cytosine-based editing. In August of 2022, Dr. Diorio published a study demonstrating this technique while the team has continued looking for other targets that show up on cancer cells but not on healthy T-cells.

“I’m not invested in one particular strategy,” Dr. Diorio said. “I’m invested in finding a strategy that works for the maximum number of patients.”

That pragmatic approach may be why Dr. Teachey describes her as an out-of-the-box thinker.

“She brings novel ideas to the table, and not everybody who’s a physician-scientist has that ability to really think about taking things in the bench to the bedside and then back again,” Dr. Teachey said. “It’s knowing what questions are important to ask for our patients and how to study those and the research base, so that you can improve treatments for kids with leukemia.”

Their research looks promising so far. Clinical trials are in development for the CD7-targeted CAR T, and they’re collaborating with others on clinical trials for CAR-T targeting another protein, CD38. In the midst of it all, Dr. Diorio remains focused on her patients.

“It’s really a privilege to see the incredible grace people have in these very difficult circumstances,” Dr. Diorio said. “I find it really motivating to try to make things easier for people, and I try to spend every day looking for better treatments so people don’t have to go through that.”

Dr. Diorio has no disclosures. Dr. Teachey has served on the advisory boards of BEAM, Jazz, Janssen, and Sobi and has received research funding from BEAM, Jazz, Servier, and Neoimmune Tech. He has multiple patents pending on CAR-T therapy.

As a toddler undergoing treatment at McMaster Children’s Hospital in Hamilton, Ont., Caroline Diorio, MD, couldn’t grasp what the nice doctors scurrying in and out of her room were doing. She just knew they were taking care of her.

Dr. Diorio had pediatric immune thrombocytopenia (ITP), a type of platelet disorder in which the immune system attacks blood platelets for usually unknown reasons.

“I remember very much how worried my parents were,” recalled Dr. Diorio, now a hematologist-oncologist at Children’s Hospital of Philadelphia. “And I remember how the tone of the doctor’s voice and the way the doctors communicated provided so much reassurance to my parents.”

Dr. Diorio’s ITP resolved within a few years, but her experience left a lasting impression.

“From that moment on, I don’t remember a time that I didn’t want to be a doctor,” she said. “I had these really formative experiences with doctors who were so lovely, and I thought, ‘I want to do that.’ ”

Though she considered other specialties in medical school at the University of Toronto, Dr. Diorio kept feeling drawn back to pediatric oncology and hematology.

“I have always loved the commitment that parents have to their kids and the team approach that exists,” she said. “Hematology/oncology allowed me to take care of really sick kids but also have this long-term relationship with them and their parents, which I really value and love.”

Dr. Diorio even completed her residency at McMaster alongside one of the same physicians who had cared for her as a child, Ronald Duncan Barr, MD. “It sort of all came full circle,” she said.

Today, Dr. Diorio draws inspiration from memories of her childhood experience. “I try to recreate that and provide as much kindness and compassion as I can for patients and their families, to help when people are in this incredibly vulnerable situation,” she said.

But she takes that even further by researching new therapies for patients who have run out of options, particularly those with T-cell acute lymphoblastic leukemia (T-ALL).

For B-cell ALL and several other blood cancers, an effective option is CAR T-cell therapy, in which physicians collect T-cells from the patient, re-engineer the T cells in the lab so they recognize the proteins expressed on the surface of cancerous cells – called blasts – and then introduce the modified T-cells back into the patient. Once infused, the re-engineered T-cells attack the blasts with the tell-tale proteins.

But with T-ALL, T-cells themselves are infected with cancer, so autologous CAR T-cell therapy is not currently an option, and no allogeneic CAR T-cell therapies have been approved. Dr. Diorio is part of a cutting-edge research team led by David T. Teachey, MD, striving for breakthroughs. “She’s a brilliant clinician, extremely smart and hard-working, exceptional work ethic, great interaction with patients and families with a great bedside manner,” Dr. Teachey said of Dr. Diorio. “She’s just a superstar all around.”

Dr. Teachey first piqued Dr. Diorio’s interest in researching innovative T-ALL therapies when she arrived at CHOP as a hematology/oncology fellow in 2018 and pursued a master of science degree in translational research under his tutelage at the University of Pennsylvania. Then, for a time, the COVID-19 pandemic shut down most research.

“Caroline pivoted and was at the front line, collecting samples and helping with research on SARS-CoV-2 very early in the pandemic,” Dr. Teachey said. “She was able to then pivot back, taking the skills she learned from that work in the pandemic and applying it to what she was doing in the CAR T-cell space and T-ALL.”

Extraordinary gains in pediatric cancer over the past several decades mean that more than 80% of children diagnosed with cancer today will become long-term survivors. “The 20% of the time that we don’t get the result we want is obviously devastating,” Dr. Diorio said. “However, that’s incredibly motivating to try to make better treatments.”

Her current focus is finding a way to use CAR T-cell therapy in children with T-ALL. About 85% of children with T-ALL do well with standard first-line treatments of chemotherapy, but the 15% who relapse or have chemo-refractory disease have a far lower survival rate – less than 30%, Dr. Diorio said.

The problem with autologous CAR T-cell therapy in T-ALL is twofold: It’s difficult to sort out healthy T cells from the cancerous T cells, and the target current re-engineered T-cells go after is on healthy cells, too.

“What happens is a problem called fratricide – basically the CAR T-cells are killing their brothers,” she said. So Dr. Diorio and her colleagues are trying to modify CAR T-cell strategies to target different markers. One target they’re investigating is CD7, but using CRISPR to gene-edit out CD7 from healthy cells requires making two cuts in the DNA.

“Any time you break DNA, you have to repair it, and any time you repair it, there’s a chance of making a mistake,” Dr. Diorio said. So she used a different technique, cytosine-based editing, which requires only one cut. “You put in what you want, and it’s much more precise and less error-prone.” Cytosine-based editing also preserves T cells’ vitality; too many cuts impair T-cell growth, but that doesn’t happen with cytosine-based editing. In August of 2022, Dr. Diorio published a study demonstrating this technique while the team has continued looking for other targets that show up on cancer cells but not on healthy T-cells.

“I’m not invested in one particular strategy,” Dr. Diorio said. “I’m invested in finding a strategy that works for the maximum number of patients.”

That pragmatic approach may be why Dr. Teachey describes her as an out-of-the-box thinker.

“She brings novel ideas to the table, and not everybody who’s a physician-scientist has that ability to really think about taking things in the bench to the bedside and then back again,” Dr. Teachey said. “It’s knowing what questions are important to ask for our patients and how to study those and the research base, so that you can improve treatments for kids with leukemia.”

Their research looks promising so far. Clinical trials are in development for the CD7-targeted CAR T, and they’re collaborating with others on clinical trials for CAR-T targeting another protein, CD38. In the midst of it all, Dr. Diorio remains focused on her patients.

“It’s really a privilege to see the incredible grace people have in these very difficult circumstances,” Dr. Diorio said. “I find it really motivating to try to make things easier for people, and I try to spend every day looking for better treatments so people don’t have to go through that.”

Dr. Diorio has no disclosures. Dr. Teachey has served on the advisory boards of BEAM, Jazz, Janssen, and Sobi and has received research funding from BEAM, Jazz, Servier, and Neoimmune Tech. He has multiple patents pending on CAR-T therapy.

Test

Test

Test

The U.S. Food and Drug Administration has approved mosunetuzumab-axgb (Lunsumio) for use in patients with relapsed or refractory follicular lymphoma who have received at least two previous systemic therapies.

This product is a first-in-class bispecific antibody that is designed to target CD20 on the surface of B cells and CD3 on the surface of T cells. This dual targeting activates and redirects a patient’s existing T cells to engage and eliminate target B cells by releasing cytotoxic proteins into the B cells, according to the manufacturer, Genentech.

Mosunetuzumab-axgb is administered as an intravenous infusion for a fixed duration, which allows for time off therapy, and can be infused in an outpatient setting, the company noted.

The drug was granted an accelerated approval on the basis of response rate data from the phase 2 GO29781 trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial, the company noted.

The GO29781 study was carried out in individuals with pretreated follicular lymphoma, including those who were at high risk for disease progression or whose disease was refractory to prior therapies.

A complete response was achieved in 60% of patients (54 of 90).

An objective response rate (a combination of complete and partial responses) was seen in 80% of patients who received the drug, with a majority maintaining responses for at least 18 months.

The median duration of response among those who responded was 22.8 months.

Safety data come from 218 patients with hematologic cancers who received mosunetuzumab-axgb at the recommended dose. The most common adverse event was cytokine release syndrome (39%), which can be severe and life-threatening. The median duration of cytokine release syndrome events was 3 days (range, 1-29 days). Other common adverse events (≥ 20%) included fatigue, rash, pyrexia, and headache.

“This approval is a significant milestone for people with relapsed or refractory follicular lymphoma, who have had limited treatment options until now,” said Elizabeth Budde, MD, PhD, from the City of Hope, Los Angeles, division of lymphoma, and clinical trial investigator.

Dr. Budde presented data on mosunetuzumab-axgb at the 2021 annual meeting of the American Society of Hematology, as reported by this news organization.

She noted that the 60% complete response rate seen with this new drug contrasts with the 14% that has been seen for historical controls.

“We have seen deep and durable responses in heavily pretreated, high-risk relapsed/refractory follicular lymphoma patients with fixed-duration treatment. We also observed a very favorable tolerability profile, with most cytokine release syndrome confined to cycle 1 and low grade, and treatment administration is without mandatory hospitalization,” she commented at the time.

A lymphoma specialist who was not involved in the study told this news organization at the time that he was favorably impressed by the findings.

“To me, the single-agent data looks really outstanding, with a response rate of 80%, a complete response rate of 60%, and a median duration of response of 23 months, and really very acceptable rates of cytokine release syndrome,” commented Brad S. Kahl, MD, from the Siteman Cancer Center and Washington University in St. Louis.

“I think as a single agent – if it does get approval – it will be a really valuable addition to the armamentarium in follicular lymphoma,” he added.

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

The U.S. Food and Drug Administration has approved mosunetuzumab-axgb (Lunsumio) for use in patients with relapsed or refractory follicular lymphoma who have received at least two previous systemic therapies.

This product is a first-in-class bispecific antibody that is designed to target CD20 on the surface of B cells and CD3 on the surface of T cells. This dual targeting activates and redirects a patient’s existing T cells to engage and eliminate target B cells by releasing cytotoxic proteins into the B cells, according to the manufacturer, Genentech.

Mosunetuzumab-axgb is administered as an intravenous infusion for a fixed duration, which allows for time off therapy, and can be infused in an outpatient setting, the company noted.

The drug was granted an accelerated approval on the basis of response rate data from the phase 2 GO29781 trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial, the company noted.

The GO29781 study was carried out in individuals with pretreated follicular lymphoma, including those who were at high risk for disease progression or whose disease was refractory to prior therapies.

A complete response was achieved in 60% of patients (54 of 90).

An objective response rate (a combination of complete and partial responses) was seen in 80% of patients who received the drug, with a majority maintaining responses for at least 18 months.

The median duration of response among those who responded was 22.8 months.

Safety data come from 218 patients with hematologic cancers who received mosunetuzumab-axgb at the recommended dose. The most common adverse event was cytokine release syndrome (39%), which can be severe and life-threatening. The median duration of cytokine release syndrome events was 3 days (range, 1-29 days). Other common adverse events (≥ 20%) included fatigue, rash, pyrexia, and headache.

“This approval is a significant milestone for people with relapsed or refractory follicular lymphoma, who have had limited treatment options until now,” said Elizabeth Budde, MD, PhD, from the City of Hope, Los Angeles, division of lymphoma, and clinical trial investigator.

Dr. Budde presented data on mosunetuzumab-axgb at the 2021 annual meeting of the American Society of Hematology, as reported by this news organization.

She noted that the 60% complete response rate seen with this new drug contrasts with the 14% that has been seen for historical controls.

“We have seen deep and durable responses in heavily pretreated, high-risk relapsed/refractory follicular lymphoma patients with fixed-duration treatment. We also observed a very favorable tolerability profile, with most cytokine release syndrome confined to cycle 1 and low grade, and treatment administration is without mandatory hospitalization,” she commented at the time.

A lymphoma specialist who was not involved in the study told this news organization at the time that he was favorably impressed by the findings.

“To me, the single-agent data looks really outstanding, with a response rate of 80%, a complete response rate of 60%, and a median duration of response of 23 months, and really very acceptable rates of cytokine release syndrome,” commented Brad S. Kahl, MD, from the Siteman Cancer Center and Washington University in St. Louis.

“I think as a single agent – if it does get approval – it will be a really valuable addition to the armamentarium in follicular lymphoma,” he added.

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

The U.S. Food and Drug Administration has approved mosunetuzumab-axgb (Lunsumio) for use in patients with relapsed or refractory follicular lymphoma who have received at least two previous systemic therapies.

This product is a first-in-class bispecific antibody that is designed to target CD20 on the surface of B cells and CD3 on the surface of T cells. This dual targeting activates and redirects a patient’s existing T cells to engage and eliminate target B cells by releasing cytotoxic proteins into the B cells, according to the manufacturer, Genentech.

Mosunetuzumab-axgb is administered as an intravenous infusion for a fixed duration, which allows for time off therapy, and can be infused in an outpatient setting, the company noted.

The drug was granted an accelerated approval on the basis of response rate data from the phase 2 GO29781 trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial, the company noted.

The GO29781 study was carried out in individuals with pretreated follicular lymphoma, including those who were at high risk for disease progression or whose disease was refractory to prior therapies.

A complete response was achieved in 60% of patients (54 of 90).

An objective response rate (a combination of complete and partial responses) was seen in 80% of patients who received the drug, with a majority maintaining responses for at least 18 months.

The median duration of response among those who responded was 22.8 months.

Safety data come from 218 patients with hematologic cancers who received mosunetuzumab-axgb at the recommended dose. The most common adverse event was cytokine release syndrome (39%), which can be severe and life-threatening. The median duration of cytokine release syndrome events was 3 days (range, 1-29 days). Other common adverse events (≥ 20%) included fatigue, rash, pyrexia, and headache.

“This approval is a significant milestone for people with relapsed or refractory follicular lymphoma, who have had limited treatment options until now,” said Elizabeth Budde, MD, PhD, from the City of Hope, Los Angeles, division of lymphoma, and clinical trial investigator.

Dr. Budde presented data on mosunetuzumab-axgb at the 2021 annual meeting of the American Society of Hematology, as reported by this news organization.

She noted that the 60% complete response rate seen with this new drug contrasts with the 14% that has been seen for historical controls.

“We have seen deep and durable responses in heavily pretreated, high-risk relapsed/refractory follicular lymphoma patients with fixed-duration treatment. We also observed a very favorable tolerability profile, with most cytokine release syndrome confined to cycle 1 and low grade, and treatment administration is without mandatory hospitalization,” she commented at the time.

A lymphoma specialist who was not involved in the study told this news organization at the time that he was favorably impressed by the findings.

“To me, the single-agent data looks really outstanding, with a response rate of 80%, a complete response rate of 60%, and a median duration of response of 23 months, and really very acceptable rates of cytokine release syndrome,” commented Brad S. Kahl, MD, from the Siteman Cancer Center and Washington University in St. Louis.

“I think as a single agent – if it does get approval – it will be a really valuable addition to the armamentarium in follicular lymphoma,” he added.

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

“It is one of life’s most self-evident truths that everything fades, that we fear the fading, and that we must live, nonetheless, in the face of the fear.” – Irvin D. Yalom, MD, Existential Psychotherapy, 1980

The email was titled simply, “A sorrowful note,” and I knew that someone had died. I held my breath and read as Dr. Jimmy Potash informed our entire department that Dr. Cait McFarland died in a car accident on December 7 while driving to work at West Cecil Health Center, Conowingo, Md., where she was director of psychiatry.

Sadness swelled as I remembered the outspoken resident who was interested in LGBTQ issues. Cait graduated from the Johns Hopkins residency program in 2020, she had recently married a social worker in the department, and the plan was for her to return to Hopkins full-time in July 2023 to be director of a clinic focused on mental health for people who are transgendered.

Sudden deaths are tragic and jarring and they call to the surface our losses from the past. These deaths don’t stand alone – I found myself thinking of my editor at Medscape, Dr. Bret Stetka, who died unexpectedly in August 2022, and then of Dr. Lidia Palcan Wenz, a psychiatrist I trained with, who died in a motor vehicle accident in 2004. Lidia’s husband also died in the accident, while their two young children in the back seat survived – this tragedy haunted me for some time. None of these people was close to me, but I am no stranger to the impact of unexpected death: My parents and brother all died from cardiac events, and any sudden death is a reminder of those losses.

Julia Riddle, MD, trained with Cait McFarland and was her close friend for years. “I don’t have a belief in ‘the afterlife’ but do like to think of the people that I have lost together in my memory – as if they are all suddenly in a new room together. And, with each loss, all the other occupants of that room come freshly to life again,” Dr. Riddle said.

Death is our shared destination in life, but sudden and unexpected deaths carry their own weight. There is no chance to tie up loose ends, to repair riffs, to say goodbye. Nothing is put in order, and the life that was to be lived goes on for some time as bills arrive, social and work events go unattended, vacations are canceled, and there is the awkward moment of running into someone who didn’t know your loved one has died.

Roger Lewin, MD, is a psychiatrist and writer in Towson, Md. He has both personal and professional experience with sudden death. “There is no way to prepare beforehand, so we have to get ready for what has already happened, and that is hard,” he said. “We invent a life for ourselves and others that extends into the future, and that gets interrupted.”

Most people become ill and die on a vaguely predictable schedule. There may be a chance to plan, to know and honor the wishes of the individual, and often there is the opportunity for loved ones to begin the grieving process gradually as death approaches. For those who are elderly, there may be a sense that this is the natural order of things – which may or may not temper the intensity of the grief for those who remain. If the person has suffered, the end may come with relief.

Still, I sometimes find myself surprised at the length and intensity of anguish that some people experience after losing a loved one who has lived a long and full life, who declined and suffered, but whose absence remains a gaping wound that takes years to form a scar.

Sudden death is not rare; accidents, homicide, and suicide are the top killers among young people, and cardiovascular deaths are number one among those who are older. Natural disasters and terrorist attacks can cause catastrophic numbers of sudden deaths and leave survivors to grieve not only the dead, but the loss of all that was familiar to them.

Psychiatry has been a bit lost as to how we approach grief. We often hear patients talk about anxiety surrounding death and illness, be it a fear of death or a longing for it. These fears can seem irrational – I am reminded of a patient who was afraid to eat romaine because of news reports that it was responsible for food poisoning in other states, but not Maryland, where the person lived. I found it odd that he worried about eating lettuce, but not about smoking two packs of cigarettes a day.

But our fears are like that – they move to what the media sensationalizes, or to what may be remote, because otherwise no one would get in a car or clear their walkway of snow. Life is most easily lived with a bit of denial: We shut out the reality that we can be here one moment, overscheduled and overwhelmed, with deadlines, mortgage payments, and summer vacation plans, oblivious to the fact that life may end at any moment. The early months of COVID-19 felt like a global game of Russian roulette, with each venture out a pull of the trigger and everyone’s defenses stripped bare.

While death belongs to us all, we relegate it to the disciplines of religion, philosophy, the arts, and psychology. Religion offers answers – whether a heaven, a hell, or continual reincarnation until the individual attains enlightenment, there is a destination. Perhaps it will be pleasant, perhaps not, and for some there is the hope that one gets to be the driver by having the right beliefs or doing good deeds, while others are comforted by the hope of being reunited with loved ones.

“The suddenness endures and the shock lasts – it’s like a meteor that creates a crater and we revisit it in different ways from different angles,” Dr. Lewin said. “It may leap on us unexpectedly, often many years later.”

Patients talk about death, and when their fears seem unrealistic we may long to reassure them, yet there is no reassurance and psychiatry grasps for how to help. Psychiatry has looked to draw lines for when normal grief crosses to abnormal. Is it an adjustment disorder, complicated grief, “prolonged” grief, pathology in need of medication and medicalization, or something one experiences individually, sometimes for a very long time even with treatment?

One justification for pathologizing “prolonged” reactions includes the fact that insurers will pay for treatment only if there is a diagnosis code, and shouldn’t people in distress be entitled to psychotherapy or medication? Yet there is something offensive about telling someone that they are mentally ill if they don’t grieve along a prescribed timeline, as much as there is about denying them the possible benefits of therapy or medication if they seek it, but are suffering in all the “right” ways. Psychiatry’s approach to death is inelegant at best.

In his poignant podcast series, All There Is, Anderson Cooper is tasked with sorting through his mother’s apartment after her death at age 95. In the course of packing up her belongings, he brings on other guests to talk about their emotional reactions to death. Mr. Cooper’s mother, Gloria Vanderbilt, died at an advanced age, but his father died after a brief cardiac illness when Mr. Cooper was a child, and his brother died by suicide when he was 21. He uses these experiences as a springboard to examine childhood losses, the aftermath of suicide, and the loneliness of grief.

“Loss and grief is this universal experience that we will all go through multiple times in our lives,” Mr. Cooper says, “And yet it leaves us feeling so alone and so separated from other people. At least it does me and has my entire life.”

When we talk about grief and loss, we talk about “getting over it,” or “moving on.” But loss doesn’t work that way – time usually eases the pain, leaving scars that are part of the road map for who we are on the journey that defines us.

Sudden death is hard, and the unexpected death of a young person is tragic. For Cait McFarland, there are the decades she won’t get to experience. For her family and friends, it may be excruciating, and for all the patients who have lost a psychiatrist, may time bring healing and peace.

The Dr. Caitlin McFarland Educational Fund for LGBTQI+ Mental Health is being established, and donations are being accepted at https://www.gofundme.com/f/in-memory-of-cait-mcfarland.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships.

“It is one of life’s most self-evident truths that everything fades, that we fear the fading, and that we must live, nonetheless, in the face of the fear.” – Irvin D. Yalom, MD, Existential Psychotherapy, 1980

The email was titled simply, “A sorrowful note,” and I knew that someone had died. I held my breath and read as Dr. Jimmy Potash informed our entire department that Dr. Cait McFarland died in a car accident on December 7 while driving to work at West Cecil Health Center, Conowingo, Md., where she was director of psychiatry.

Sadness swelled as I remembered the outspoken resident who was interested in LGBTQ issues. Cait graduated from the Johns Hopkins residency program in 2020, she had recently married a social worker in the department, and the plan was for her to return to Hopkins full-time in July 2023 to be director of a clinic focused on mental health for people who are transgendered.

Sudden deaths are tragic and jarring and they call to the surface our losses from the past. These deaths don’t stand alone – I found myself thinking of my editor at Medscape, Dr. Bret Stetka, who died unexpectedly in August 2022, and then of Dr. Lidia Palcan Wenz, a psychiatrist I trained with, who died in a motor vehicle accident in 2004. Lidia’s husband also died in the accident, while their two young children in the back seat survived – this tragedy haunted me for some time. None of these people was close to me, but I am no stranger to the impact of unexpected death: My parents and brother all died from cardiac events, and any sudden death is a reminder of those losses.

Julia Riddle, MD, trained with Cait McFarland and was her close friend for years. “I don’t have a belief in ‘the afterlife’ but do like to think of the people that I have lost together in my memory – as if they are all suddenly in a new room together. And, with each loss, all the other occupants of that room come freshly to life again,” Dr. Riddle said.

Death is our shared destination in life, but sudden and unexpected deaths carry their own weight. There is no chance to tie up loose ends, to repair riffs, to say goodbye. Nothing is put in order, and the life that was to be lived goes on for some time as bills arrive, social and work events go unattended, vacations are canceled, and there is the awkward moment of running into someone who didn’t know your loved one has died.

Roger Lewin, MD, is a psychiatrist and writer in Towson, Md. He has both personal and professional experience with sudden death. “There is no way to prepare beforehand, so we have to get ready for what has already happened, and that is hard,” he said. “We invent a life for ourselves and others that extends into the future, and that gets interrupted.”

Most people become ill and die on a vaguely predictable schedule. There may be a chance to plan, to know and honor the wishes of the individual, and often there is the opportunity for loved ones to begin the grieving process gradually as death approaches. For those who are elderly, there may be a sense that this is the natural order of things – which may or may not temper the intensity of the grief for those who remain. If the person has suffered, the end may come with relief.

Still, I sometimes find myself surprised at the length and intensity of anguish that some people experience after losing a loved one who has lived a long and full life, who declined and suffered, but whose absence remains a gaping wound that takes years to form a scar.

Sudden death is not rare; accidents, homicide, and suicide are the top killers among young people, and cardiovascular deaths are number one among those who are older. Natural disasters and terrorist attacks can cause catastrophic numbers of sudden deaths and leave survivors to grieve not only the dead, but the loss of all that was familiar to them.

Psychiatry has been a bit lost as to how we approach grief. We often hear patients talk about anxiety surrounding death and illness, be it a fear of death or a longing for it. These fears can seem irrational – I am reminded of a patient who was afraid to eat romaine because of news reports that it was responsible for food poisoning in other states, but not Maryland, where the person lived. I found it odd that he worried about eating lettuce, but not about smoking two packs of cigarettes a day.

But our fears are like that – they move to what the media sensationalizes, or to what may be remote, because otherwise no one would get in a car or clear their walkway of snow. Life is most easily lived with a bit of denial: We shut out the reality that we can be here one moment, overscheduled and overwhelmed, with deadlines, mortgage payments, and summer vacation plans, oblivious to the fact that life may end at any moment. The early months of COVID-19 felt like a global game of Russian roulette, with each venture out a pull of the trigger and everyone’s defenses stripped bare.

While death belongs to us all, we relegate it to the disciplines of religion, philosophy, the arts, and psychology. Religion offers answers – whether a heaven, a hell, or continual reincarnation until the individual attains enlightenment, there is a destination. Perhaps it will be pleasant, perhaps not, and for some there is the hope that one gets to be the driver by having the right beliefs or doing good deeds, while others are comforted by the hope of being reunited with loved ones.

“The suddenness endures and the shock lasts – it’s like a meteor that creates a crater and we revisit it in different ways from different angles,” Dr. Lewin said. “It may leap on us unexpectedly, often many years later.”

Patients talk about death, and when their fears seem unrealistic we may long to reassure them, yet there is no reassurance and psychiatry grasps for how to help. Psychiatry has looked to draw lines for when normal grief crosses to abnormal. Is it an adjustment disorder, complicated grief, “prolonged” grief, pathology in need of medication and medicalization, or something one experiences individually, sometimes for a very long time even with treatment?

One justification for pathologizing “prolonged” reactions includes the fact that insurers will pay for treatment only if there is a diagnosis code, and shouldn’t people in distress be entitled to psychotherapy or medication? Yet there is something offensive about telling someone that they are mentally ill if they don’t grieve along a prescribed timeline, as much as there is about denying them the possible benefits of therapy or medication if they seek it, but are suffering in all the “right” ways. Psychiatry’s approach to death is inelegant at best.

In his poignant podcast series, All There Is, Anderson Cooper is tasked with sorting through his mother’s apartment after her death at age 95. In the course of packing up her belongings, he brings on other guests to talk about their emotional reactions to death. Mr. Cooper’s mother, Gloria Vanderbilt, died at an advanced age, but his father died after a brief cardiac illness when Mr. Cooper was a child, and his brother died by suicide when he was 21. He uses these experiences as a springboard to examine childhood losses, the aftermath of suicide, and the loneliness of grief.

“Loss and grief is this universal experience that we will all go through multiple times in our lives,” Mr. Cooper says, “And yet it leaves us feeling so alone and so separated from other people. At least it does me and has my entire life.”

When we talk about grief and loss, we talk about “getting over it,” or “moving on.” But loss doesn’t work that way – time usually eases the pain, leaving scars that are part of the road map for who we are on the journey that defines us.

Sudden death is hard, and the unexpected death of a young person is tragic. For Cait McFarland, there are the decades she won’t get to experience. For her family and friends, it may be excruciating, and for all the patients who have lost a psychiatrist, may time bring healing and peace.

The Dr. Caitlin McFarland Educational Fund for LGBTQI+ Mental Health is being established, and donations are being accepted at https://www.gofundme.com/f/in-memory-of-cait-mcfarland.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships.

“It is one of life’s most self-evident truths that everything fades, that we fear the fading, and that we must live, nonetheless, in the face of the fear.” – Irvin D. Yalom, MD, Existential Psychotherapy, 1980

The email was titled simply, “A sorrowful note,” and I knew that someone had died. I held my breath and read as Dr. Jimmy Potash informed our entire department that Dr. Cait McFarland died in a car accident on December 7 while driving to work at West Cecil Health Center, Conowingo, Md., where she was director of psychiatry.

Sadness swelled as I remembered the outspoken resident who was interested in LGBTQ issues. Cait graduated from the Johns Hopkins residency program in 2020, she had recently married a social worker in the department, and the plan was for her to return to Hopkins full-time in July 2023 to be director of a clinic focused on mental health for people who are transgendered.

Sudden deaths are tragic and jarring and they call to the surface our losses from the past. These deaths don’t stand alone – I found myself thinking of my editor at Medscape, Dr. Bret Stetka, who died unexpectedly in August 2022, and then of Dr. Lidia Palcan Wenz, a psychiatrist I trained with, who died in a motor vehicle accident in 2004. Lidia’s husband also died in the accident, while their two young children in the back seat survived – this tragedy haunted me for some time. None of these people was close to me, but I am no stranger to the impact of unexpected death: My parents and brother all died from cardiac events, and any sudden death is a reminder of those losses.

Julia Riddle, MD, trained with Cait McFarland and was her close friend for years. “I don’t have a belief in ‘the afterlife’ but do like to think of the people that I have lost together in my memory – as if they are all suddenly in a new room together. And, with each loss, all the other occupants of that room come freshly to life again,” Dr. Riddle said.

Death is our shared destination in life, but sudden and unexpected deaths carry their own weight. There is no chance to tie up loose ends, to repair riffs, to say goodbye. Nothing is put in order, and the life that was to be lived goes on for some time as bills arrive, social and work events go unattended, vacations are canceled, and there is the awkward moment of running into someone who didn’t know your loved one has died.

Roger Lewin, MD, is a psychiatrist and writer in Towson, Md. He has both personal and professional experience with sudden death. “There is no way to prepare beforehand, so we have to get ready for what has already happened, and that is hard,” he said. “We invent a life for ourselves and others that extends into the future, and that gets interrupted.”

Most people become ill and die on a vaguely predictable schedule. There may be a chance to plan, to know and honor the wishes of the individual, and often there is the opportunity for loved ones to begin the grieving process gradually as death approaches. For those who are elderly, there may be a sense that this is the natural order of things – which may or may not temper the intensity of the grief for those who remain. If the person has suffered, the end may come with relief.

Still, I sometimes find myself surprised at the length and intensity of anguish that some people experience after losing a loved one who has lived a long and full life, who declined and suffered, but whose absence remains a gaping wound that takes years to form a scar.

Sudden death is not rare; accidents, homicide, and suicide are the top killers among young people, and cardiovascular deaths are number one among those who are older. Natural disasters and terrorist attacks can cause catastrophic numbers of sudden deaths and leave survivors to grieve not only the dead, but the loss of all that was familiar to them.

Psychiatry has been a bit lost as to how we approach grief. We often hear patients talk about anxiety surrounding death and illness, be it a fear of death or a longing for it. These fears can seem irrational – I am reminded of a patient who was afraid to eat romaine because of news reports that it was responsible for food poisoning in other states, but not Maryland, where the person lived. I found it odd that he worried about eating lettuce, but not about smoking two packs of cigarettes a day.

But our fears are like that – they move to what the media sensationalizes, or to what may be remote, because otherwise no one would get in a car or clear their walkway of snow. Life is most easily lived with a bit of denial: We shut out the reality that we can be here one moment, overscheduled and overwhelmed, with deadlines, mortgage payments, and summer vacation plans, oblivious to the fact that life may end at any moment. The early months of COVID-19 felt like a global game of Russian roulette, with each venture out a pull of the trigger and everyone’s defenses stripped bare.

While death belongs to us all, we relegate it to the disciplines of religion, philosophy, the arts, and psychology. Religion offers answers – whether a heaven, a hell, or continual reincarnation until the individual attains enlightenment, there is a destination. Perhaps it will be pleasant, perhaps not, and for some there is the hope that one gets to be the driver by having the right beliefs or doing good deeds, while others are comforted by the hope of being reunited with loved ones.

“The suddenness endures and the shock lasts – it’s like a meteor that creates a crater and we revisit it in different ways from different angles,” Dr. Lewin said. “It may leap on us unexpectedly, often many years later.”

Patients talk about death, and when their fears seem unrealistic we may long to reassure them, yet there is no reassurance and psychiatry grasps for how to help. Psychiatry has looked to draw lines for when normal grief crosses to abnormal. Is it an adjustment disorder, complicated grief, “prolonged” grief, pathology in need of medication and medicalization, or something one experiences individually, sometimes for a very long time even with treatment?

One justification for pathologizing “prolonged” reactions includes the fact that insurers will pay for treatment only if there is a diagnosis code, and shouldn’t people in distress be entitled to psychotherapy or medication? Yet there is something offensive about telling someone that they are mentally ill if they don’t grieve along a prescribed timeline, as much as there is about denying them the possible benefits of therapy or medication if they seek it, but are suffering in all the “right” ways. Psychiatry’s approach to death is inelegant at best.

In his poignant podcast series, All There Is, Anderson Cooper is tasked with sorting through his mother’s apartment after her death at age 95. In the course of packing up her belongings, he brings on other guests to talk about their emotional reactions to death. Mr. Cooper’s mother, Gloria Vanderbilt, died at an advanced age, but his father died after a brief cardiac illness when Mr. Cooper was a child, and his brother died by suicide when he was 21. He uses these experiences as a springboard to examine childhood losses, the aftermath of suicide, and the loneliness of grief.

“Loss and grief is this universal experience that we will all go through multiple times in our lives,” Mr. Cooper says, “And yet it leaves us feeling so alone and so separated from other people. At least it does me and has my entire life.”

When we talk about grief and loss, we talk about “getting over it,” or “moving on.” But loss doesn’t work that way – time usually eases the pain, leaving scars that are part of the road map for who we are on the journey that defines us.

Sudden death is hard, and the unexpected death of a young person is tragic. For Cait McFarland, there are the decades she won’t get to experience. For her family and friends, it may be excruciating, and for all the patients who have lost a psychiatrist, may time bring healing and peace.

The Dr. Caitlin McFarland Educational Fund for LGBTQI+ Mental Health is being established, and donations are being accepted at https://www.gofundme.com/f/in-memory-of-cait-mcfarland.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships.

In this era of efficacious treatments for mantle cell lymphoma (MCL), patients who survive 2 years sans disease recurrence or progression live nearly as long as age- and sex-matched individuals in the general population, a recent study showed.

Patients with MCL who achieved this endpoint – event-free survival at 24 months (EFS24) – also had a low risk of lymphoma-related death, and most often died from unrelated causes, according to results of the prospective cohort study.

Although longer follow-up and confirmation from other study groups are needed, these findings demonstrated a prognostic role for EFS24 in patients with mantle cell lymphoma, according to the lead author, Yucai Wang, MD, PhD, a hematologist/oncologist with Mayo Clinic in Rochester, Minn.

As more effective therapies emerge, overall survival (OS) will likely continue to improve, such that EFS24 will may become an important clinical endpoint in MCL frontline therapy, according to Dr. Wang.

“When we counseled patients with newly diagnosed MCL, we used to tell them that this is an aggressive and incurable disease, and patients would feel bad about it, “ Dr. Wang said in an interview.

“Now that we have better therapy, and outcomes are improving,” he continued, “I think it’s important to tell our patients now that we have improved outcomes for patients with this disease, and things are probably going to get better in the future, to always remain hopeful. That’s powerful for our patients to know.”
 

Two eras of treatment

The current analysis by Dr. Wang and colleagues was based on patients identified in the Lymphoma Specialized Program of Research Excellence Molecular Epidemiology Resource Cohort Study, a prospective observational study of lymphoma patients evaluated at the Mayo Clinic and the University of Iowa.

The patients were divided into two “eras” of treatment, based on the date of enrollment. Era 1 of enrollment was 2002 to 2009, and Era 2 was 2010 to 2015.

Patients in Era 2 had a substantially improved EFS and OS compared with those in Era 1, according to a previous report from Dr. Wang and coauthors.

Those improved treatment outcomes were likely due to advances in frontline immunochemotherapy, the authors said in that report. In particular, they pointed to the use of highly effective induction regimens containing high-dose cytarabine in patients who were eligible for autologous stem cell transplantation, and the combined use of rituximab-bendamustine in patients who were not eligible for transplant.

In addition, the increased use of salvage treatments such as lenalidomide and Bruton’s tyrosine kinase inhibitors has likely contributed to improvements in outcomes across eras, Dr. Wang and coauthors said in the present report, which looks more closely at the prognostic role of the EFS24 endpoint in Era 1 and Era 2 patients.

The five-year OS for patients diagnosed in Era 2 was 68.4%, compared with 59.2% in Era 1, the authors reported.

Achieving 2 years of EFS had no impact on OS in the earlier era, their findings further show.

In Era 1, the 98 patients who achieved EFS24 went on to have inferior OS compared with the general population, while in Era 2, the 99 patients achieving EFS24 had similar OS compared with the general population.

This was reported as a standardized mortality ratio (SMR) in Era 1 of 2.23 (95% confidence interval, 1.67-2.92; P < .001). By contrast, the SMR in Era 2 was just 1.31 (95% CI, 0.78-2.07; P = .31).

The risk of dying from lymphoma was lower among patients achieving EFS24 in the more recent Era 2, the results showed.

Among patients in Era 1 achieving EFS24, the primary cause of death was lymphoma-related, and the 5-year rate of lymphoma-related death was 19.8%, versus 6.2% for causes of death unrelated to lymphoma.

By contrast, among patients in Era 2 achieving EFS24, the 5-year rate of lymphoma-related death was 2.1% and 5.5% for other causes.
 

Favorable prognosis

These findings clearly showed that in one cohort of patients with MCL treated in the recent past, those patients going 2 years without evidence of disease progression or events “have a great prognosis,” said Matthew Matasar, MD, MS, chief of blood disorders, Rutgers Cancer Institute of New Jersey and RWJBarnabas Health.

However, there are limitations to describing the role of EFS24 in MCL based solely on this single-cohort study, Dr. Matasar said in an interview.

“There’s a lot of heterogeneity in how we treat mantle cell lymphoma,” he said, “so I would just caution generalizing out of a patient population treated one way to populations that may receive quite different therapeutic approaches.”

Dr. Wang said he and his coinvestigators have several confirmatory studies in the works that are focused on other groups of patients both inside and outside the United States, to validate of EFS24 as an endpoint.

“We have at least four cohorts to look into this and see whether we can see the same or similar results,” he said in the interview.

Dr. Wang disclosed ties with Incyte, InnoCare, LOXO Oncology, Novartis, Genentech, Eli Lilly, TG Therapeutics, MorphoSys, Genmab, and Kite.

In this era of efficacious treatments for mantle cell lymphoma (MCL), patients who survive 2 years sans disease recurrence or progression live nearly as long as age- and sex-matched individuals in the general population, a recent study showed.

Patients with MCL who achieved this endpoint – event-free survival at 24 months (EFS24) – also had a low risk of lymphoma-related death, and most often died from unrelated causes, according to results of the prospective cohort study.

Although longer follow-up and confirmation from other study groups are needed, these findings demonstrated a prognostic role for EFS24 in patients with mantle cell lymphoma, according to the lead author, Yucai Wang, MD, PhD, a hematologist/oncologist with Mayo Clinic in Rochester, Minn.

As more effective therapies emerge, overall survival (OS) will likely continue to improve, such that EFS24 will may become an important clinical endpoint in MCL frontline therapy, according to Dr. Wang.

“When we counseled patients with newly diagnosed MCL, we used to tell them that this is an aggressive and incurable disease, and patients would feel bad about it, “ Dr. Wang said in an interview.

“Now that we have better therapy, and outcomes are improving,” he continued, “I think it’s important to tell our patients now that we have improved outcomes for patients with this disease, and things are probably going to get better in the future, to always remain hopeful. That’s powerful for our patients to know.”
 

Two eras of treatment

The current analysis by Dr. Wang and colleagues was based on patients identified in the Lymphoma Specialized Program of Research Excellence Molecular Epidemiology Resource Cohort Study, a prospective observational study of lymphoma patients evaluated at the Mayo Clinic and the University of Iowa.

The patients were divided into two “eras” of treatment, based on the date of enrollment. Era 1 of enrollment was 2002 to 2009, and Era 2 was 2010 to 2015.

Patients in Era 2 had a substantially improved EFS and OS compared with those in Era 1, according to a previous report from Dr. Wang and coauthors.

Those improved treatment outcomes were likely due to advances in frontline immunochemotherapy, the authors said in that report. In particular, they pointed to the use of highly effective induction regimens containing high-dose cytarabine in patients who were eligible for autologous stem cell transplantation, and the combined use of rituximab-bendamustine in patients who were not eligible for transplant.

In addition, the increased use of salvage treatments such as lenalidomide and Bruton’s tyrosine kinase inhibitors has likely contributed to improvements in outcomes across eras, Dr. Wang and coauthors said in the present report, which looks more closely at the prognostic role of the EFS24 endpoint in Era 1 and Era 2 patients.

The five-year OS for patients diagnosed in Era 2 was 68.4%, compared with 59.2% in Era 1, the authors reported.

Achieving 2 years of EFS had no impact on OS in the earlier era, their findings further show.

In Era 1, the 98 patients who achieved EFS24 went on to have inferior OS compared with the general population, while in Era 2, the 99 patients achieving EFS24 had similar OS compared with the general population.

This was reported as a standardized mortality ratio (SMR) in Era 1 of 2.23 (95% confidence interval, 1.67-2.92; P < .001). By contrast, the SMR in Era 2 was just 1.31 (95% CI, 0.78-2.07; P = .31).

The risk of dying from lymphoma was lower among patients achieving EFS24 in the more recent Era 2, the results showed.

Among patients in Era 1 achieving EFS24, the primary cause of death was lymphoma-related, and the 5-year rate of lymphoma-related death was 19.8%, versus 6.2% for causes of death unrelated to lymphoma.

By contrast, among patients in Era 2 achieving EFS24, the 5-year rate of lymphoma-related death was 2.1% and 5.5% for other causes.
 

Favorable prognosis

These findings clearly showed that in one cohort of patients with MCL treated in the recent past, those patients going 2 years without evidence of disease progression or events “have a great prognosis,” said Matthew Matasar, MD, MS, chief of blood disorders, Rutgers Cancer Institute of New Jersey and RWJBarnabas Health.

However, there are limitations to describing the role of EFS24 in MCL based solely on this single-cohort study, Dr. Matasar said in an interview.

“There’s a lot of heterogeneity in how we treat mantle cell lymphoma,” he said, “so I would just caution generalizing out of a patient population treated one way to populations that may receive quite different therapeutic approaches.”

Dr. Wang said he and his coinvestigators have several confirmatory studies in the works that are focused on other groups of patients both inside and outside the United States, to validate of EFS24 as an endpoint.

“We have at least four cohorts to look into this and see whether we can see the same or similar results,” he said in the interview.

Dr. Wang disclosed ties with Incyte, InnoCare, LOXO Oncology, Novartis, Genentech, Eli Lilly, TG Therapeutics, MorphoSys, Genmab, and Kite.

In this era of efficacious treatments for mantle cell lymphoma (MCL), patients who survive 2 years sans disease recurrence or progression live nearly as long as age- and sex-matched individuals in the general population, a recent study showed.

Patients with MCL who achieved this endpoint – event-free survival at 24 months (EFS24) – also had a low risk of lymphoma-related death, and most often died from unrelated causes, according to results of the prospective cohort study.

Although longer follow-up and confirmation from other study groups are needed, these findings demonstrated a prognostic role for EFS24 in patients with mantle cell lymphoma, according to the lead author, Yucai Wang, MD, PhD, a hematologist/oncologist with Mayo Clinic in Rochester, Minn.

As more effective therapies emerge, overall survival (OS) will likely continue to improve, such that EFS24 will may become an important clinical endpoint in MCL frontline therapy, according to Dr. Wang.

“When we counseled patients with newly diagnosed MCL, we used to tell them that this is an aggressive and incurable disease, and patients would feel bad about it, “ Dr. Wang said in an interview.

“Now that we have better therapy, and outcomes are improving,” he continued, “I think it’s important to tell our patients now that we have improved outcomes for patients with this disease, and things are probably going to get better in the future, to always remain hopeful. That’s powerful for our patients to know.”
 

Two eras of treatment

The current analysis by Dr. Wang and colleagues was based on patients identified in the Lymphoma Specialized Program of Research Excellence Molecular Epidemiology Resource Cohort Study, a prospective observational study of lymphoma patients evaluated at the Mayo Clinic and the University of Iowa.

The patients were divided into two “eras” of treatment, based on the date of enrollment. Era 1 of enrollment was 2002 to 2009, and Era 2 was 2010 to 2015.

Patients in Era 2 had a substantially improved EFS and OS compared with those in Era 1, according to a previous report from Dr. Wang and coauthors.

Those improved treatment outcomes were likely due to advances in frontline immunochemotherapy, the authors said in that report. In particular, they pointed to the use of highly effective induction regimens containing high-dose cytarabine in patients who were eligible for autologous stem cell transplantation, and the combined use of rituximab-bendamustine in patients who were not eligible for transplant.

In addition, the increased use of salvage treatments such as lenalidomide and Bruton’s tyrosine kinase inhibitors has likely contributed to improvements in outcomes across eras, Dr. Wang and coauthors said in the present report, which looks more closely at the prognostic role of the EFS24 endpoint in Era 1 and Era 2 patients.

The five-year OS for patients diagnosed in Era 2 was 68.4%, compared with 59.2% in Era 1, the authors reported.

Achieving 2 years of EFS had no impact on OS in the earlier era, their findings further show.

In Era 1, the 98 patients who achieved EFS24 went on to have inferior OS compared with the general population, while in Era 2, the 99 patients achieving EFS24 had similar OS compared with the general population.

This was reported as a standardized mortality ratio (SMR) in Era 1 of 2.23 (95% confidence interval, 1.67-2.92; P < .001). By contrast, the SMR in Era 2 was just 1.31 (95% CI, 0.78-2.07; P = .31).

The risk of dying from lymphoma was lower among patients achieving EFS24 in the more recent Era 2, the results showed.

Among patients in Era 1 achieving EFS24, the primary cause of death was lymphoma-related, and the 5-year rate of lymphoma-related death was 19.8%, versus 6.2% for causes of death unrelated to lymphoma.

By contrast, among patients in Era 2 achieving EFS24, the 5-year rate of lymphoma-related death was 2.1% and 5.5% for other causes.
 

Favorable prognosis

These findings clearly showed that in one cohort of patients with MCL treated in the recent past, those patients going 2 years without evidence of disease progression or events “have a great prognosis,” said Matthew Matasar, MD, MS, chief of blood disorders, Rutgers Cancer Institute of New Jersey and RWJBarnabas Health.

However, there are limitations to describing the role of EFS24 in MCL based solely on this single-cohort study, Dr. Matasar said in an interview.

“There’s a lot of heterogeneity in how we treat mantle cell lymphoma,” he said, “so I would just caution generalizing out of a patient population treated one way to populations that may receive quite different therapeutic approaches.”

Dr. Wang said he and his coinvestigators have several confirmatory studies in the works that are focused on other groups of patients both inside and outside the United States, to validate of EFS24 as an endpoint.

“We have at least four cohorts to look into this and see whether we can see the same or similar results,” he said in the interview.

Dr. Wang disclosed ties with Incyte, InnoCare, LOXO Oncology, Novartis, Genentech, Eli Lilly, TG Therapeutics, MorphoSys, Genmab, and Kite.

Higher fat-free mass was tied to exercise outcomes in patients with chronic obstructive pulmonary disease who were underweight but not in those who were obese or nearly obese, based on data from more than 2,000 individuals.

Change in body composition, including a lower fat-free mass index (FFMI), often occurs in patients with COPD irrespective of body weight, write Felipe V.C. Machado, MSc, of Maastricht University Medical Center, the Netherlands, and colleagues.

However, the impact of changes in FFMI on outcomes including exercise capacity, health-related quality of life (HRQL), and systemic inflammation in patients with COPD stratified by BMI has not been well studied, they said.

In a study published in the journal CHEST, the researchers reviewed data from the COPD and Systemic Consequences – Comorbidities Network (COSYCONET) cohort. The study population included 2,137 adults with COPD (mean age 65 years; 61% men). Patients were divided into four groups based on weight: underweight (UW), normal weight (NW), pre-obese (PO), and obese (OB). These groups accounted for 12.3%, 31.3%, 39.6%, and 16.8%, respectively, of the study population.

Exercise capacity was assessed using the 6-minute walk distance test (6MWD), health-related quality of life was assessed using the Saint George’s Respiratory Questionnaire for COPD, and systemic inflammation was assessed using blood markers including white blood cell (WBC) count and C-reactive protein (CRP). Body composition was assessed using bioelectrical impedance analysis (BIA).

Overall, the frequency of low FFMI decreased from lower to higher BMI groups, occurring in 81% of UW patients, 53% of NW patients, 42% of PO patients, and 39% of OB patients.

Notably, after adjusting for multiple variables, FFM was independently associated with improved scores on the 6-minute walk test for UW patients; NW and PO patients had no such association after controlling for lung function (forced expiratory volume in 1 second – FEV1), the researchers wrote.

However, compared with the other BMI groups, NW patients with high FFMI showed the greatest exercise capacity and health-related quality of life on average, with the lowest degree of airflow limitation (FEV1, 59.5), lowest proportion of patients with mMRC greater than 2 (27%), highest levels of physical activity (International Physical Activity Questionnaire score), best exercise capacity (6MWD, 77) and highest HRQL (SGRQ total score 37).

Body composition was associated differently with exercise capacity, HRQL, and systemic inflammation according to BMI group, the researchers write in their discussion. “We found that stratification using BMI allowed discrimination of groups of patients with COPD who showed slight but significant differences in lung function, exercise capacity, HRQL and systemic inflammation,” they say.

The findings were limited by several factors, including the use of BIA for body composition, which may be subject to hydration and fed conditions, the researchers noted. Other limitations included the use of reference values from a general population sample younger than much of the study population and the cross-sectional design that does not prove causality, the researchers noted.

However, the results support those of previous studies and suggest that normal weight and high FFMI is the most favorable combination to promote positive outcomes in COPD, they conclude. “Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone,” they say.

The COSYCONET study is supported by the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET) in collaboration with the German Center for Lung Research (DZL). The study also was funded by AstraZeneca, Bayer Schering Pharma AG, Boehringer Ingelheim Pharma, Chiesi, GlaxoSmithKline, and multiple other pharmaceutical companies.

Mr. Machado disclosed financial support from ZonMW.  

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

Higher fat-free mass was tied to exercise outcomes in patients with chronic obstructive pulmonary disease who were underweight but not in those who were obese or nearly obese, based on data from more than 2,000 individuals.

Change in body composition, including a lower fat-free mass index (FFMI), often occurs in patients with COPD irrespective of body weight, write Felipe V.C. Machado, MSc, of Maastricht University Medical Center, the Netherlands, and colleagues.

However, the impact of changes in FFMI on outcomes including exercise capacity, health-related quality of life (HRQL), and systemic inflammation in patients with COPD stratified by BMI has not been well studied, they said.

In a study published in the journal CHEST, the researchers reviewed data from the COPD and Systemic Consequences – Comorbidities Network (COSYCONET) cohort. The study population included 2,137 adults with COPD (mean age 65 years; 61% men). Patients were divided into four groups based on weight: underweight (UW), normal weight (NW), pre-obese (PO), and obese (OB). These groups accounted for 12.3%, 31.3%, 39.6%, and 16.8%, respectively, of the study population.

Exercise capacity was assessed using the 6-minute walk distance test (6MWD), health-related quality of life was assessed using the Saint George’s Respiratory Questionnaire for COPD, and systemic inflammation was assessed using blood markers including white blood cell (WBC) count and C-reactive protein (CRP). Body composition was assessed using bioelectrical impedance analysis (BIA).

Overall, the frequency of low FFMI decreased from lower to higher BMI groups, occurring in 81% of UW patients, 53% of NW patients, 42% of PO patients, and 39% of OB patients.

Notably, after adjusting for multiple variables, FFM was independently associated with improved scores on the 6-minute walk test for UW patients; NW and PO patients had no such association after controlling for lung function (forced expiratory volume in 1 second – FEV1), the researchers wrote.

However, compared with the other BMI groups, NW patients with high FFMI showed the greatest exercise capacity and health-related quality of life on average, with the lowest degree of airflow limitation (FEV1, 59.5), lowest proportion of patients with mMRC greater than 2 (27%), highest levels of physical activity (International Physical Activity Questionnaire score), best exercise capacity (6MWD, 77) and highest HRQL (SGRQ total score 37).

Body composition was associated differently with exercise capacity, HRQL, and systemic inflammation according to BMI group, the researchers write in their discussion. “We found that stratification using BMI allowed discrimination of groups of patients with COPD who showed slight but significant differences in lung function, exercise capacity, HRQL and systemic inflammation,” they say.

The findings were limited by several factors, including the use of BIA for body composition, which may be subject to hydration and fed conditions, the researchers noted. Other limitations included the use of reference values from a general population sample younger than much of the study population and the cross-sectional design that does not prove causality, the researchers noted.

However, the results support those of previous studies and suggest that normal weight and high FFMI is the most favorable combination to promote positive outcomes in COPD, they conclude. “Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone,” they say.

The COSYCONET study is supported by the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET) in collaboration with the German Center for Lung Research (DZL). The study also was funded by AstraZeneca, Bayer Schering Pharma AG, Boehringer Ingelheim Pharma, Chiesi, GlaxoSmithKline, and multiple other pharmaceutical companies.

Mr. Machado disclosed financial support from ZonMW.  

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

Higher fat-free mass was tied to exercise outcomes in patients with chronic obstructive pulmonary disease who were underweight but not in those who were obese or nearly obese, based on data from more than 2,000 individuals.

Change in body composition, including a lower fat-free mass index (FFMI), often occurs in patients with COPD irrespective of body weight, write Felipe V.C. Machado, MSc, of Maastricht University Medical Center, the Netherlands, and colleagues.

However, the impact of changes in FFMI on outcomes including exercise capacity, health-related quality of life (HRQL), and systemic inflammation in patients with COPD stratified by BMI has not been well studied, they said.

In a study published in the journal CHEST, the researchers reviewed data from the COPD and Systemic Consequences – Comorbidities Network (COSYCONET) cohort. The study population included 2,137 adults with COPD (mean age 65 years; 61% men). Patients were divided into four groups based on weight: underweight (UW), normal weight (NW), pre-obese (PO), and obese (OB). These groups accounted for 12.3%, 31.3%, 39.6%, and 16.8%, respectively, of the study population.

Exercise capacity was assessed using the 6-minute walk distance test (6MWD), health-related quality of life was assessed using the Saint George’s Respiratory Questionnaire for COPD, and systemic inflammation was assessed using blood markers including white blood cell (WBC) count and C-reactive protein (CRP). Body composition was assessed using bioelectrical impedance analysis (BIA).

Overall, the frequency of low FFMI decreased from lower to higher BMI groups, occurring in 81% of UW patients, 53% of NW patients, 42% of PO patients, and 39% of OB patients.

Notably, after adjusting for multiple variables, FFM was independently associated with improved scores on the 6-minute walk test for UW patients; NW and PO patients had no such association after controlling for lung function (forced expiratory volume in 1 second – FEV1), the researchers wrote.

However, compared with the other BMI groups, NW patients with high FFMI showed the greatest exercise capacity and health-related quality of life on average, with the lowest degree of airflow limitation (FEV1, 59.5), lowest proportion of patients with mMRC greater than 2 (27%), highest levels of physical activity (International Physical Activity Questionnaire score), best exercise capacity (6MWD, 77) and highest HRQL (SGRQ total score 37).

Body composition was associated differently with exercise capacity, HRQL, and systemic inflammation according to BMI group, the researchers write in their discussion. “We found that stratification using BMI allowed discrimination of groups of patients with COPD who showed slight but significant differences in lung function, exercise capacity, HRQL and systemic inflammation,” they say.

The findings were limited by several factors, including the use of BIA for body composition, which may be subject to hydration and fed conditions, the researchers noted. Other limitations included the use of reference values from a general population sample younger than much of the study population and the cross-sectional design that does not prove causality, the researchers noted.

However, the results support those of previous studies and suggest that normal weight and high FFMI is the most favorable combination to promote positive outcomes in COPD, they conclude. “Clinicians and researchers should consider screening patients with COPD for body composition abnormalities through a combination of BMI and FFMI classifications rather than each of the two indexes alone,” they say.

The COSYCONET study is supported by the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET) in collaboration with the German Center for Lung Research (DZL). The study also was funded by AstraZeneca, Bayer Schering Pharma AG, Boehringer Ingelheim Pharma, Chiesi, GlaxoSmithKline, and multiple other pharmaceutical companies.

Mr. Machado disclosed financial support from ZonMW.  

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