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Hematology is in the Brodsky family’s blood
In interviews, Robert and Max Brodsky spoke about the appeal of hematology and the threads that unite them with family members who came before. The elder Brodsky also talked about the work that’s made him the proudest during his year-long presidency at ASH.
Robert A. Brodsky is professor of medicine and director of hematology at Johns Hopkins University, Baltimore. He is stepping down as ASH president at its annual meeting in San Diego, December 9-12. Here are excerpts from our conversation:
Q: What drew your dad into medicine?
Dr. Robert A. Brodsky: He was going through his medical training at the University of Pennsylvania, then the Vietnam War came, and he served at the National Institutes of Health in what they referred to as the Yellow Berets. He got very interested in retroviruses and viruses that lead to cancer, which was a foreign idea at the time. This led him into hematology, stem cells, and myeloproliferative disorders.
He had a very successful career in hematology and just loved it. He performed the first bone marrow transplant in the tristate area of Pennsylvania, Delaware, and New Jersey.
Q: What did he like about hematology specifically?
Dr. Robert A. Brodsky: It’s a fascinating field, probably the most scientific area of medicine. It’s so easy to access blood and bone marrow. You can grow it, you can look at it, you can see it. It’s hard to do that with a lung, heart, kidney, or brain. Even back then, they could translate some of the science. What really drew him to hematology — and me, for that matter — was looking at a blood smear or bone marrow and being able to make a diagnosis. The other thing is the personal aspect. Hematologists tend to like the long-term relationships that they develop with their patients over the years.
Q: What were the biggest transformations in hematology during his career?
Dr. Robert A. Brodsky: Bone marrow transplant had the biggest impact, and it’s an area he really pioneered. He was very much involved in some of the early bone marrow transplants and was very close with Dr. George W. Santos, who was at Johns Hopkins and one of the big pioneers in that area as well. To be able to take marrow from related donors, get it to grow without the patient rejecting it, and cure a disease, was really huge. When he started doing this, patients had no other option. To see patients be cured was incredibly satisfying to him.
Q: How did you end up following your father into hematology?
Dr. Robert A. Brodsky: My brother Jeff, who’s a surgeon and older than me, knew he was going into medicine — probably about 3 hours after he was born. I came to it late. I was a political science major as an undergrad and really trying to figure out what I wanted to do. In my sophomore year, I decided I wanted to give this a shot. My dad worked very hard, long hours, but you could tell he loved what he did. And he was never absent, always involved in our lives and still made time for everyone. At some level, that must have had an influence on me.
Q: What has changed in hematology over your 30-plus years in medicine?
A: When I look back at when I was a fellow, it’s just mind-boggling how many lethal or life-threatening diseases are now pretty easy to treat. I studied disorders like aplastic anemia, which was very fatal. Without treatment, patients would die within a year. Now, over 95% are cured. Another classic examples is chronic myeloid leukemia disorder. Back when I was a fellow, the median survival for CML was maybe 4 to 6 years. Now, Kareem Abdul Jabbar has had this[for about 15 years]. Also a lot of hematologic malignancies are being cured with immunotherapy approaches. We’ve figured out the pathophysiology of a lot of diseases, and there are incredible genetic diagnostic assays.
Q: What was your father’s relationship with ASH?
Dr. Robert A. Brodsky: The first ASH meeting was 1958 in Atlantic City, New Jersey. There were 300 hematologists there, and my dad was one of them. We’re going to have over 30,000 people in San Diego, which is a record, and another 5,000 or 6,000 virtually.
Q: As ASH president, what are your biggest accomplishments when it comes to addressing the shortage of hematologists and other issues?
Dr. Robert A. Brodsky: ASH is investing $19 million to develop fellowships with a focus on hematology.* This is going to put lots of new hematologists into the workforce over the next 5 to 10 years. We’ve also been working on the Maintenance of Certification [MOC] process to make it less onerous on physicians. It’s really a bad process, and it’s not just ASH [that’s complaining], it’s all of medicine. We’re hearing this from GI, endocrine, renal and the general internists.
[In a September 2023 letter to the American Board of Internal Medicine’s president and chief officer, Dr. Brodsky wrote that “ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program.” ASH is calling for a new and reformed MOC program.]
Q: What convinced ASH to expand its journals by adding Blood Neoplasia and Blood Vessels, Thrombosis & Hemostasis?
Dr. Robert A. Brodsky: ASH has two flagship journals right now, Blood and Blood Advances, and they’re both very competitive, high-impact journals. It turns out there’s not enough room to publish all the new science, and they end up rejecting the majority of the submissions that come to them. We decided to keep these journals in the ASH family because there’s some fantastic clinical trials and science that would be going elsewhere.
Dr. Brodsky’s sons both have medical degrees: Brett Brodsky, DO, is a resident at Virginia Commonwealth University who plans to become a sports medicine specialist, and Max Brodsky, MD, is a second-year fellow in hematology at Johns Hopkins University.
In an interview, Max Brodsky, MD, talked about the roots of his family’s dedication to caring for others.
Q: What drew you to hematology?
Dr. Max Brodsky: I’ve watched both my dad and my grandfather be leaders in the field as both physicians and scientists, and that was very inspirational for me to see. And I went to a medical school [Drexel University College of Medicine] that my dad went to and where my grandfather was on faculty. That was like walking in their footsteps in a major way.
Q: What do you hope to focus on as a hematologist?
Dr. Max Brodsky: I’m still working through that, but I am really interested in thrombotic thrombocytopenic purpura. Patients used to not be able to survive their initial episodes, but now we have good treatments and are able to follow them as outpatients. With this whole cohort of patients that are surviving, we’re seeing that they have more health problems — more heart disease, more strokes and kidney disease. There’s a whole growing field exploring how to treat these patients for their lifespan.
Q: How do you deal with the reality that more of your patients will die than in some other medical fields?
Dr. Max Brodsky: It is challenging, but I also see those moments as opportunities to support patients and families. I’m good at connecting to patients and families who are in scary situations. I’ve always had that skill of putting people at ease, making people feel calm, knowing that they can trust me, and I have their best interests in mind.
Q: Why do you think your family is so committed to medicine?
Dr. Max Brodsky: We’re Jewish, and looking to help the world is one of the main core values of Judaism. The Torah expects us to make this world better. Actually, my great-grandfather Max, whom I’m named after, used to dig tunnels to help people escape Ukraine and get to freedom. He was always looking to help others as well. My great-grandmother was shot crossing the border escaping from Ukraine, and he carried her the whole way to the boat. They lived in very poor West Philadelphia and poured everything into my grandfather. He became a great doctor, and his sons and his grandchildren are in medicine today.
*Correction, 12/11: A previous version of this story misstated the amount of ASH’s $19 million investment in developing fellowships with a focus on hematology.
In interviews, Robert and Max Brodsky spoke about the appeal of hematology and the threads that unite them with family members who came before. The elder Brodsky also talked about the work that’s made him the proudest during his year-long presidency at ASH.
Robert A. Brodsky is professor of medicine and director of hematology at Johns Hopkins University, Baltimore. He is stepping down as ASH president at its annual meeting in San Diego, December 9-12. Here are excerpts from our conversation:
Q: What drew your dad into medicine?
Dr. Robert A. Brodsky: He was going through his medical training at the University of Pennsylvania, then the Vietnam War came, and he served at the National Institutes of Health in what they referred to as the Yellow Berets. He got very interested in retroviruses and viruses that lead to cancer, which was a foreign idea at the time. This led him into hematology, stem cells, and myeloproliferative disorders.
He had a very successful career in hematology and just loved it. He performed the first bone marrow transplant in the tristate area of Pennsylvania, Delaware, and New Jersey.
Q: What did he like about hematology specifically?
Dr. Robert A. Brodsky: It’s a fascinating field, probably the most scientific area of medicine. It’s so easy to access blood and bone marrow. You can grow it, you can look at it, you can see it. It’s hard to do that with a lung, heart, kidney, or brain. Even back then, they could translate some of the science. What really drew him to hematology — and me, for that matter — was looking at a blood smear or bone marrow and being able to make a diagnosis. The other thing is the personal aspect. Hematologists tend to like the long-term relationships that they develop with their patients over the years.
Q: What were the biggest transformations in hematology during his career?
Dr. Robert A. Brodsky: Bone marrow transplant had the biggest impact, and it’s an area he really pioneered. He was very much involved in some of the early bone marrow transplants and was very close with Dr. George W. Santos, who was at Johns Hopkins and one of the big pioneers in that area as well. To be able to take marrow from related donors, get it to grow without the patient rejecting it, and cure a disease, was really huge. When he started doing this, patients had no other option. To see patients be cured was incredibly satisfying to him.
Q: How did you end up following your father into hematology?
Dr. Robert A. Brodsky: My brother Jeff, who’s a surgeon and older than me, knew he was going into medicine — probably about 3 hours after he was born. I came to it late. I was a political science major as an undergrad and really trying to figure out what I wanted to do. In my sophomore year, I decided I wanted to give this a shot. My dad worked very hard, long hours, but you could tell he loved what he did. And he was never absent, always involved in our lives and still made time for everyone. At some level, that must have had an influence on me.
Q: What has changed in hematology over your 30-plus years in medicine?
A: When I look back at when I was a fellow, it’s just mind-boggling how many lethal or life-threatening diseases are now pretty easy to treat. I studied disorders like aplastic anemia, which was very fatal. Without treatment, patients would die within a year. Now, over 95% are cured. Another classic examples is chronic myeloid leukemia disorder. Back when I was a fellow, the median survival for CML was maybe 4 to 6 years. Now, Kareem Abdul Jabbar has had this[for about 15 years]. Also a lot of hematologic malignancies are being cured with immunotherapy approaches. We’ve figured out the pathophysiology of a lot of diseases, and there are incredible genetic diagnostic assays.
Q: What was your father’s relationship with ASH?
Dr. Robert A. Brodsky: The first ASH meeting was 1958 in Atlantic City, New Jersey. There were 300 hematologists there, and my dad was one of them. We’re going to have over 30,000 people in San Diego, which is a record, and another 5,000 or 6,000 virtually.
Q: As ASH president, what are your biggest accomplishments when it comes to addressing the shortage of hematologists and other issues?
Dr. Robert A. Brodsky: ASH is investing $19 million to develop fellowships with a focus on hematology.* This is going to put lots of new hematologists into the workforce over the next 5 to 10 years. We’ve also been working on the Maintenance of Certification [MOC] process to make it less onerous on physicians. It’s really a bad process, and it’s not just ASH [that’s complaining], it’s all of medicine. We’re hearing this from GI, endocrine, renal and the general internists.
[In a September 2023 letter to the American Board of Internal Medicine’s president and chief officer, Dr. Brodsky wrote that “ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program.” ASH is calling for a new and reformed MOC program.]
Q: What convinced ASH to expand its journals by adding Blood Neoplasia and Blood Vessels, Thrombosis & Hemostasis?
Dr. Robert A. Brodsky: ASH has two flagship journals right now, Blood and Blood Advances, and they’re both very competitive, high-impact journals. It turns out there’s not enough room to publish all the new science, and they end up rejecting the majority of the submissions that come to them. We decided to keep these journals in the ASH family because there’s some fantastic clinical trials and science that would be going elsewhere.
Dr. Brodsky’s sons both have medical degrees: Brett Brodsky, DO, is a resident at Virginia Commonwealth University who plans to become a sports medicine specialist, and Max Brodsky, MD, is a second-year fellow in hematology at Johns Hopkins University.
In an interview, Max Brodsky, MD, talked about the roots of his family’s dedication to caring for others.
Q: What drew you to hematology?
Dr. Max Brodsky: I’ve watched both my dad and my grandfather be leaders in the field as both physicians and scientists, and that was very inspirational for me to see. And I went to a medical school [Drexel University College of Medicine] that my dad went to and where my grandfather was on faculty. That was like walking in their footsteps in a major way.
Q: What do you hope to focus on as a hematologist?
Dr. Max Brodsky: I’m still working through that, but I am really interested in thrombotic thrombocytopenic purpura. Patients used to not be able to survive their initial episodes, but now we have good treatments and are able to follow them as outpatients. With this whole cohort of patients that are surviving, we’re seeing that they have more health problems — more heart disease, more strokes and kidney disease. There’s a whole growing field exploring how to treat these patients for their lifespan.
Q: How do you deal with the reality that more of your patients will die than in some other medical fields?
Dr. Max Brodsky: It is challenging, but I also see those moments as opportunities to support patients and families. I’m good at connecting to patients and families who are in scary situations. I’ve always had that skill of putting people at ease, making people feel calm, knowing that they can trust me, and I have their best interests in mind.
Q: Why do you think your family is so committed to medicine?
Dr. Max Brodsky: We’re Jewish, and looking to help the world is one of the main core values of Judaism. The Torah expects us to make this world better. Actually, my great-grandfather Max, whom I’m named after, used to dig tunnels to help people escape Ukraine and get to freedom. He was always looking to help others as well. My great-grandmother was shot crossing the border escaping from Ukraine, and he carried her the whole way to the boat. They lived in very poor West Philadelphia and poured everything into my grandfather. He became a great doctor, and his sons and his grandchildren are in medicine today.
*Correction, 12/11: A previous version of this story misstated the amount of ASH’s $19 million investment in developing fellowships with a focus on hematology.
In interviews, Robert and Max Brodsky spoke about the appeal of hematology and the threads that unite them with family members who came before. The elder Brodsky also talked about the work that’s made him the proudest during his year-long presidency at ASH.
Robert A. Brodsky is professor of medicine and director of hematology at Johns Hopkins University, Baltimore. He is stepping down as ASH president at its annual meeting in San Diego, December 9-12. Here are excerpts from our conversation:
Q: What drew your dad into medicine?
Dr. Robert A. Brodsky: He was going through his medical training at the University of Pennsylvania, then the Vietnam War came, and he served at the National Institutes of Health in what they referred to as the Yellow Berets. He got very interested in retroviruses and viruses that lead to cancer, which was a foreign idea at the time. This led him into hematology, stem cells, and myeloproliferative disorders.
He had a very successful career in hematology and just loved it. He performed the first bone marrow transplant in the tristate area of Pennsylvania, Delaware, and New Jersey.
Q: What did he like about hematology specifically?
Dr. Robert A. Brodsky: It’s a fascinating field, probably the most scientific area of medicine. It’s so easy to access blood and bone marrow. You can grow it, you can look at it, you can see it. It’s hard to do that with a lung, heart, kidney, or brain. Even back then, they could translate some of the science. What really drew him to hematology — and me, for that matter — was looking at a blood smear or bone marrow and being able to make a diagnosis. The other thing is the personal aspect. Hematologists tend to like the long-term relationships that they develop with their patients over the years.
Q: What were the biggest transformations in hematology during his career?
Dr. Robert A. Brodsky: Bone marrow transplant had the biggest impact, and it’s an area he really pioneered. He was very much involved in some of the early bone marrow transplants and was very close with Dr. George W. Santos, who was at Johns Hopkins and one of the big pioneers in that area as well. To be able to take marrow from related donors, get it to grow without the patient rejecting it, and cure a disease, was really huge. When he started doing this, patients had no other option. To see patients be cured was incredibly satisfying to him.
Q: How did you end up following your father into hematology?
Dr. Robert A. Brodsky: My brother Jeff, who’s a surgeon and older than me, knew he was going into medicine — probably about 3 hours after he was born. I came to it late. I was a political science major as an undergrad and really trying to figure out what I wanted to do. In my sophomore year, I decided I wanted to give this a shot. My dad worked very hard, long hours, but you could tell he loved what he did. And he was never absent, always involved in our lives and still made time for everyone. At some level, that must have had an influence on me.
Q: What has changed in hematology over your 30-plus years in medicine?
A: When I look back at when I was a fellow, it’s just mind-boggling how many lethal or life-threatening diseases are now pretty easy to treat. I studied disorders like aplastic anemia, which was very fatal. Without treatment, patients would die within a year. Now, over 95% are cured. Another classic examples is chronic myeloid leukemia disorder. Back when I was a fellow, the median survival for CML was maybe 4 to 6 years. Now, Kareem Abdul Jabbar has had this[for about 15 years]. Also a lot of hematologic malignancies are being cured with immunotherapy approaches. We’ve figured out the pathophysiology of a lot of diseases, and there are incredible genetic diagnostic assays.
Q: What was your father’s relationship with ASH?
Dr. Robert A. Brodsky: The first ASH meeting was 1958 in Atlantic City, New Jersey. There were 300 hematologists there, and my dad was one of them. We’re going to have over 30,000 people in San Diego, which is a record, and another 5,000 or 6,000 virtually.
Q: As ASH president, what are your biggest accomplishments when it comes to addressing the shortage of hematologists and other issues?
Dr. Robert A. Brodsky: ASH is investing $19 million to develop fellowships with a focus on hematology.* This is going to put lots of new hematologists into the workforce over the next 5 to 10 years. We’ve also been working on the Maintenance of Certification [MOC] process to make it less onerous on physicians. It’s really a bad process, and it’s not just ASH [that’s complaining], it’s all of medicine. We’re hearing this from GI, endocrine, renal and the general internists.
[In a September 2023 letter to the American Board of Internal Medicine’s president and chief officer, Dr. Brodsky wrote that “ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program.” ASH is calling for a new and reformed MOC program.]
Q: What convinced ASH to expand its journals by adding Blood Neoplasia and Blood Vessels, Thrombosis & Hemostasis?
Dr. Robert A. Brodsky: ASH has two flagship journals right now, Blood and Blood Advances, and they’re both very competitive, high-impact journals. It turns out there’s not enough room to publish all the new science, and they end up rejecting the majority of the submissions that come to them. We decided to keep these journals in the ASH family because there’s some fantastic clinical trials and science that would be going elsewhere.
Dr. Brodsky’s sons both have medical degrees: Brett Brodsky, DO, is a resident at Virginia Commonwealth University who plans to become a sports medicine specialist, and Max Brodsky, MD, is a second-year fellow in hematology at Johns Hopkins University.
In an interview, Max Brodsky, MD, talked about the roots of his family’s dedication to caring for others.
Q: What drew you to hematology?
Dr. Max Brodsky: I’ve watched both my dad and my grandfather be leaders in the field as both physicians and scientists, and that was very inspirational for me to see. And I went to a medical school [Drexel University College of Medicine] that my dad went to and where my grandfather was on faculty. That was like walking in their footsteps in a major way.
Q: What do you hope to focus on as a hematologist?
Dr. Max Brodsky: I’m still working through that, but I am really interested in thrombotic thrombocytopenic purpura. Patients used to not be able to survive their initial episodes, but now we have good treatments and are able to follow them as outpatients. With this whole cohort of patients that are surviving, we’re seeing that they have more health problems — more heart disease, more strokes and kidney disease. There’s a whole growing field exploring how to treat these patients for their lifespan.
Q: How do you deal with the reality that more of your patients will die than in some other medical fields?
Dr. Max Brodsky: It is challenging, but I also see those moments as opportunities to support patients and families. I’m good at connecting to patients and families who are in scary situations. I’ve always had that skill of putting people at ease, making people feel calm, knowing that they can trust me, and I have their best interests in mind.
Q: Why do you think your family is so committed to medicine?
Dr. Max Brodsky: We’re Jewish, and looking to help the world is one of the main core values of Judaism. The Torah expects us to make this world better. Actually, my great-grandfather Max, whom I’m named after, used to dig tunnels to help people escape Ukraine and get to freedom. He was always looking to help others as well. My great-grandmother was shot crossing the border escaping from Ukraine, and he carried her the whole way to the boat. They lived in very poor West Philadelphia and poured everything into my grandfather. He became a great doctor, and his sons and his grandchildren are in medicine today.
*Correction, 12/11: A previous version of this story misstated the amount of ASH’s $19 million investment in developing fellowships with a focus on hematology.
FROM ASH 2023
ASH 2023: Equity, Sickle Cell, and Real-Life Outcomes
Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute and secretary of ASH, added that insight into actual patient experiences also will be a major theme at ASH 2023.
“There is a huge growth in research on outcomes and focusing on using real-world data and how important that is,” Dr. Dunbar said. “Academic research and hematology is really focusing on patient-reported outcomes and how care is delivered in a real-world setting – actually looking at what matters to patients. Are they alive in a certain number of years? And how are they feeling?”
As an example, Dr. Dunbar pointed to an abstract that examined clinical databases in Canada and found that real-world outcomes in multiple myeloma treatments were much worse than those in the original clinical trials for the therapies. Patients reached relapse 44% faster and their overall survival was 75% worse.
In the media briefing, ASH chair of communications Mikkael A. Sekeres, MD, MS, of the Sylvester Comprehensive Cancer Center at the University of Miami, noted that patients in these types of clinical trials “are just these pristine specimens of human beings except for the cancer that’s being treated.”
Dr. Dunbar agreed, noting that “patients who are able to enroll in clinical trials are more likely to be able to show up at the treatment center at the right time and for every dose, have transportation, and afford drugs to prevent side effects. They might stay on the drug for longer, or they have nurses who are always encouraging them of how to make it through a toxicity.”
Hematologists and patients should consider randomized controlled trials to be “the best possible outcome, and perhaps adjust their thinking if an individual patient is older, sicker, or less able to follow a regimen exactly,” she said.
Another highlighted study linked worse outcomes in African-Americans with pediatric acute myeloid leukemia to genetic traits that are more common in that population. The traits “likely explain at least in part the worst outcomes in Black patients in prior studies and on some regimens,” Dr. Dunbar said.
She added that the findings emphasize how testing for genetic variants and biomarkers that impact outcomes should be performed “instead of assuming that a certain dose should be given simply based on perceived or reported race or ethnicity.”
ASH President Robert A. Brodsky, MD, of Johns Hopkins University School of Medicine, Baltimore, highlighted an abstract that reported on the use of AI as a clinical decision support tool to differentiate two easily confused conditions — prefibrotic primary myelofibrosis and essential thrombocythemia.
AI “is a tool that’s going to help pathologists make more accurate and faster diagnoses,” he said. He also spotlighted an abstract about the use of “social media listening” to understand the experiences of patients with SCD and their caregivers. “There can be a lot of misuse and waste of time with social media, but they used this in a way to try and gain insight as to what’s really important to the patients and the caregiver.”
Also, in regard to SCD, Dr. Dunbar pointed to a study that reports on outcomes in patients who received lovotibeglogene autotemcel (lovo-cel) gene therapy for up to 60 months. Both this treatment and a CRISPR-based therapy called exa-cel “appear to result in comparable very impressive efficacy in terms of pain crises and organ dysfunction,” she said. “The hurdle is going to be figuring out how to deliver what will be very expensive and complicated therapies — but likely curative — therapies to patients.”
Another study to be presented at ASH — coauthored by Dr. Brodsky — shows promising results from reduced-intensity haploidentical bone marrow transplantation in adults with severe SCD. Results were similar to those seen with bone marrow from matched siblings, Dr. Sekeres said.
He added that more clarity is needed about new treatment options for SCD, perhaps through a “randomized trial where patients upfront get a haploidentical bone marrow transplant or fully matched bone marrow transplant. Then other patients are randomized to some of these other, newer technology therapies, and we follow them over time. We’re looking not only for overall survival but complications of the therapy itself and how many patients relapse from the treatment.”
Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute and secretary of ASH, added that insight into actual patient experiences also will be a major theme at ASH 2023.
“There is a huge growth in research on outcomes and focusing on using real-world data and how important that is,” Dr. Dunbar said. “Academic research and hematology is really focusing on patient-reported outcomes and how care is delivered in a real-world setting – actually looking at what matters to patients. Are they alive in a certain number of years? And how are they feeling?”
As an example, Dr. Dunbar pointed to an abstract that examined clinical databases in Canada and found that real-world outcomes in multiple myeloma treatments were much worse than those in the original clinical trials for the therapies. Patients reached relapse 44% faster and their overall survival was 75% worse.
In the media briefing, ASH chair of communications Mikkael A. Sekeres, MD, MS, of the Sylvester Comprehensive Cancer Center at the University of Miami, noted that patients in these types of clinical trials “are just these pristine specimens of human beings except for the cancer that’s being treated.”
Dr. Dunbar agreed, noting that “patients who are able to enroll in clinical trials are more likely to be able to show up at the treatment center at the right time and for every dose, have transportation, and afford drugs to prevent side effects. They might stay on the drug for longer, or they have nurses who are always encouraging them of how to make it through a toxicity.”
Hematologists and patients should consider randomized controlled trials to be “the best possible outcome, and perhaps adjust their thinking if an individual patient is older, sicker, or less able to follow a regimen exactly,” she said.
Another highlighted study linked worse outcomes in African-Americans with pediatric acute myeloid leukemia to genetic traits that are more common in that population. The traits “likely explain at least in part the worst outcomes in Black patients in prior studies and on some regimens,” Dr. Dunbar said.
She added that the findings emphasize how testing for genetic variants and biomarkers that impact outcomes should be performed “instead of assuming that a certain dose should be given simply based on perceived or reported race or ethnicity.”
ASH President Robert A. Brodsky, MD, of Johns Hopkins University School of Medicine, Baltimore, highlighted an abstract that reported on the use of AI as a clinical decision support tool to differentiate two easily confused conditions — prefibrotic primary myelofibrosis and essential thrombocythemia.
AI “is a tool that’s going to help pathologists make more accurate and faster diagnoses,” he said. He also spotlighted an abstract about the use of “social media listening” to understand the experiences of patients with SCD and their caregivers. “There can be a lot of misuse and waste of time with social media, but they used this in a way to try and gain insight as to what’s really important to the patients and the caregiver.”
Also, in regard to SCD, Dr. Dunbar pointed to a study that reports on outcomes in patients who received lovotibeglogene autotemcel (lovo-cel) gene therapy for up to 60 months. Both this treatment and a CRISPR-based therapy called exa-cel “appear to result in comparable very impressive efficacy in terms of pain crises and organ dysfunction,” she said. “The hurdle is going to be figuring out how to deliver what will be very expensive and complicated therapies — but likely curative — therapies to patients.”
Another study to be presented at ASH — coauthored by Dr. Brodsky — shows promising results from reduced-intensity haploidentical bone marrow transplantation in adults with severe SCD. Results were similar to those seen with bone marrow from matched siblings, Dr. Sekeres said.
He added that more clarity is needed about new treatment options for SCD, perhaps through a “randomized trial where patients upfront get a haploidentical bone marrow transplant or fully matched bone marrow transplant. Then other patients are randomized to some of these other, newer technology therapies, and we follow them over time. We’re looking not only for overall survival but complications of the therapy itself and how many patients relapse from the treatment.”
Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute and secretary of ASH, added that insight into actual patient experiences also will be a major theme at ASH 2023.
“There is a huge growth in research on outcomes and focusing on using real-world data and how important that is,” Dr. Dunbar said. “Academic research and hematology is really focusing on patient-reported outcomes and how care is delivered in a real-world setting – actually looking at what matters to patients. Are they alive in a certain number of years? And how are they feeling?”
As an example, Dr. Dunbar pointed to an abstract that examined clinical databases in Canada and found that real-world outcomes in multiple myeloma treatments were much worse than those in the original clinical trials for the therapies. Patients reached relapse 44% faster and their overall survival was 75% worse.
In the media briefing, ASH chair of communications Mikkael A. Sekeres, MD, MS, of the Sylvester Comprehensive Cancer Center at the University of Miami, noted that patients in these types of clinical trials “are just these pristine specimens of human beings except for the cancer that’s being treated.”
Dr. Dunbar agreed, noting that “patients who are able to enroll in clinical trials are more likely to be able to show up at the treatment center at the right time and for every dose, have transportation, and afford drugs to prevent side effects. They might stay on the drug for longer, or they have nurses who are always encouraging them of how to make it through a toxicity.”
Hematologists and patients should consider randomized controlled trials to be “the best possible outcome, and perhaps adjust their thinking if an individual patient is older, sicker, or less able to follow a regimen exactly,” she said.
Another highlighted study linked worse outcomes in African-Americans with pediatric acute myeloid leukemia to genetic traits that are more common in that population. The traits “likely explain at least in part the worst outcomes in Black patients in prior studies and on some regimens,” Dr. Dunbar said.
She added that the findings emphasize how testing for genetic variants and biomarkers that impact outcomes should be performed “instead of assuming that a certain dose should be given simply based on perceived or reported race or ethnicity.”
ASH President Robert A. Brodsky, MD, of Johns Hopkins University School of Medicine, Baltimore, highlighted an abstract that reported on the use of AI as a clinical decision support tool to differentiate two easily confused conditions — prefibrotic primary myelofibrosis and essential thrombocythemia.
AI “is a tool that’s going to help pathologists make more accurate and faster diagnoses,” he said. He also spotlighted an abstract about the use of “social media listening” to understand the experiences of patients with SCD and their caregivers. “There can be a lot of misuse and waste of time with social media, but they used this in a way to try and gain insight as to what’s really important to the patients and the caregiver.”
Also, in regard to SCD, Dr. Dunbar pointed to a study that reports on outcomes in patients who received lovotibeglogene autotemcel (lovo-cel) gene therapy for up to 60 months. Both this treatment and a CRISPR-based therapy called exa-cel “appear to result in comparable very impressive efficacy in terms of pain crises and organ dysfunction,” she said. “The hurdle is going to be figuring out how to deliver what will be very expensive and complicated therapies — but likely curative — therapies to patients.”
Another study to be presented at ASH — coauthored by Dr. Brodsky — shows promising results from reduced-intensity haploidentical bone marrow transplantation in adults with severe SCD. Results were similar to those seen with bone marrow from matched siblings, Dr. Sekeres said.
He added that more clarity is needed about new treatment options for SCD, perhaps through a “randomized trial where patients upfront get a haploidentical bone marrow transplant or fully matched bone marrow transplant. Then other patients are randomized to some of these other, newer technology therapies, and we follow them over time. We’re looking not only for overall survival but complications of the therapy itself and how many patients relapse from the treatment.”
AT ASH 2023
FDA OKs new agent to block chemotherapy-induced neutropenia
Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.
The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.
The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.
The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.
During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.
The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.
The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.
A version of this article first appeared on Medscape.com.
Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.
The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.
The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.
The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.
During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.
The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.
The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.
A version of this article first appeared on Medscape.com.
Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.
The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.
The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.
The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.
During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.
The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.
The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.
A version of this article first appeared on Medscape.com.
Study confirms small blood cancer risk from CT scans
The findings, published online in Nature Medicine, are based on more than 1.3 million CT scans in nearly 900,000 people younger than 22 years old when scanned.
This study makes a “significant contribution to the understanding of the effects of ionizing radiation, specifically x-rays, on the human body at the levels of radiation exposure encountered in diagnostic CT procedures,” Peter Marsden, PhD, and Jim Thurston, radiation protection experts at Dorset County (England) Hospital, NHS Foundation Trust, said in a press release from the U.K. nonprofit Science Media Centre.
These findings highlight levels of risk that “align with those currently estimated and do not suggest that the use of CT carries a greater risk than previously thought,” Dr. Marsden and Thurston said.
Exposure to moderate- (≥ 100 mGy) to high-dose (≥ 1 Gy) ionizing radiation is a well-established risk factor for leukemia in both children and adults. However, the risk associated with low-dose exposure (< 100 mGy) typically associated with diagnostic CT exams in children and teens remains unclear.
The current study, coordinated by the International Agency for Research on Cancer, aimed to improve direct estimates of cancer risk from low-dose radiation exposure from CT scans performed in childhood and adolescence. The researchers estimated radiation doses to the active bone marrow based on body part scanned, patient characteristics, time period, and inferred CT technical parameters.
A total of 790 hematologic malignancies, including lymphoid and myeloid malignancies, were identified during follow-up. More than half (51%) of the cases were diagnosed in people under age 20 and 88.5% were diagnosed in people under age 30 years.
Overall, the observational study found a nearly twofold excess risk of all hematologic malignancies per 100 mGy in children, adolescents, and young adults, with similar risk estimates observed for lymphoid and myeloid cancers. The excess relative risk for hematologic malignancies increased as the number of CT exams increased – with risk rising by 43% per exam.
The results of this study “strengthen the findings from previous low-dose studies of a consistent and robust dose-related increased risk of radiation-induced hematological malignancies” and highlight the importance of optimizing doses in this patient population, study author Elisabeth Cardis, PhD, with the Barcelona Institute for Global Health, and colleagues concluded.
Sarah McQuaid, PhD, chair of the nuclear medicine special interest group, Institute of Physics and Engineering in Medicine, York, England, agreed.
“This publication indicates that there could be a small cancer risk from CT scans in young people, but it is important for this to be viewed in the context of the substantial benefit these scans bring, due to the important diagnostic information they provide,” Dr. McQuaid said in the press release. Overall, “the number of patients whose medical care will have been improved from these CT scans will have been very high, and lives undoubtedly saved as a result.”
The study had no commercial funding. The authors and outside experts reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The findings, published online in Nature Medicine, are based on more than 1.3 million CT scans in nearly 900,000 people younger than 22 years old when scanned.
This study makes a “significant contribution to the understanding of the effects of ionizing radiation, specifically x-rays, on the human body at the levels of radiation exposure encountered in diagnostic CT procedures,” Peter Marsden, PhD, and Jim Thurston, radiation protection experts at Dorset County (England) Hospital, NHS Foundation Trust, said in a press release from the U.K. nonprofit Science Media Centre.
These findings highlight levels of risk that “align with those currently estimated and do not suggest that the use of CT carries a greater risk than previously thought,” Dr. Marsden and Thurston said.
Exposure to moderate- (≥ 100 mGy) to high-dose (≥ 1 Gy) ionizing radiation is a well-established risk factor for leukemia in both children and adults. However, the risk associated with low-dose exposure (< 100 mGy) typically associated with diagnostic CT exams in children and teens remains unclear.
The current study, coordinated by the International Agency for Research on Cancer, aimed to improve direct estimates of cancer risk from low-dose radiation exposure from CT scans performed in childhood and adolescence. The researchers estimated radiation doses to the active bone marrow based on body part scanned, patient characteristics, time period, and inferred CT technical parameters.
A total of 790 hematologic malignancies, including lymphoid and myeloid malignancies, were identified during follow-up. More than half (51%) of the cases were diagnosed in people under age 20 and 88.5% were diagnosed in people under age 30 years.
Overall, the observational study found a nearly twofold excess risk of all hematologic malignancies per 100 mGy in children, adolescents, and young adults, with similar risk estimates observed for lymphoid and myeloid cancers. The excess relative risk for hematologic malignancies increased as the number of CT exams increased – with risk rising by 43% per exam.
The results of this study “strengthen the findings from previous low-dose studies of a consistent and robust dose-related increased risk of radiation-induced hematological malignancies” and highlight the importance of optimizing doses in this patient population, study author Elisabeth Cardis, PhD, with the Barcelona Institute for Global Health, and colleagues concluded.
Sarah McQuaid, PhD, chair of the nuclear medicine special interest group, Institute of Physics and Engineering in Medicine, York, England, agreed.
“This publication indicates that there could be a small cancer risk from CT scans in young people, but it is important for this to be viewed in the context of the substantial benefit these scans bring, due to the important diagnostic information they provide,” Dr. McQuaid said in the press release. Overall, “the number of patients whose medical care will have been improved from these CT scans will have been very high, and lives undoubtedly saved as a result.”
The study had no commercial funding. The authors and outside experts reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The findings, published online in Nature Medicine, are based on more than 1.3 million CT scans in nearly 900,000 people younger than 22 years old when scanned.
This study makes a “significant contribution to the understanding of the effects of ionizing radiation, specifically x-rays, on the human body at the levels of radiation exposure encountered in diagnostic CT procedures,” Peter Marsden, PhD, and Jim Thurston, radiation protection experts at Dorset County (England) Hospital, NHS Foundation Trust, said in a press release from the U.K. nonprofit Science Media Centre.
These findings highlight levels of risk that “align with those currently estimated and do not suggest that the use of CT carries a greater risk than previously thought,” Dr. Marsden and Thurston said.
Exposure to moderate- (≥ 100 mGy) to high-dose (≥ 1 Gy) ionizing radiation is a well-established risk factor for leukemia in both children and adults. However, the risk associated with low-dose exposure (< 100 mGy) typically associated with diagnostic CT exams in children and teens remains unclear.
The current study, coordinated by the International Agency for Research on Cancer, aimed to improve direct estimates of cancer risk from low-dose radiation exposure from CT scans performed in childhood and adolescence. The researchers estimated radiation doses to the active bone marrow based on body part scanned, patient characteristics, time period, and inferred CT technical parameters.
A total of 790 hematologic malignancies, including lymphoid and myeloid malignancies, were identified during follow-up. More than half (51%) of the cases were diagnosed in people under age 20 and 88.5% were diagnosed in people under age 30 years.
Overall, the observational study found a nearly twofold excess risk of all hematologic malignancies per 100 mGy in children, adolescents, and young adults, with similar risk estimates observed for lymphoid and myeloid cancers. The excess relative risk for hematologic malignancies increased as the number of CT exams increased – with risk rising by 43% per exam.
The results of this study “strengthen the findings from previous low-dose studies of a consistent and robust dose-related increased risk of radiation-induced hematological malignancies” and highlight the importance of optimizing doses in this patient population, study author Elisabeth Cardis, PhD, with the Barcelona Institute for Global Health, and colleagues concluded.
Sarah McQuaid, PhD, chair of the nuclear medicine special interest group, Institute of Physics and Engineering in Medicine, York, England, agreed.
“This publication indicates that there could be a small cancer risk from CT scans in young people, but it is important for this to be viewed in the context of the substantial benefit these scans bring, due to the important diagnostic information they provide,” Dr. McQuaid said in the press release. Overall, “the number of patients whose medical care will have been improved from these CT scans will have been very high, and lives undoubtedly saved as a result.”
The study had no commercial funding. The authors and outside experts reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NATURE MEDICINE
FDA OKs ivosidenib for IDH1-mutated myelodysplastic syndromes
The agency also approved the Abbott RealTime IDH1 Assay to test for the mutation.
Almost 4% of the 16,000 people diagnosed with MDS in the United States each year carry an isocitrate dehydrogenase-1 (IDH1) mutation, which increases their risk for poor outcomes, such as transformation to acute myeloid leukemia, Servier explained in a press announcement.
Ivosidenib is an IDH1 inhibitor that has previously been approved for IDH1-mutated AML and locally advanced or metastatic cholangiocarcinoma. The new approval makes it the only targeted therapy approved for relapsed or refractory MDS with the mutation, Servier said.
The FDA approval was based on a phase 1 study in 18 adults aged 61-82 years with IDH1-mutated relapsed or refractory MDS. Patients started at a dose of 500 mg daily in 28-day cycles until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation. Median treatment duration was 9.3 months, and one patient went on to receive a transplant.
Overall survival was a median of 35.7 months. Fifteen patients (83.3%) had an objective response and 7 (38.9%) went into complete remission after a median of 1.9 months of treatment. The median duration of remission had not been reached at data cutoff.
Among the 9 patients dependent on RBC or platelet transfusions at baseline, 6 (66.7%) no longer needed them during any 56-day post-baseline period.
Grade 3/4 adverse events in 5% or more of patients included arthralgia, hypertension, fatigue, mucositis, and leukocytosis.
Labeling carries a boxed warning of potentially fatal differentiation syndrome. Ivosidenib can also cause QTc prolongation.
A version of this article first appeared on Medscape.com.
The agency also approved the Abbott RealTime IDH1 Assay to test for the mutation.
Almost 4% of the 16,000 people diagnosed with MDS in the United States each year carry an isocitrate dehydrogenase-1 (IDH1) mutation, which increases their risk for poor outcomes, such as transformation to acute myeloid leukemia, Servier explained in a press announcement.
Ivosidenib is an IDH1 inhibitor that has previously been approved for IDH1-mutated AML and locally advanced or metastatic cholangiocarcinoma. The new approval makes it the only targeted therapy approved for relapsed or refractory MDS with the mutation, Servier said.
The FDA approval was based on a phase 1 study in 18 adults aged 61-82 years with IDH1-mutated relapsed or refractory MDS. Patients started at a dose of 500 mg daily in 28-day cycles until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation. Median treatment duration was 9.3 months, and one patient went on to receive a transplant.
Overall survival was a median of 35.7 months. Fifteen patients (83.3%) had an objective response and 7 (38.9%) went into complete remission after a median of 1.9 months of treatment. The median duration of remission had not been reached at data cutoff.
Among the 9 patients dependent on RBC or platelet transfusions at baseline, 6 (66.7%) no longer needed them during any 56-day post-baseline period.
Grade 3/4 adverse events in 5% or more of patients included arthralgia, hypertension, fatigue, mucositis, and leukocytosis.
Labeling carries a boxed warning of potentially fatal differentiation syndrome. Ivosidenib can also cause QTc prolongation.
A version of this article first appeared on Medscape.com.
The agency also approved the Abbott RealTime IDH1 Assay to test for the mutation.
Almost 4% of the 16,000 people diagnosed with MDS in the United States each year carry an isocitrate dehydrogenase-1 (IDH1) mutation, which increases their risk for poor outcomes, such as transformation to acute myeloid leukemia, Servier explained in a press announcement.
Ivosidenib is an IDH1 inhibitor that has previously been approved for IDH1-mutated AML and locally advanced or metastatic cholangiocarcinoma. The new approval makes it the only targeted therapy approved for relapsed or refractory MDS with the mutation, Servier said.
The FDA approval was based on a phase 1 study in 18 adults aged 61-82 years with IDH1-mutated relapsed or refractory MDS. Patients started at a dose of 500 mg daily in 28-day cycles until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation. Median treatment duration was 9.3 months, and one patient went on to receive a transplant.
Overall survival was a median of 35.7 months. Fifteen patients (83.3%) had an objective response and 7 (38.9%) went into complete remission after a median of 1.9 months of treatment. The median duration of remission had not been reached at data cutoff.
Among the 9 patients dependent on RBC or platelet transfusions at baseline, 6 (66.7%) no longer needed them during any 56-day post-baseline period.
Grade 3/4 adverse events in 5% or more of patients included arthralgia, hypertension, fatigue, mucositis, and leukocytosis.
Labeling carries a boxed warning of potentially fatal differentiation syndrome. Ivosidenib can also cause QTc prolongation.
A version of this article first appeared on Medscape.com.
Using JAK inhibitors for myelofibrosis
“We are thankfully starting to be blessed with more options than we’ve ever had,” he said, but “in the front-line proliferative setting, ruxolitinib has remained the standard of care.” It’s “well established in higher-risk patients and very much an option for very symptomatic lower-risk patients.”
Dr. Hunter helped his colleagues navigate the evolving field of JAK inhibition for myelofibrosis in a presentation titled “Choosing and Properly Using a JAK Inhibitor in Myelofibrosis,”at the Society of Hematologic Oncology annual meeting.
Ruxolitinib was the first JAK inhibitor for myelofibrosis on the U.S. market, approved in 2011. Two more have followed, fedratinib in 2019 and pacritinib in 2022.
A fourth JAK inhibitor for myelofibrosis, momelotinib, is under Food and Drug Administration review with a decision expected shortly.
JAK inhibitors disrupt a key pathogenic pathway in myelofibrosis and are a mainstay of treatment, but Dr. Hunter noted that they should not replace allogeneic transplants in patients who are candidates because transplants remain “the best way to achieve long term survival, especially in higher risk patients.”
He noted that not every patient needs a JAK inhibitor, especially “lower-risk, more asymptomatic patients who are predominantly manifesting with cytopenias. [They] are less likely to benefit.”
Dr. Hunter said that although ruxolitinib remains a treatment of choice, fedratinib “is certainly an option” with comparable rates of symptom control and splenomegaly reduction. Also, while ruxolitinib is dosed according to platelet levels, fedratinib allows for full dosing down to a platelet count of 50 x 109/L.
“But there’s more GI toxicity than with ruxolitinib, especially in the first couple of months,” he said, as well as a black box warning of Wernicke’s encephalopathy. “I generally put all my [fedratinib] patients on thiamine repletion as a precaution.”
One of the most challenging aspects of using JAK inhibitors for myelofibrosis is their tendency to cause cytopenia, particularly anemia and thrombocytopenia, which, ironically, are also hallmarks of myelofibrosis itself.
Although there’s an alternative low-dose ruxolitinib regimen that can be effective in anemic settings, the approval of pacritinib and most likely momelotinib is particularly helpful for cytopenic patients, “a population which historically has been very hard to treat with our prior agents,” Dr. Hunter said.
Pacritinib is approved specifically for patients with platelet counts below 50 x 109/L; momelotinib also included lower platelet counts in several studies. Both agents indirectly boost erythropoiesis with subsequent amelioration of anemia.
“Momelotinib is an important emerging agent for these more anemic patients,” with a spleen response comparable to ruxolitinib and significantly higher rates of transfusion independence, but with lower rates of symptom control, Dr. Hunter said.
Pacritinib “really helps extend the benefit of JAK inhibitors to a group of thrombocytopenic patients who have been hard to treat with ruxolitinib,” with the added potential of improving anemia, although, like fedratinib, it has more GI toxicity, he said.
There are multiple add-on options for JAK inhibitor patients with anemia, including luspatercept, an erythropoiesis-stimulating agent approved for anemia in patients with myelodysplastic syndromes; promising results were reported recently for myelofibrosis.
Fedratinib, pacritinib, and momelotinib all have activity in the second line after ruxolitinib failure, Dr. Hunter noted, but he cautioned that ruxolitinib must be tapered over a few weeks, not stopped abruptly, to avoid withdrawal symptoms. Some clinicians overlap JAK inhibitors a day or two to avoid issues.
“Clinical trials should still be considered in many of these settings,” he said, adding that emerging agents are under development, including multiple combination therapies, often with JAK inhibitors as the background.
No disclosure information was reported.
“We are thankfully starting to be blessed with more options than we’ve ever had,” he said, but “in the front-line proliferative setting, ruxolitinib has remained the standard of care.” It’s “well established in higher-risk patients and very much an option for very symptomatic lower-risk patients.”
Dr. Hunter helped his colleagues navigate the evolving field of JAK inhibition for myelofibrosis in a presentation titled “Choosing and Properly Using a JAK Inhibitor in Myelofibrosis,”at the Society of Hematologic Oncology annual meeting.
Ruxolitinib was the first JAK inhibitor for myelofibrosis on the U.S. market, approved in 2011. Two more have followed, fedratinib in 2019 and pacritinib in 2022.
A fourth JAK inhibitor for myelofibrosis, momelotinib, is under Food and Drug Administration review with a decision expected shortly.
JAK inhibitors disrupt a key pathogenic pathway in myelofibrosis and are a mainstay of treatment, but Dr. Hunter noted that they should not replace allogeneic transplants in patients who are candidates because transplants remain “the best way to achieve long term survival, especially in higher risk patients.”
He noted that not every patient needs a JAK inhibitor, especially “lower-risk, more asymptomatic patients who are predominantly manifesting with cytopenias. [They] are less likely to benefit.”
Dr. Hunter said that although ruxolitinib remains a treatment of choice, fedratinib “is certainly an option” with comparable rates of symptom control and splenomegaly reduction. Also, while ruxolitinib is dosed according to platelet levels, fedratinib allows for full dosing down to a platelet count of 50 x 109/L.
“But there’s more GI toxicity than with ruxolitinib, especially in the first couple of months,” he said, as well as a black box warning of Wernicke’s encephalopathy. “I generally put all my [fedratinib] patients on thiamine repletion as a precaution.”
One of the most challenging aspects of using JAK inhibitors for myelofibrosis is their tendency to cause cytopenia, particularly anemia and thrombocytopenia, which, ironically, are also hallmarks of myelofibrosis itself.
Although there’s an alternative low-dose ruxolitinib regimen that can be effective in anemic settings, the approval of pacritinib and most likely momelotinib is particularly helpful for cytopenic patients, “a population which historically has been very hard to treat with our prior agents,” Dr. Hunter said.
Pacritinib is approved specifically for patients with platelet counts below 50 x 109/L; momelotinib also included lower platelet counts in several studies. Both agents indirectly boost erythropoiesis with subsequent amelioration of anemia.
“Momelotinib is an important emerging agent for these more anemic patients,” with a spleen response comparable to ruxolitinib and significantly higher rates of transfusion independence, but with lower rates of symptom control, Dr. Hunter said.
Pacritinib “really helps extend the benefit of JAK inhibitors to a group of thrombocytopenic patients who have been hard to treat with ruxolitinib,” with the added potential of improving anemia, although, like fedratinib, it has more GI toxicity, he said.
There are multiple add-on options for JAK inhibitor patients with anemia, including luspatercept, an erythropoiesis-stimulating agent approved for anemia in patients with myelodysplastic syndromes; promising results were reported recently for myelofibrosis.
Fedratinib, pacritinib, and momelotinib all have activity in the second line after ruxolitinib failure, Dr. Hunter noted, but he cautioned that ruxolitinib must be tapered over a few weeks, not stopped abruptly, to avoid withdrawal symptoms. Some clinicians overlap JAK inhibitors a day or two to avoid issues.
“Clinical trials should still be considered in many of these settings,” he said, adding that emerging agents are under development, including multiple combination therapies, often with JAK inhibitors as the background.
No disclosure information was reported.
“We are thankfully starting to be blessed with more options than we’ve ever had,” he said, but “in the front-line proliferative setting, ruxolitinib has remained the standard of care.” It’s “well established in higher-risk patients and very much an option for very symptomatic lower-risk patients.”
Dr. Hunter helped his colleagues navigate the evolving field of JAK inhibition for myelofibrosis in a presentation titled “Choosing and Properly Using a JAK Inhibitor in Myelofibrosis,”at the Society of Hematologic Oncology annual meeting.
Ruxolitinib was the first JAK inhibitor for myelofibrosis on the U.S. market, approved in 2011. Two more have followed, fedratinib in 2019 and pacritinib in 2022.
A fourth JAK inhibitor for myelofibrosis, momelotinib, is under Food and Drug Administration review with a decision expected shortly.
JAK inhibitors disrupt a key pathogenic pathway in myelofibrosis and are a mainstay of treatment, but Dr. Hunter noted that they should not replace allogeneic transplants in patients who are candidates because transplants remain “the best way to achieve long term survival, especially in higher risk patients.”
He noted that not every patient needs a JAK inhibitor, especially “lower-risk, more asymptomatic patients who are predominantly manifesting with cytopenias. [They] are less likely to benefit.”
Dr. Hunter said that although ruxolitinib remains a treatment of choice, fedratinib “is certainly an option” with comparable rates of symptom control and splenomegaly reduction. Also, while ruxolitinib is dosed according to platelet levels, fedratinib allows for full dosing down to a platelet count of 50 x 109/L.
“But there’s more GI toxicity than with ruxolitinib, especially in the first couple of months,” he said, as well as a black box warning of Wernicke’s encephalopathy. “I generally put all my [fedratinib] patients on thiamine repletion as a precaution.”
One of the most challenging aspects of using JAK inhibitors for myelofibrosis is their tendency to cause cytopenia, particularly anemia and thrombocytopenia, which, ironically, are also hallmarks of myelofibrosis itself.
Although there’s an alternative low-dose ruxolitinib regimen that can be effective in anemic settings, the approval of pacritinib and most likely momelotinib is particularly helpful for cytopenic patients, “a population which historically has been very hard to treat with our prior agents,” Dr. Hunter said.
Pacritinib is approved specifically for patients with platelet counts below 50 x 109/L; momelotinib also included lower platelet counts in several studies. Both agents indirectly boost erythropoiesis with subsequent amelioration of anemia.
“Momelotinib is an important emerging agent for these more anemic patients,” with a spleen response comparable to ruxolitinib and significantly higher rates of transfusion independence, but with lower rates of symptom control, Dr. Hunter said.
Pacritinib “really helps extend the benefit of JAK inhibitors to a group of thrombocytopenic patients who have been hard to treat with ruxolitinib,” with the added potential of improving anemia, although, like fedratinib, it has more GI toxicity, he said.
There are multiple add-on options for JAK inhibitor patients with anemia, including luspatercept, an erythropoiesis-stimulating agent approved for anemia in patients with myelodysplastic syndromes; promising results were reported recently for myelofibrosis.
Fedratinib, pacritinib, and momelotinib all have activity in the second line after ruxolitinib failure, Dr. Hunter noted, but he cautioned that ruxolitinib must be tapered over a few weeks, not stopped abruptly, to avoid withdrawal symptoms. Some clinicians overlap JAK inhibitors a day or two to avoid issues.
“Clinical trials should still be considered in many of these settings,” he said, adding that emerging agents are under development, including multiple combination therapies, often with JAK inhibitors as the background.
No disclosure information was reported.
FROM SOHO 2023
CHP/CCUS: Low blood cancer risk for most patients
The reason is that patients will inevitably “go online and see that [the conditions are] associated with lots of bad things; it can really cause patients psychosocial harm if there is no one to explain what their risk is and also provide risk-specific management,” Dr. Weeks said at the annual meeting of the Society of Hematologic Oncology in Houston.
CHIP and CCUS are precursors of myeloid malignancies but for most patients, the risk of progression is less than 1%. CHIPS and CCUS are also associated with cardiovascular, rheumatologic, hepatic, and other diseases.
CHIP is defined by somatic mutations in myeloid malignancy driver genes with a variant allele fraction of 2% or more; CCUS is when those molecular features are accompanied by an unexplained and persistent anemia, thrombocytopenia, or neutropenia.
A small 2017 study suggested that about a third of patients with otherwise unexplained cytopenias have CCUS.
With the increasing use of next generation sequencing for tissue and liquid biopsies and other uses, the incidental diagnosis of both conditions is increasing.
Fortunately, Dr. Weeks’ group recently published a tool for predicting the risk of progression to myeloid malignancy.
Their “clonal hematopoiesis risk score” (CHRS) was developed and validated in over 400,000 healthy volunteers in the UK Biobank, with additional validation in cohorts from Dana Farber and the University of Pavia, Italy.
The CHRS incorporates eight high-risk genetic and clinical prognostic factors, including the type and number of genetic mutations in blood cells, factors related to red blood cell volume, and age over 65. It’s available online.
“You just input the patient’s information and it spits out if the patient is low, intermediate, or high risk for progression to any myeloid malignancy,” Dr. Weeks told her audience.
High-risk patients have about a 50% 10-year cumulative incidence of myeloid malignancy. The large majority of patients are low risk, however, and have a 10-year cumulative incidence of less than 1%. Patients in the middle have a 10-year risk of about 8%.
The low-risk group “is the population of people who probably don’t need to see a specialist,” and can be followed with an annual CBC with their primary care doctors plus further workup with any clinical change. Patients should also be evaluated for cardiovascular and other comorbidity risks.
“It’s the high-risk group we worry most about,” Dr. Weeks said. “We see them more often and repeat the next-generation sequencing” annually with a CBC at least every 6 months and a bone marrow biopsy with any clinical change.
“This is the population we would shuttle towards a clinical trial, as this is the population most likely to benefit,” she said.
The overarching goal of the several ongoing studies in CHIP/CCUS is to find a way to prevent progression to blood cancer. They range from prospective cohorts and single arm pilot studies to randomized clinical trials. One trial is evaluating canakinumab to prevent progression. “Intervention in clonal hematopoiesis might have the dual benefit of both preventing hematologic malignancy as well as reducing [the] inflammatory comorbidities,” Dr. Weeks said.
The reason is that patients will inevitably “go online and see that [the conditions are] associated with lots of bad things; it can really cause patients psychosocial harm if there is no one to explain what their risk is and also provide risk-specific management,” Dr. Weeks said at the annual meeting of the Society of Hematologic Oncology in Houston.
CHIP and CCUS are precursors of myeloid malignancies but for most patients, the risk of progression is less than 1%. CHIPS and CCUS are also associated with cardiovascular, rheumatologic, hepatic, and other diseases.
CHIP is defined by somatic mutations in myeloid malignancy driver genes with a variant allele fraction of 2% or more; CCUS is when those molecular features are accompanied by an unexplained and persistent anemia, thrombocytopenia, or neutropenia.
A small 2017 study suggested that about a third of patients with otherwise unexplained cytopenias have CCUS.
With the increasing use of next generation sequencing for tissue and liquid biopsies and other uses, the incidental diagnosis of both conditions is increasing.
Fortunately, Dr. Weeks’ group recently published a tool for predicting the risk of progression to myeloid malignancy.
Their “clonal hematopoiesis risk score” (CHRS) was developed and validated in over 400,000 healthy volunteers in the UK Biobank, with additional validation in cohorts from Dana Farber and the University of Pavia, Italy.
The CHRS incorporates eight high-risk genetic and clinical prognostic factors, including the type and number of genetic mutations in blood cells, factors related to red blood cell volume, and age over 65. It’s available online.
“You just input the patient’s information and it spits out if the patient is low, intermediate, or high risk for progression to any myeloid malignancy,” Dr. Weeks told her audience.
High-risk patients have about a 50% 10-year cumulative incidence of myeloid malignancy. The large majority of patients are low risk, however, and have a 10-year cumulative incidence of less than 1%. Patients in the middle have a 10-year risk of about 8%.
The low-risk group “is the population of people who probably don’t need to see a specialist,” and can be followed with an annual CBC with their primary care doctors plus further workup with any clinical change. Patients should also be evaluated for cardiovascular and other comorbidity risks.
“It’s the high-risk group we worry most about,” Dr. Weeks said. “We see them more often and repeat the next-generation sequencing” annually with a CBC at least every 6 months and a bone marrow biopsy with any clinical change.
“This is the population we would shuttle towards a clinical trial, as this is the population most likely to benefit,” she said.
The overarching goal of the several ongoing studies in CHIP/CCUS is to find a way to prevent progression to blood cancer. They range from prospective cohorts and single arm pilot studies to randomized clinical trials. One trial is evaluating canakinumab to prevent progression. “Intervention in clonal hematopoiesis might have the dual benefit of both preventing hematologic malignancy as well as reducing [the] inflammatory comorbidities,” Dr. Weeks said.
The reason is that patients will inevitably “go online and see that [the conditions are] associated with lots of bad things; it can really cause patients psychosocial harm if there is no one to explain what their risk is and also provide risk-specific management,” Dr. Weeks said at the annual meeting of the Society of Hematologic Oncology in Houston.
CHIP and CCUS are precursors of myeloid malignancies but for most patients, the risk of progression is less than 1%. CHIPS and CCUS are also associated with cardiovascular, rheumatologic, hepatic, and other diseases.
CHIP is defined by somatic mutations in myeloid malignancy driver genes with a variant allele fraction of 2% or more; CCUS is when those molecular features are accompanied by an unexplained and persistent anemia, thrombocytopenia, or neutropenia.
A small 2017 study suggested that about a third of patients with otherwise unexplained cytopenias have CCUS.
With the increasing use of next generation sequencing for tissue and liquid biopsies and other uses, the incidental diagnosis of both conditions is increasing.
Fortunately, Dr. Weeks’ group recently published a tool for predicting the risk of progression to myeloid malignancy.
Their “clonal hematopoiesis risk score” (CHRS) was developed and validated in over 400,000 healthy volunteers in the UK Biobank, with additional validation in cohorts from Dana Farber and the University of Pavia, Italy.
The CHRS incorporates eight high-risk genetic and clinical prognostic factors, including the type and number of genetic mutations in blood cells, factors related to red blood cell volume, and age over 65. It’s available online.
“You just input the patient’s information and it spits out if the patient is low, intermediate, or high risk for progression to any myeloid malignancy,” Dr. Weeks told her audience.
High-risk patients have about a 50% 10-year cumulative incidence of myeloid malignancy. The large majority of patients are low risk, however, and have a 10-year cumulative incidence of less than 1%. Patients in the middle have a 10-year risk of about 8%.
The low-risk group “is the population of people who probably don’t need to see a specialist,” and can be followed with an annual CBC with their primary care doctors plus further workup with any clinical change. Patients should also be evaluated for cardiovascular and other comorbidity risks.
“It’s the high-risk group we worry most about,” Dr. Weeks said. “We see them more often and repeat the next-generation sequencing” annually with a CBC at least every 6 months and a bone marrow biopsy with any clinical change.
“This is the population we would shuttle towards a clinical trial, as this is the population most likely to benefit,” she said.
The overarching goal of the several ongoing studies in CHIP/CCUS is to find a way to prevent progression to blood cancer. They range from prospective cohorts and single arm pilot studies to randomized clinical trials. One trial is evaluating canakinumab to prevent progression. “Intervention in clonal hematopoiesis might have the dual benefit of both preventing hematologic malignancy as well as reducing [the] inflammatory comorbidities,” Dr. Weeks said.
FROM SOHO 2023
ESMO helps hematologists assess new cancer drugs
It consists of 11 2- to 3-page forms with checklists to grade treatment trials on the extent to which they meet efficacy and safety thresholds. Each of the 11 forms covers a specific trial scenario, such as a randomized controlled trial with curative intent or a trial of a therapy that is not likely to be curative with a primary endpoint of overall survival.
Treatments with curative intent are graded A, B, or C, while treatments in the noncurative setting are graded on a descending scale from 5 to 1. Scores of A and B in the curative setting and 5 and 4 in the noncurative setting represent substantial benefit.
On the form for RCTs with curative intent, for instance, a survival improvement of 5% or more garners an A but an improvement of less than 3% gets a C. Scores are also annotated for serious acute and/or persistent toxicity if present.
The tool, dubbed the ESMO-MCBS:H (European Society for Medical Oncology Magnitude of Clinical Benefit Scale: Hematology), is explained in an article published in Annals of Oncology. The evaluation forms are available online.
The idea behind the work is to help health care professionals and others to more “accurately assess the value of and prioritise therapies for patients with blood cancers. For clinicians, ESMO-MCBS:H will aid in their clinical decision-making and in the development of evidence-based practice and guidelines,” ESMO said in a press release.
To develop ESMO-MCBS:H, the group tailored its tool for evaluating solid tumor therapies, the ESMO-MCBS, to account for the sometimes different endpoints used in hematologic malignancy trials and the very indolent nature of some blood cancers, such as follicular lymphoma, which hampers development of mature data.
Specific changes include adding a new evaluation form to grade single-arm trials with curative intent, such as those used for CAR-T-cell therapies; incorporating molecular surrogate endpoints used in CML trials; and adding a way to grade outcomes for indolent cancers, among others.
The development process included applying the solid tumor tool to 80 blood cancer studies to identify shortcomings and improve its applicability. The final tool was field tested with 51 international experts from EHA and ESMO who largely agreed on the reasonableness of the trial scores.
ESMO said it expects ESMO-MCBS:H will be useful. The solid tumor tool, first published in 2015, is used by the World Health Organization to screen medications for its essential medicines list as well as by ESMO to generate guidelines and oncology centers across Europe to help with resource allocation decisions.
It consists of 11 2- to 3-page forms with checklists to grade treatment trials on the extent to which they meet efficacy and safety thresholds. Each of the 11 forms covers a specific trial scenario, such as a randomized controlled trial with curative intent or a trial of a therapy that is not likely to be curative with a primary endpoint of overall survival.
Treatments with curative intent are graded A, B, or C, while treatments in the noncurative setting are graded on a descending scale from 5 to 1. Scores of A and B in the curative setting and 5 and 4 in the noncurative setting represent substantial benefit.
On the form for RCTs with curative intent, for instance, a survival improvement of 5% or more garners an A but an improvement of less than 3% gets a C. Scores are also annotated for serious acute and/or persistent toxicity if present.
The tool, dubbed the ESMO-MCBS:H (European Society for Medical Oncology Magnitude of Clinical Benefit Scale: Hematology), is explained in an article published in Annals of Oncology. The evaluation forms are available online.
The idea behind the work is to help health care professionals and others to more “accurately assess the value of and prioritise therapies for patients with blood cancers. For clinicians, ESMO-MCBS:H will aid in their clinical decision-making and in the development of evidence-based practice and guidelines,” ESMO said in a press release.
To develop ESMO-MCBS:H, the group tailored its tool for evaluating solid tumor therapies, the ESMO-MCBS, to account for the sometimes different endpoints used in hematologic malignancy trials and the very indolent nature of some blood cancers, such as follicular lymphoma, which hampers development of mature data.
Specific changes include adding a new evaluation form to grade single-arm trials with curative intent, such as those used for CAR-T-cell therapies; incorporating molecular surrogate endpoints used in CML trials; and adding a way to grade outcomes for indolent cancers, among others.
The development process included applying the solid tumor tool to 80 blood cancer studies to identify shortcomings and improve its applicability. The final tool was field tested with 51 international experts from EHA and ESMO who largely agreed on the reasonableness of the trial scores.
ESMO said it expects ESMO-MCBS:H will be useful. The solid tumor tool, first published in 2015, is used by the World Health Organization to screen medications for its essential medicines list as well as by ESMO to generate guidelines and oncology centers across Europe to help with resource allocation decisions.
It consists of 11 2- to 3-page forms with checklists to grade treatment trials on the extent to which they meet efficacy and safety thresholds. Each of the 11 forms covers a specific trial scenario, such as a randomized controlled trial with curative intent or a trial of a therapy that is not likely to be curative with a primary endpoint of overall survival.
Treatments with curative intent are graded A, B, or C, while treatments in the noncurative setting are graded on a descending scale from 5 to 1. Scores of A and B in the curative setting and 5 and 4 in the noncurative setting represent substantial benefit.
On the form for RCTs with curative intent, for instance, a survival improvement of 5% or more garners an A but an improvement of less than 3% gets a C. Scores are also annotated for serious acute and/or persistent toxicity if present.
The tool, dubbed the ESMO-MCBS:H (European Society for Medical Oncology Magnitude of Clinical Benefit Scale: Hematology), is explained in an article published in Annals of Oncology. The evaluation forms are available online.
The idea behind the work is to help health care professionals and others to more “accurately assess the value of and prioritise therapies for patients with blood cancers. For clinicians, ESMO-MCBS:H will aid in their clinical decision-making and in the development of evidence-based practice and guidelines,” ESMO said in a press release.
To develop ESMO-MCBS:H, the group tailored its tool for evaluating solid tumor therapies, the ESMO-MCBS, to account for the sometimes different endpoints used in hematologic malignancy trials and the very indolent nature of some blood cancers, such as follicular lymphoma, which hampers development of mature data.
Specific changes include adding a new evaluation form to grade single-arm trials with curative intent, such as those used for CAR-T-cell therapies; incorporating molecular surrogate endpoints used in CML trials; and adding a way to grade outcomes for indolent cancers, among others.
The development process included applying the solid tumor tool to 80 blood cancer studies to identify shortcomings and improve its applicability. The final tool was field tested with 51 international experts from EHA and ESMO who largely agreed on the reasonableness of the trial scores.
ESMO said it expects ESMO-MCBS:H will be useful. The solid tumor tool, first published in 2015, is used by the World Health Organization to screen medications for its essential medicines list as well as by ESMO to generate guidelines and oncology centers across Europe to help with resource allocation decisions.
FROM ANNALS OF ONCOLOGY
Multiprong strategy makes clinical trials less White
CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.
For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.
When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.
There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.
a period that included a pandemic-induced hiatus in clinical trials in general.
Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.
During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.
Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.
“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.
The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
Program to increase underrepresented patient accrual
The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.
“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.
“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
What works?
The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”
“I’m going to violate the rules of your question,” Dr. Paskett replied.
“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.
She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.
Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:
- Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
- Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
- Translation of informational materials for patients.
- Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
- Real-time monitoring of accrual demographics by the Alliance and at the trial site.
- Closing protocol enrollment to majority populations.
- Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.
The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.
For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.
When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.
There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.
a period that included a pandemic-induced hiatus in clinical trials in general.
Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.
During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.
Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.
“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.
The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
Program to increase underrepresented patient accrual
The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.
“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.
“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
What works?
The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”
“I’m going to violate the rules of your question,” Dr. Paskett replied.
“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.
She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.
Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:
- Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
- Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
- Translation of informational materials for patients.
- Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
- Real-time monitoring of accrual demographics by the Alliance and at the trial site.
- Closing protocol enrollment to majority populations.
- Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.
The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.
For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.
When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.
There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.
a period that included a pandemic-induced hiatus in clinical trials in general.
Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.
During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.
Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.
“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.
The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
Program to increase underrepresented patient accrual
The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.
“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.
“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
What works?
The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”
“I’m going to violate the rules of your question,” Dr. Paskett replied.
“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.
She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.
Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:
- Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
- Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
- Translation of informational materials for patients.
- Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
- Real-time monitoring of accrual demographics by the Alliance and at the trial site.
- Closing protocol enrollment to majority populations.
- Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.
The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT ASCO 2023
CBSM phone app eases anxiety, depression in cancer patients
CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.
Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.
A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.
In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).
However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.
The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.
“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.
“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
Impressive and elegant
“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.
“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.
CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.
To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.
Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.
They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
High-quality control
Ms. Ramiller said that the control app set “a high bar.”
“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.
A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.
The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).
CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)
An extension study of the durability of the effects at 3 and 6 months is underway.
The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.
“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”
The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
A version of this article originally appeared on Medscape.com.
CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.
Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.
A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.
In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).
However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.
The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.
“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.
“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
Impressive and elegant
“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.
“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.
CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.
To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.
Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.
They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
High-quality control
Ms. Ramiller said that the control app set “a high bar.”
“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.
A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.
The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).
CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)
An extension study of the durability of the effects at 3 and 6 months is underway.
The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.
“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”
The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
A version of this article originally appeared on Medscape.com.
CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.
Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.
A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.
In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).
However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.
The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.
“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.
“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
Impressive and elegant
“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.
“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.
CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.
To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.
Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.
They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
High-quality control
Ms. Ramiller said that the control app set “a high bar.”
“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.
A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.
The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).
CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)
An extension study of the durability of the effects at 3 and 6 months is underway.
The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.
“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”
The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
A version of this article originally appeared on Medscape.com.
AT ASCO 2023