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Nationwide hematologists shortage: What’s being done?
Over decades, the shrinking pool of CHs – who are compensated far less than hematologist-oncologists – has put patients at risk without access to adequate and timely care. To alleviate this crisis, individual doctors and national organizations are taking action and making more resources available to CHs and their patients.
`Vicious cycle’
The root cause of the CH shortage can be traced to a dramatic reduction in the number of physicians trained in this field, as Leonard Valentino, MD, President of the National Bleeding Disorders Foundation in New York, explained in an interview.
“There is a vicious cycle where there’s not enough classical hematologists to be program directors, and therefore trainees are often steered to fellowships in oncology,” said Dr. Valentino.
According to data published in JAMA, in 1995 there were 74 classical hematology programs in the United States; by 2018, there were only 2, During this same time period, the number of combined hematology/oncology training programs (HOPs) nearly doubled, from 75 to 146. However, it is estimated that less than 5% of graduates of adult HOPs pursued a career in classical hematology, as reported in Blood Advances. This low percentage can be attributed, at least in part, to the emphasis that most HOPs place on oncology.
Dr. Valentino noted that financial pressures are also diverting medical students from becoming CHs, adding that a hematologist-oncologist can make three times the annual salary of a CH.
Furthermore, when CHs treat bleeding and clotting disorders, they often need to meet with a patient for a 60- to 90-minute initial consultation, then they go on to provide a lifetime of labor-intensive care.
“This work is neither verticalized [that is, supported by radiologists, surgeons, and a cadre of nurses], nor is it billable per hour on a scale comparable to what oncologists can charge,” Dr. Valentino explained.
The survey published in Blood Advances illustrates the consequences of such a disparity in income potential: 34% of hematology/oncology fellows surveyed were likely to enter solid tumor oncology, while 20% and 4.6% would proceed to malignant hematology and CH, respectively.
Toll on patients
Primary care doctors treat some common blood disorders, but they almost always refer more difficult or complicated cases to a shrinking population of CHs.
“For many Americans, it is getting more difficult to find providers who subspecialize in hemostasis and thrombosis disorders. Patients can expect prolonged waiting times to get evaluated after a referral” said Mukul Singal, MD, of the Indiana Hemophilia and Thrombosis Center in Indianapolis.
Dr. Singal said the shortage is so acute that “at many institutions, malignant hematologists or oncologists are having to staff in-patient hematology consult services and see outpatient classical hematology patients. General hematologist/oncologists or medical oncologists are often not as comfortable or experienced with dealing with some of the complex CH conditions.”
A working care model, without enough doctors
In 1975, responding to patient advocacy groups, the federal government began funding hemophilia treatment centers (HTCs). Such centers offer a comprehensive care model that gives patients access to practitioners and administrative staff with the expertise to help them stay as healthy as possible. According to the Centers for Disease Control and Prevention, people with hemophilia who used an HTC were 40% less likely to die of a hemophilia-related complication and 40% less likely to be hospitalized for bleeding complications, compared to those who did not receive such specialized care.
“HTCs are effective at keeping patients out of the hospital and engaged in their lives. Between 80% and 95% of hemophilia patients get their care from an HTC and more patients want more services from them,” said Joe Pugliese, president of the Hemophilia Alliance in Lansdale, Pa.
Expanding care to meet patient demand is challenged by the restrictions on doctors’ salaries. All 140 U.S.-based HTCs share a $4.9 million federal grant but, by law, they can’t pay any provider more than $211,000 a year. “These restrictions push many people to industry, leaving too few doctors to meet patient demand,” Mr. Pugliese explained.
The fact that most HTCs are located in or near major cities also presents patients with the challenge of commuting, sometimes across state lines, to see a specialist. However, an uptick in telemedicine has provided one bright spot for many patients, allowing care to be brought to them.
The Hemophilia Alliance is also working on a multifaceted approach to change the rules, so that CHs are offered better compensation. “We have lobbyists in Washington, as well as an advocacy committee and a payer committee working to better support the HTC model,” Mr. Pugliese said.
Beyond the paycheck: Supporting CHs and patients
As market and regulatory restrictions make it difficult to boost the pay of CHs, doctors and nonprofit organizations are collaborating to support young CHs and bring more into the field. The American Society of Hematology has started and fully funded the Hematology Focused Fellowship Training Program (HFFTP). This program pairs comprehensive classical hematology training with education in transfusion medicine, sickle cell disease, hemostasis/thrombosis, systems-based hematology, health equity research, and global health. According to the program’s website, HFFTP’s goal is to add 50 new academic hematologists nationwide by 2030, in an effort to “improve the lives of patients with blood and bone marrow disorders.”
Additionally, classic hematologists are aiming to attract younger physicians and trainees to their field by introducing them to the various rewarding aspects of dealing with patients with inherited, chronic blood diseases. Programs like the Partners Physicians Academy (PPA), a 5-day training course that is specifically designed to encourage and retain young hematology students as classical hematologists, are essential to this effort.
“Along with preparing physicians to work in an HTC, programs like the Hematology Focused Fellowship Training Program and the Partners Physicians Academy are so important because they might convince young doctors to stick with non–oncology-based hematology careers, through the right mix of knowing about exciting research like gene therapy, financial and mentorship support, and a desire to meet unmet medical need,” explained Dr. Valentino.
The next PPA is taking place Sept. 18-22 in Indianapolis.
Dr. Singal, Dr. Valentino, and Mr. Pugliese had no financial disclosures to report.
Over decades, the shrinking pool of CHs – who are compensated far less than hematologist-oncologists – has put patients at risk without access to adequate and timely care. To alleviate this crisis, individual doctors and national organizations are taking action and making more resources available to CHs and their patients.
`Vicious cycle’
The root cause of the CH shortage can be traced to a dramatic reduction in the number of physicians trained in this field, as Leonard Valentino, MD, President of the National Bleeding Disorders Foundation in New York, explained in an interview.
“There is a vicious cycle where there’s not enough classical hematologists to be program directors, and therefore trainees are often steered to fellowships in oncology,” said Dr. Valentino.
According to data published in JAMA, in 1995 there were 74 classical hematology programs in the United States; by 2018, there were only 2, During this same time period, the number of combined hematology/oncology training programs (HOPs) nearly doubled, from 75 to 146. However, it is estimated that less than 5% of graduates of adult HOPs pursued a career in classical hematology, as reported in Blood Advances. This low percentage can be attributed, at least in part, to the emphasis that most HOPs place on oncology.
Dr. Valentino noted that financial pressures are also diverting medical students from becoming CHs, adding that a hematologist-oncologist can make three times the annual salary of a CH.
Furthermore, when CHs treat bleeding and clotting disorders, they often need to meet with a patient for a 60- to 90-minute initial consultation, then they go on to provide a lifetime of labor-intensive care.
“This work is neither verticalized [that is, supported by radiologists, surgeons, and a cadre of nurses], nor is it billable per hour on a scale comparable to what oncologists can charge,” Dr. Valentino explained.
The survey published in Blood Advances illustrates the consequences of such a disparity in income potential: 34% of hematology/oncology fellows surveyed were likely to enter solid tumor oncology, while 20% and 4.6% would proceed to malignant hematology and CH, respectively.
Toll on patients
Primary care doctors treat some common blood disorders, but they almost always refer more difficult or complicated cases to a shrinking population of CHs.
“For many Americans, it is getting more difficult to find providers who subspecialize in hemostasis and thrombosis disorders. Patients can expect prolonged waiting times to get evaluated after a referral” said Mukul Singal, MD, of the Indiana Hemophilia and Thrombosis Center in Indianapolis.
Dr. Singal said the shortage is so acute that “at many institutions, malignant hematologists or oncologists are having to staff in-patient hematology consult services and see outpatient classical hematology patients. General hematologist/oncologists or medical oncologists are often not as comfortable or experienced with dealing with some of the complex CH conditions.”
A working care model, without enough doctors
In 1975, responding to patient advocacy groups, the federal government began funding hemophilia treatment centers (HTCs). Such centers offer a comprehensive care model that gives patients access to practitioners and administrative staff with the expertise to help them stay as healthy as possible. According to the Centers for Disease Control and Prevention, people with hemophilia who used an HTC were 40% less likely to die of a hemophilia-related complication and 40% less likely to be hospitalized for bleeding complications, compared to those who did not receive such specialized care.
“HTCs are effective at keeping patients out of the hospital and engaged in their lives. Between 80% and 95% of hemophilia patients get their care from an HTC and more patients want more services from them,” said Joe Pugliese, president of the Hemophilia Alliance in Lansdale, Pa.
Expanding care to meet patient demand is challenged by the restrictions on doctors’ salaries. All 140 U.S.-based HTCs share a $4.9 million federal grant but, by law, they can’t pay any provider more than $211,000 a year. “These restrictions push many people to industry, leaving too few doctors to meet patient demand,” Mr. Pugliese explained.
The fact that most HTCs are located in or near major cities also presents patients with the challenge of commuting, sometimes across state lines, to see a specialist. However, an uptick in telemedicine has provided one bright spot for many patients, allowing care to be brought to them.
The Hemophilia Alliance is also working on a multifaceted approach to change the rules, so that CHs are offered better compensation. “We have lobbyists in Washington, as well as an advocacy committee and a payer committee working to better support the HTC model,” Mr. Pugliese said.
Beyond the paycheck: Supporting CHs and patients
As market and regulatory restrictions make it difficult to boost the pay of CHs, doctors and nonprofit organizations are collaborating to support young CHs and bring more into the field. The American Society of Hematology has started and fully funded the Hematology Focused Fellowship Training Program (HFFTP). This program pairs comprehensive classical hematology training with education in transfusion medicine, sickle cell disease, hemostasis/thrombosis, systems-based hematology, health equity research, and global health. According to the program’s website, HFFTP’s goal is to add 50 new academic hematologists nationwide by 2030, in an effort to “improve the lives of patients with blood and bone marrow disorders.”
Additionally, classic hematologists are aiming to attract younger physicians and trainees to their field by introducing them to the various rewarding aspects of dealing with patients with inherited, chronic blood diseases. Programs like the Partners Physicians Academy (PPA), a 5-day training course that is specifically designed to encourage and retain young hematology students as classical hematologists, are essential to this effort.
“Along with preparing physicians to work in an HTC, programs like the Hematology Focused Fellowship Training Program and the Partners Physicians Academy are so important because they might convince young doctors to stick with non–oncology-based hematology careers, through the right mix of knowing about exciting research like gene therapy, financial and mentorship support, and a desire to meet unmet medical need,” explained Dr. Valentino.
The next PPA is taking place Sept. 18-22 in Indianapolis.
Dr. Singal, Dr. Valentino, and Mr. Pugliese had no financial disclosures to report.
Over decades, the shrinking pool of CHs – who are compensated far less than hematologist-oncologists – has put patients at risk without access to adequate and timely care. To alleviate this crisis, individual doctors and national organizations are taking action and making more resources available to CHs and their patients.
`Vicious cycle’
The root cause of the CH shortage can be traced to a dramatic reduction in the number of physicians trained in this field, as Leonard Valentino, MD, President of the National Bleeding Disorders Foundation in New York, explained in an interview.
“There is a vicious cycle where there’s not enough classical hematologists to be program directors, and therefore trainees are often steered to fellowships in oncology,” said Dr. Valentino.
According to data published in JAMA, in 1995 there were 74 classical hematology programs in the United States; by 2018, there were only 2, During this same time period, the number of combined hematology/oncology training programs (HOPs) nearly doubled, from 75 to 146. However, it is estimated that less than 5% of graduates of adult HOPs pursued a career in classical hematology, as reported in Blood Advances. This low percentage can be attributed, at least in part, to the emphasis that most HOPs place on oncology.
Dr. Valentino noted that financial pressures are also diverting medical students from becoming CHs, adding that a hematologist-oncologist can make three times the annual salary of a CH.
Furthermore, when CHs treat bleeding and clotting disorders, they often need to meet with a patient for a 60- to 90-minute initial consultation, then they go on to provide a lifetime of labor-intensive care.
“This work is neither verticalized [that is, supported by radiologists, surgeons, and a cadre of nurses], nor is it billable per hour on a scale comparable to what oncologists can charge,” Dr. Valentino explained.
The survey published in Blood Advances illustrates the consequences of such a disparity in income potential: 34% of hematology/oncology fellows surveyed were likely to enter solid tumor oncology, while 20% and 4.6% would proceed to malignant hematology and CH, respectively.
Toll on patients
Primary care doctors treat some common blood disorders, but they almost always refer more difficult or complicated cases to a shrinking population of CHs.
“For many Americans, it is getting more difficult to find providers who subspecialize in hemostasis and thrombosis disorders. Patients can expect prolonged waiting times to get evaluated after a referral” said Mukul Singal, MD, of the Indiana Hemophilia and Thrombosis Center in Indianapolis.
Dr. Singal said the shortage is so acute that “at many institutions, malignant hematologists or oncologists are having to staff in-patient hematology consult services and see outpatient classical hematology patients. General hematologist/oncologists or medical oncologists are often not as comfortable or experienced with dealing with some of the complex CH conditions.”
A working care model, without enough doctors
In 1975, responding to patient advocacy groups, the federal government began funding hemophilia treatment centers (HTCs). Such centers offer a comprehensive care model that gives patients access to practitioners and administrative staff with the expertise to help them stay as healthy as possible. According to the Centers for Disease Control and Prevention, people with hemophilia who used an HTC were 40% less likely to die of a hemophilia-related complication and 40% less likely to be hospitalized for bleeding complications, compared to those who did not receive such specialized care.
“HTCs are effective at keeping patients out of the hospital and engaged in their lives. Between 80% and 95% of hemophilia patients get their care from an HTC and more patients want more services from them,” said Joe Pugliese, president of the Hemophilia Alliance in Lansdale, Pa.
Expanding care to meet patient demand is challenged by the restrictions on doctors’ salaries. All 140 U.S.-based HTCs share a $4.9 million federal grant but, by law, they can’t pay any provider more than $211,000 a year. “These restrictions push many people to industry, leaving too few doctors to meet patient demand,” Mr. Pugliese explained.
The fact that most HTCs are located in or near major cities also presents patients with the challenge of commuting, sometimes across state lines, to see a specialist. However, an uptick in telemedicine has provided one bright spot for many patients, allowing care to be brought to them.
The Hemophilia Alliance is also working on a multifaceted approach to change the rules, so that CHs are offered better compensation. “We have lobbyists in Washington, as well as an advocacy committee and a payer committee working to better support the HTC model,” Mr. Pugliese said.
Beyond the paycheck: Supporting CHs and patients
As market and regulatory restrictions make it difficult to boost the pay of CHs, doctors and nonprofit organizations are collaborating to support young CHs and bring more into the field. The American Society of Hematology has started and fully funded the Hematology Focused Fellowship Training Program (HFFTP). This program pairs comprehensive classical hematology training with education in transfusion medicine, sickle cell disease, hemostasis/thrombosis, systems-based hematology, health equity research, and global health. According to the program’s website, HFFTP’s goal is to add 50 new academic hematologists nationwide by 2030, in an effort to “improve the lives of patients with blood and bone marrow disorders.”
Additionally, classic hematologists are aiming to attract younger physicians and trainees to their field by introducing them to the various rewarding aspects of dealing with patients with inherited, chronic blood diseases. Programs like the Partners Physicians Academy (PPA), a 5-day training course that is specifically designed to encourage and retain young hematology students as classical hematologists, are essential to this effort.
“Along with preparing physicians to work in an HTC, programs like the Hematology Focused Fellowship Training Program and the Partners Physicians Academy are so important because they might convince young doctors to stick with non–oncology-based hematology careers, through the right mix of knowing about exciting research like gene therapy, financial and mentorship support, and a desire to meet unmet medical need,” explained Dr. Valentino.
The next PPA is taking place Sept. 18-22 in Indianapolis.
Dr. Singal, Dr. Valentino, and Mr. Pugliese had no financial disclosures to report.
FDA approves JAK inhibitor momelotinib for myelofibrosis with anemia
Momelotinib is the fourth JAK inhibitor to be approved by the agency for myelofibrosis but the only one indicated for patients with hemoglobin levels below 10 g/dL.
It’s an important development because, while JAK inhibitors are standard treatment for myelofibrosis, those previously approved for the uncommon blood cancer can cause cytopenia, particularly anemia, which, ironically, is also a hallmark of myelofibrosis itself.
This issue makes using JAK inhibitors for myelofibrosis challenging, according to Anthony Hunter, MD, a myeloid malignancies specialist at Emory University, Atlanta, who spoke on the topic recently at the annual meeting of the Society of Hematologic Oncology in Houston. “Momelotinib is an important emerging agent for these more anemic patients.” Momelotinib has a spleen response comparable with ruxolitinib – the first JAK inhibitor approved for myelofibrosis in the United States – and significantly higher rates of transfusion independence, although lower rates of symptom control, he said.
In GSK’s press release, hematologist/oncologist Ruben Mesa, MD, executive director of Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, N.C., said that, “with momelotinib, we have the potential to establish a new standard of care for myelofibrosis patients with anemia.”
Momelotinib’s specific indication is for “the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post–polycythemia vera and post–essential thrombocythemia), in adults with anemia.”
The once-daily oral medication was approved based on two trials. One trial, MOMENTUM, showed statistically significant response with respect to constitutional symptoms, splenic response, and transfusion independence in anemic patients treated with momelotinib versus danazol.
An anemic subset of the SIMPLIFY-1 trial showed comparable spleen volume reduction versus ruxolitinib but a numerically lower symptom response rate.
The most common momelotinib adverse reactions in trials were thrombocytopenia, hemorrhage, bacterial infection, fatigue, dizziness, diarrhea, and nausea.
A version of this article appeared on Medscape.com.
Momelotinib is the fourth JAK inhibitor to be approved by the agency for myelofibrosis but the only one indicated for patients with hemoglobin levels below 10 g/dL.
It’s an important development because, while JAK inhibitors are standard treatment for myelofibrosis, those previously approved for the uncommon blood cancer can cause cytopenia, particularly anemia, which, ironically, is also a hallmark of myelofibrosis itself.
This issue makes using JAK inhibitors for myelofibrosis challenging, according to Anthony Hunter, MD, a myeloid malignancies specialist at Emory University, Atlanta, who spoke on the topic recently at the annual meeting of the Society of Hematologic Oncology in Houston. “Momelotinib is an important emerging agent for these more anemic patients.” Momelotinib has a spleen response comparable with ruxolitinib – the first JAK inhibitor approved for myelofibrosis in the United States – and significantly higher rates of transfusion independence, although lower rates of symptom control, he said.
In GSK’s press release, hematologist/oncologist Ruben Mesa, MD, executive director of Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, N.C., said that, “with momelotinib, we have the potential to establish a new standard of care for myelofibrosis patients with anemia.”
Momelotinib’s specific indication is for “the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post–polycythemia vera and post–essential thrombocythemia), in adults with anemia.”
The once-daily oral medication was approved based on two trials. One trial, MOMENTUM, showed statistically significant response with respect to constitutional symptoms, splenic response, and transfusion independence in anemic patients treated with momelotinib versus danazol.
An anemic subset of the SIMPLIFY-1 trial showed comparable spleen volume reduction versus ruxolitinib but a numerically lower symptom response rate.
The most common momelotinib adverse reactions in trials were thrombocytopenia, hemorrhage, bacterial infection, fatigue, dizziness, diarrhea, and nausea.
A version of this article appeared on Medscape.com.
Momelotinib is the fourth JAK inhibitor to be approved by the agency for myelofibrosis but the only one indicated for patients with hemoglobin levels below 10 g/dL.
It’s an important development because, while JAK inhibitors are standard treatment for myelofibrosis, those previously approved for the uncommon blood cancer can cause cytopenia, particularly anemia, which, ironically, is also a hallmark of myelofibrosis itself.
This issue makes using JAK inhibitors for myelofibrosis challenging, according to Anthony Hunter, MD, a myeloid malignancies specialist at Emory University, Atlanta, who spoke on the topic recently at the annual meeting of the Society of Hematologic Oncology in Houston. “Momelotinib is an important emerging agent for these more anemic patients.” Momelotinib has a spleen response comparable with ruxolitinib – the first JAK inhibitor approved for myelofibrosis in the United States – and significantly higher rates of transfusion independence, although lower rates of symptom control, he said.
In GSK’s press release, hematologist/oncologist Ruben Mesa, MD, executive director of Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, N.C., said that, “with momelotinib, we have the potential to establish a new standard of care for myelofibrosis patients with anemia.”
Momelotinib’s specific indication is for “the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post–polycythemia vera and post–essential thrombocythemia), in adults with anemia.”
The once-daily oral medication was approved based on two trials. One trial, MOMENTUM, showed statistically significant response with respect to constitutional symptoms, splenic response, and transfusion independence in anemic patients treated with momelotinib versus danazol.
An anemic subset of the SIMPLIFY-1 trial showed comparable spleen volume reduction versus ruxolitinib but a numerically lower symptom response rate.
The most common momelotinib adverse reactions in trials were thrombocytopenia, hemorrhage, bacterial infection, fatigue, dizziness, diarrhea, and nausea.
A version of this article appeared on Medscape.com.
Artificial intelligence in your office
It is difficult to go through any publication or website these days without finding an article about artificial intelligence (AI). Many discuss its current status, while others speculate on potential future applications. Often, AI is described as an “existential threat to human health” by commentators who aren’t even aware of the definition of that term as Kierkegaard conceived it, the role of the individual to breathe meaning into life. Others characterize such cataclysmic predictions as “overblown and misdirected”.
The long-term potential for abuse of AI requires discussion, and should be addressed by policy makers, but that is beyond the scope of this column.
Meanwhile, with no “existential” threat to anybody.
The most popular current AI-based medical applications are automated scribes. They transcribe live consultations between physician and patient automatically and create a searchable report, plus notes for charts and billing.
I’ve written about AI scribes before, but the quality and user-friendliness of these products have improved dramatically in recent years. Language processing capabilities now permit you to speak naturally, without having to memorize specific commands. Some scribes can mimic your writing style based on sample notes that you enter into the system. Others allow you to integrate your own knowledge base, or a bibliography of research studies. With some systems, you can dictate notes directly into most EHR software, ask questions regarding medication dosages, or access a patient’s medical history from hospitals or other offices.
Current popular medical scribe products include DeepCura, DeepScribe, Nuance, Suki, Augmedix, Tali AI, Iodine Software, and ScribeLink. Amazon Web Services recently launched its own product, HealthScribe, as well. (As always, I have no financial interest in any product or service mentioned in this column.)
AI scribes aren’t entirely autonomous, of course; you need to read the output and check for potential inaccuracies. Still, users claim that they substantially reduce documentation and charting time, permitting more patient visits and less after-hours work.
AI can also be used to provide useful content for your patients. If you are not particularly good at writing, or don’t have the time for it, generative algorithms like the much-vaunted ChatGPT can generate posts, FAQs, and other informational content for your website, blog, or social media pages. You can ask for ideas about timely health topics and write general information articles, or create content specific to your location or specialty. You can use it to write emails informing your patients about upcoming office events or educate them on a range of topics, from getting their annual flu shots to scheduling regular screening skin exams.
With some of the same techniques and additional software, you can create entire videos for your website at a fraction of the cost of hiring a video production team. After using ChatGPT to write the content – for example, a 5-minute script on the importance of sunscreen in preventing skin cancer – you can employ a text-to-speech algorithm such as Revoicer to transform the script into audio content, and then a preproduction algorithm like Yepic or Synthesia to generate a video with a synthetic human.
If you are unhappy with your current online presence, you can use AI to create an entire website. Through a series of questions, AI website builders such as Wix ADI, Jimdo, Hostinger, and 10Web gather all the information needed to set up a website draft that is already personalized with medical-specific content. Most offer the option to connect to Instagram, Facebook, Google My Business, and similar sites, to which they can import your office’s logo, images, and descriptive texts.
Some of them are capable of pulling up responsive site pages that automatically adjust to the device – mobile or computer – that the visitor is using. This is important, as I’ve written before, because more than half of all searches for doctors are now made on smartphones, so the more “mobile friendly” your site is, the higher it will be ranked. You can test how easily a visitor can use your website on a mobile device with Google’s free Mobile-Friendly Test.
If you give talks at medical meetings, you know how cumbersome and time-consuming it can be to create Powerpoint presentations. Once again, AI can save you time and trouble. Presentation designers such as Presentations.AI, Deck Robot, iA Presenter, and Beautiful.AI can assemble very acceptable presentations from your primary inputs. You typically choose a template, input your basic data, and AI will format the slides and offer you visuals, animations, voice-overs, and other fancy features. You will also have flexibility in changing segments or images or sizes you don’t like.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
It is difficult to go through any publication or website these days without finding an article about artificial intelligence (AI). Many discuss its current status, while others speculate on potential future applications. Often, AI is described as an “existential threat to human health” by commentators who aren’t even aware of the definition of that term as Kierkegaard conceived it, the role of the individual to breathe meaning into life. Others characterize such cataclysmic predictions as “overblown and misdirected”.
The long-term potential for abuse of AI requires discussion, and should be addressed by policy makers, but that is beyond the scope of this column.
Meanwhile, with no “existential” threat to anybody.
The most popular current AI-based medical applications are automated scribes. They transcribe live consultations between physician and patient automatically and create a searchable report, plus notes for charts and billing.
I’ve written about AI scribes before, but the quality and user-friendliness of these products have improved dramatically in recent years. Language processing capabilities now permit you to speak naturally, without having to memorize specific commands. Some scribes can mimic your writing style based on sample notes that you enter into the system. Others allow you to integrate your own knowledge base, or a bibliography of research studies. With some systems, you can dictate notes directly into most EHR software, ask questions regarding medication dosages, or access a patient’s medical history from hospitals or other offices.
Current popular medical scribe products include DeepCura, DeepScribe, Nuance, Suki, Augmedix, Tali AI, Iodine Software, and ScribeLink. Amazon Web Services recently launched its own product, HealthScribe, as well. (As always, I have no financial interest in any product or service mentioned in this column.)
AI scribes aren’t entirely autonomous, of course; you need to read the output and check for potential inaccuracies. Still, users claim that they substantially reduce documentation and charting time, permitting more patient visits and less after-hours work.
AI can also be used to provide useful content for your patients. If you are not particularly good at writing, or don’t have the time for it, generative algorithms like the much-vaunted ChatGPT can generate posts, FAQs, and other informational content for your website, blog, or social media pages. You can ask for ideas about timely health topics and write general information articles, or create content specific to your location or specialty. You can use it to write emails informing your patients about upcoming office events or educate them on a range of topics, from getting their annual flu shots to scheduling regular screening skin exams.
With some of the same techniques and additional software, you can create entire videos for your website at a fraction of the cost of hiring a video production team. After using ChatGPT to write the content – for example, a 5-minute script on the importance of sunscreen in preventing skin cancer – you can employ a text-to-speech algorithm such as Revoicer to transform the script into audio content, and then a preproduction algorithm like Yepic or Synthesia to generate a video with a synthetic human.
If you are unhappy with your current online presence, you can use AI to create an entire website. Through a series of questions, AI website builders such as Wix ADI, Jimdo, Hostinger, and 10Web gather all the information needed to set up a website draft that is already personalized with medical-specific content. Most offer the option to connect to Instagram, Facebook, Google My Business, and similar sites, to which they can import your office’s logo, images, and descriptive texts.
Some of them are capable of pulling up responsive site pages that automatically adjust to the device – mobile or computer – that the visitor is using. This is important, as I’ve written before, because more than half of all searches for doctors are now made on smartphones, so the more “mobile friendly” your site is, the higher it will be ranked. You can test how easily a visitor can use your website on a mobile device with Google’s free Mobile-Friendly Test.
If you give talks at medical meetings, you know how cumbersome and time-consuming it can be to create Powerpoint presentations. Once again, AI can save you time and trouble. Presentation designers such as Presentations.AI, Deck Robot, iA Presenter, and Beautiful.AI can assemble very acceptable presentations from your primary inputs. You typically choose a template, input your basic data, and AI will format the slides and offer you visuals, animations, voice-overs, and other fancy features. You will also have flexibility in changing segments or images or sizes you don’t like.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
It is difficult to go through any publication or website these days without finding an article about artificial intelligence (AI). Many discuss its current status, while others speculate on potential future applications. Often, AI is described as an “existential threat to human health” by commentators who aren’t even aware of the definition of that term as Kierkegaard conceived it, the role of the individual to breathe meaning into life. Others characterize such cataclysmic predictions as “overblown and misdirected”.
The long-term potential for abuse of AI requires discussion, and should be addressed by policy makers, but that is beyond the scope of this column.
Meanwhile, with no “existential” threat to anybody.
The most popular current AI-based medical applications are automated scribes. They transcribe live consultations between physician and patient automatically and create a searchable report, plus notes for charts and billing.
I’ve written about AI scribes before, but the quality and user-friendliness of these products have improved dramatically in recent years. Language processing capabilities now permit you to speak naturally, without having to memorize specific commands. Some scribes can mimic your writing style based on sample notes that you enter into the system. Others allow you to integrate your own knowledge base, or a bibliography of research studies. With some systems, you can dictate notes directly into most EHR software, ask questions regarding medication dosages, or access a patient’s medical history from hospitals or other offices.
Current popular medical scribe products include DeepCura, DeepScribe, Nuance, Suki, Augmedix, Tali AI, Iodine Software, and ScribeLink. Amazon Web Services recently launched its own product, HealthScribe, as well. (As always, I have no financial interest in any product or service mentioned in this column.)
AI scribes aren’t entirely autonomous, of course; you need to read the output and check for potential inaccuracies. Still, users claim that they substantially reduce documentation and charting time, permitting more patient visits and less after-hours work.
AI can also be used to provide useful content for your patients. If you are not particularly good at writing, or don’t have the time for it, generative algorithms like the much-vaunted ChatGPT can generate posts, FAQs, and other informational content for your website, blog, or social media pages. You can ask for ideas about timely health topics and write general information articles, or create content specific to your location or specialty. You can use it to write emails informing your patients about upcoming office events or educate them on a range of topics, from getting their annual flu shots to scheduling regular screening skin exams.
With some of the same techniques and additional software, you can create entire videos for your website at a fraction of the cost of hiring a video production team. After using ChatGPT to write the content – for example, a 5-minute script on the importance of sunscreen in preventing skin cancer – you can employ a text-to-speech algorithm such as Revoicer to transform the script into audio content, and then a preproduction algorithm like Yepic or Synthesia to generate a video with a synthetic human.
If you are unhappy with your current online presence, you can use AI to create an entire website. Through a series of questions, AI website builders such as Wix ADI, Jimdo, Hostinger, and 10Web gather all the information needed to set up a website draft that is already personalized with medical-specific content. Most offer the option to connect to Instagram, Facebook, Google My Business, and similar sites, to which they can import your office’s logo, images, and descriptive texts.
Some of them are capable of pulling up responsive site pages that automatically adjust to the device – mobile or computer – that the visitor is using. This is important, as I’ve written before, because more than half of all searches for doctors are now made on smartphones, so the more “mobile friendly” your site is, the higher it will be ranked. You can test how easily a visitor can use your website on a mobile device with Google’s free Mobile-Friendly Test.
If you give talks at medical meetings, you know how cumbersome and time-consuming it can be to create Powerpoint presentations. Once again, AI can save you time and trouble. Presentation designers such as Presentations.AI, Deck Robot, iA Presenter, and Beautiful.AI can assemble very acceptable presentations from your primary inputs. You typically choose a template, input your basic data, and AI will format the slides and offer you visuals, animations, voice-overs, and other fancy features. You will also have flexibility in changing segments or images or sizes you don’t like.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
Debate: Should smoldering myeloma be treated?
Hematologist Sagar Lonial, MD, a multiple myeloma specialist and researcher at Emory University, Atlanta, argued for treatment. Hematologist Angela Dispenzieri, MD, also a myeloma researcher and specialist at the Mayo Clinic in Rochester, Minn., took the opposing side, arguing for watchful waiting.
The two experts based their arguments largely on the same two studies, the only randomized trials to tackle the issue to date. While Dr. Dispenzieri focused on their shortcomings, Dr. Lonial focused on their strengths.
In a poll after the debate, about a third of audience members agreed that watchful waiting is the way to go, but about two-thirds favored a personalized approach to smoldering myeloma treatment based on patient risk.
“I’m taking this as a win,” Dr. Lonial said.
Different interpretations of two trials
The first of the two trials recruited from 2007 to 2010 and was conducted in Spain and Portugal. Fifty-seven high-risk patients were randomized to lenalidomide plus dexamethasone (Len-Dex) for up to 2 years; 62 others were randomized to observation.
At 3 years, 70% of observed patients had progressed to multiple myeloma versus only 20% in the Len-Dex group; 82% of Len-Dex patients were alive at data cut-off in 2015 versus 64% of observation patients.
The second, more recent trial, which was led by Dr. Lonial, randomized 92 intermediate or high-risk smoldering myeloma patients to lenalidomide alone for a median of 2 years and 90 others to observation. Three-year progression-free survival (PFS) was 91% in the treatment arm versus 66% with observation. Overall survival data have not yet been reported.
Dr. Dispenzieri acknowledged that the results from Spain and Portugal are impressive. “Treating with Len-Dex gives you a far superior freedom from progression. ... Overall survival was better too.” Results for Len-Dex were “fantastic,” she said.
However, the trial was done before myeloma-defining event criteria existed, so it’s very likely that the treatment arm in the Spanish study included actual myeloma cases, she said.
About 46% of treated patients in Dr. Lonial’s study met the current definition for high risk for progression based on the 2-20-20 rule, which Dr. Dispenzieri helped develop. Although there was an improvement in PFS in the high-risk group, there was no significant improvement for intermediate- and low-risk subjects. Also, more than 80% of observed patients hadn’t progressed by 2 years, and overall survival data are missing.
Meanwhile, treated patients in both trials had more adverse events, including secondary malignancies, and there’s the possibility that early treatment may make patients resistant to treatment later on when they progress to multiple myeloma, although that didn’t seem to happen in the Spanish trial.
“Of course, we want to prevent morbidity, of course we would love to cure the disease,” but “should we treat high-risk smoldering myeloma patients based on overall survival data from a trial of” just 119 “patients that may have been contaminated with actual myeloma” cases? Is it ethical to treat low- and intermediate-risk patients who have only a 50% chance of developing myeloma after 10 years?”
Her answer to both questions was “no and no. ... There’s just a lot of work to be done” to better understand the condition and when and how to intervene. In the meantime, “don’t treat smoldering melanoma patients” outside of a trial, she said.
“First, do no harm,” Dr. Dispenzieri cautioned in her final slide.
Dr. Lonial said he agreed with many of Dr. Dispenzieri’s points, but disagreed with her conclusion not to treat.
“Everybody can always be critical of randomized trials, but at the end of the day, we now have two randomized phase 3 trials comparing early intervention with no intervention demonstrating a significant delay in developing myeloma. I think it’s time to end the ‘we need more data; we need more trials.’ It’s time for us to take a stand.”
He argued for 2 years of lenalidomide for patients who meet the 2-20-20 high-risk definition, based on the median time people were treated in his trial.
He said he discusses the option “with every smoldering patient [who] walks in to see me” if they aren’t eligible for a trial.
Dr. Lonial mentioned his team is currently pulling together longer-term survival data for their trial.
Hematologist Sagar Lonial, MD, a multiple myeloma specialist and researcher at Emory University, Atlanta, argued for treatment. Hematologist Angela Dispenzieri, MD, also a myeloma researcher and specialist at the Mayo Clinic in Rochester, Minn., took the opposing side, arguing for watchful waiting.
The two experts based their arguments largely on the same two studies, the only randomized trials to tackle the issue to date. While Dr. Dispenzieri focused on their shortcomings, Dr. Lonial focused on their strengths.
In a poll after the debate, about a third of audience members agreed that watchful waiting is the way to go, but about two-thirds favored a personalized approach to smoldering myeloma treatment based on patient risk.
“I’m taking this as a win,” Dr. Lonial said.
Different interpretations of two trials
The first of the two trials recruited from 2007 to 2010 and was conducted in Spain and Portugal. Fifty-seven high-risk patients were randomized to lenalidomide plus dexamethasone (Len-Dex) for up to 2 years; 62 others were randomized to observation.
At 3 years, 70% of observed patients had progressed to multiple myeloma versus only 20% in the Len-Dex group; 82% of Len-Dex patients were alive at data cut-off in 2015 versus 64% of observation patients.
The second, more recent trial, which was led by Dr. Lonial, randomized 92 intermediate or high-risk smoldering myeloma patients to lenalidomide alone for a median of 2 years and 90 others to observation. Three-year progression-free survival (PFS) was 91% in the treatment arm versus 66% with observation. Overall survival data have not yet been reported.
Dr. Dispenzieri acknowledged that the results from Spain and Portugal are impressive. “Treating with Len-Dex gives you a far superior freedom from progression. ... Overall survival was better too.” Results for Len-Dex were “fantastic,” she said.
However, the trial was done before myeloma-defining event criteria existed, so it’s very likely that the treatment arm in the Spanish study included actual myeloma cases, she said.
About 46% of treated patients in Dr. Lonial’s study met the current definition for high risk for progression based on the 2-20-20 rule, which Dr. Dispenzieri helped develop. Although there was an improvement in PFS in the high-risk group, there was no significant improvement for intermediate- and low-risk subjects. Also, more than 80% of observed patients hadn’t progressed by 2 years, and overall survival data are missing.
Meanwhile, treated patients in both trials had more adverse events, including secondary malignancies, and there’s the possibility that early treatment may make patients resistant to treatment later on when they progress to multiple myeloma, although that didn’t seem to happen in the Spanish trial.
“Of course, we want to prevent morbidity, of course we would love to cure the disease,” but “should we treat high-risk smoldering myeloma patients based on overall survival data from a trial of” just 119 “patients that may have been contaminated with actual myeloma” cases? Is it ethical to treat low- and intermediate-risk patients who have only a 50% chance of developing myeloma after 10 years?”
Her answer to both questions was “no and no. ... There’s just a lot of work to be done” to better understand the condition and when and how to intervene. In the meantime, “don’t treat smoldering melanoma patients” outside of a trial, she said.
“First, do no harm,” Dr. Dispenzieri cautioned in her final slide.
Dr. Lonial said he agreed with many of Dr. Dispenzieri’s points, but disagreed with her conclusion not to treat.
“Everybody can always be critical of randomized trials, but at the end of the day, we now have two randomized phase 3 trials comparing early intervention with no intervention demonstrating a significant delay in developing myeloma. I think it’s time to end the ‘we need more data; we need more trials.’ It’s time for us to take a stand.”
He argued for 2 years of lenalidomide for patients who meet the 2-20-20 high-risk definition, based on the median time people were treated in his trial.
He said he discusses the option “with every smoldering patient [who] walks in to see me” if they aren’t eligible for a trial.
Dr. Lonial mentioned his team is currently pulling together longer-term survival data for their trial.
Hematologist Sagar Lonial, MD, a multiple myeloma specialist and researcher at Emory University, Atlanta, argued for treatment. Hematologist Angela Dispenzieri, MD, also a myeloma researcher and specialist at the Mayo Clinic in Rochester, Minn., took the opposing side, arguing for watchful waiting.
The two experts based their arguments largely on the same two studies, the only randomized trials to tackle the issue to date. While Dr. Dispenzieri focused on their shortcomings, Dr. Lonial focused on their strengths.
In a poll after the debate, about a third of audience members agreed that watchful waiting is the way to go, but about two-thirds favored a personalized approach to smoldering myeloma treatment based on patient risk.
“I’m taking this as a win,” Dr. Lonial said.
Different interpretations of two trials
The first of the two trials recruited from 2007 to 2010 and was conducted in Spain and Portugal. Fifty-seven high-risk patients were randomized to lenalidomide plus dexamethasone (Len-Dex) for up to 2 years; 62 others were randomized to observation.
At 3 years, 70% of observed patients had progressed to multiple myeloma versus only 20% in the Len-Dex group; 82% of Len-Dex patients were alive at data cut-off in 2015 versus 64% of observation patients.
The second, more recent trial, which was led by Dr. Lonial, randomized 92 intermediate or high-risk smoldering myeloma patients to lenalidomide alone for a median of 2 years and 90 others to observation. Three-year progression-free survival (PFS) was 91% in the treatment arm versus 66% with observation. Overall survival data have not yet been reported.
Dr. Dispenzieri acknowledged that the results from Spain and Portugal are impressive. “Treating with Len-Dex gives you a far superior freedom from progression. ... Overall survival was better too.” Results for Len-Dex were “fantastic,” she said.
However, the trial was done before myeloma-defining event criteria existed, so it’s very likely that the treatment arm in the Spanish study included actual myeloma cases, she said.
About 46% of treated patients in Dr. Lonial’s study met the current definition for high risk for progression based on the 2-20-20 rule, which Dr. Dispenzieri helped develop. Although there was an improvement in PFS in the high-risk group, there was no significant improvement for intermediate- and low-risk subjects. Also, more than 80% of observed patients hadn’t progressed by 2 years, and overall survival data are missing.
Meanwhile, treated patients in both trials had more adverse events, including secondary malignancies, and there’s the possibility that early treatment may make patients resistant to treatment later on when they progress to multiple myeloma, although that didn’t seem to happen in the Spanish trial.
“Of course, we want to prevent morbidity, of course we would love to cure the disease,” but “should we treat high-risk smoldering myeloma patients based on overall survival data from a trial of” just 119 “patients that may have been contaminated with actual myeloma” cases? Is it ethical to treat low- and intermediate-risk patients who have only a 50% chance of developing myeloma after 10 years?”
Her answer to both questions was “no and no. ... There’s just a lot of work to be done” to better understand the condition and when and how to intervene. In the meantime, “don’t treat smoldering melanoma patients” outside of a trial, she said.
“First, do no harm,” Dr. Dispenzieri cautioned in her final slide.
Dr. Lonial said he agreed with many of Dr. Dispenzieri’s points, but disagreed with her conclusion not to treat.
“Everybody can always be critical of randomized trials, but at the end of the day, we now have two randomized phase 3 trials comparing early intervention with no intervention demonstrating a significant delay in developing myeloma. I think it’s time to end the ‘we need more data; we need more trials.’ It’s time for us to take a stand.”
He argued for 2 years of lenalidomide for patients who meet the 2-20-20 high-risk definition, based on the median time people were treated in his trial.
He said he discusses the option “with every smoldering patient [who] walks in to see me” if they aren’t eligible for a trial.
Dr. Lonial mentioned his team is currently pulling together longer-term survival data for their trial.
FROM SOHO 2023
Safely skip PET2 after brentuximab in Hodgkin lymphoma?
FROM SOHO 2023
Data from four recent studies indicate that adding frontline brentuximab vedotin to AVD chemotherapy (doxorubicin, vinblastine, dacarbazine) improves outcomes for patients, regardless of PET2 scan results, according to lead investigator Ravand Samaeekia, MD, MSc, from Loma Linda (Calif.) University Medical Center.
These studies, including one conducted by Dr. Samaeekia’s team, provide “evidence for the safe omission of PET2 in treatment regimens that contain brentuximab vedotin,” Dr. Samaeekia, who presented the data, concluded.
Performing an interim PET-CT scan after two cycles of chemotherapy can help oncologists adapt treatment protocols for patients with Hodgkin lymphoma and has become the standard of care for these patients.
However, “there are obviously challenges associated with implementing a PET-guided approach,” said Dr. Samaeekia. Additional PET-CT scans can be costly, time consuming, and increase patients’ risk for toxicities when treatment is escalated based on the scan results.
Given these caveats, Dr. Samaeekia reviewed data exploring whether PET2 has predictive value for patients who receive the anti-CD30 antibody-drug conjugate, brentuximab vedotin, as part of first-line treatment alongside AVD chemotherapy.
Dr. Samaeekia’s team analyzed findings from three trials – ECHELON-1, AHOD1331, and BREACH – which assessed frontline standard of care chemotherapy with or without brentuximab. The team found that incorporating brentuximab into frontline treatment resulted in superior efficacy, and PET2 scans results generally did not change how patients were managed.
In ECHELON-1, 6-year overall survival favored patients with advanced Hodgkin lymphoma who received brentuximab and were PET2 negative (94.9% vs. 90.6%; hazard ratio for death, 0.54) as well as those who were PET2 positive (95% vs. 77%; HR, 0.16). Overall, just over 2% of patients who received the brentuximab regimen switched to an alternative chemotherapy and even fewer did so based on PET2 results.
In AHOD1331, 3-year event-free survival was significantly higher among adolescents and children with Hodgkin lymphoma who received brentuximab – 90.7% for those who had slow-responding lesions and 92.3% for those with rapid-responding lesions. Based on these results, the authors concluded that adding brentuximab “eliminated the predictive value of the interim PET assessment.” The BREACH trial echoed the findings from ECHELON-1 and AHOD1331.
Finally, in a retrospective study of 40 patients treated at Loma Linda with brentuximab vedotin plus AVD, Dr. Samaeekia and colleagues found that 24 were PET2 negative and 12 were PET2 positive. All patients who were PET2 negative remained negative on the end-of-treatment PET, indicating no cancer progression. Of the 12 PET2-positive patients, four (33%) remained PET positive at the end of treatment. Only one patient overall changed regimens following PET2.
Dr. Samaeekia’s team concluded that PET2 scan results “did not have any meaningful impact” on patient management or outcomes.
During the Q&A, Martin Hutchings, MD, PhD, challenged the idea that PET2 can be omitted. Dr. Hutchings, from the Rigshospitalet in Copenhagen, pointed out that 4 of the 12 PET2-positive patients treated at Loma Linda were still PET positive at the end of treatment.
Even so, Dr. Samaeekia explained, PET2 findings did not alter treatment for most patients, noting that doing a PET2 scan may make “us feel better,” but it ultimately doesn’t “make any difference in our management.”
In the AHOD1331 study, “the findings on the interim PET scan were not helpful in the ultimate outcome, whether it was either positive or negative,” added session comoderator Jonathan W. Friedberg, MD, MMSc, director of the James P. Wilmot Cancer Institute at the University of Rochester (N.Y.) Medical Center.
The study by Dr. Samaeekia and colleagues was internally funded. Dr. Samaeekia reports no relevant financial relationships. Dr. Hutchings has previously reported consultancy and research funding from numerous companies. Dr. Friedberg reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM SOHO 2023
Data from four recent studies indicate that adding frontline brentuximab vedotin to AVD chemotherapy (doxorubicin, vinblastine, dacarbazine) improves outcomes for patients, regardless of PET2 scan results, according to lead investigator Ravand Samaeekia, MD, MSc, from Loma Linda (Calif.) University Medical Center.
These studies, including one conducted by Dr. Samaeekia’s team, provide “evidence for the safe omission of PET2 in treatment regimens that contain brentuximab vedotin,” Dr. Samaeekia, who presented the data, concluded.
Performing an interim PET-CT scan after two cycles of chemotherapy can help oncologists adapt treatment protocols for patients with Hodgkin lymphoma and has become the standard of care for these patients.
However, “there are obviously challenges associated with implementing a PET-guided approach,” said Dr. Samaeekia. Additional PET-CT scans can be costly, time consuming, and increase patients’ risk for toxicities when treatment is escalated based on the scan results.
Given these caveats, Dr. Samaeekia reviewed data exploring whether PET2 has predictive value for patients who receive the anti-CD30 antibody-drug conjugate, brentuximab vedotin, as part of first-line treatment alongside AVD chemotherapy.
Dr. Samaeekia’s team analyzed findings from three trials – ECHELON-1, AHOD1331, and BREACH – which assessed frontline standard of care chemotherapy with or without brentuximab. The team found that incorporating brentuximab into frontline treatment resulted in superior efficacy, and PET2 scans results generally did not change how patients were managed.
In ECHELON-1, 6-year overall survival favored patients with advanced Hodgkin lymphoma who received brentuximab and were PET2 negative (94.9% vs. 90.6%; hazard ratio for death, 0.54) as well as those who were PET2 positive (95% vs. 77%; HR, 0.16). Overall, just over 2% of patients who received the brentuximab regimen switched to an alternative chemotherapy and even fewer did so based on PET2 results.
In AHOD1331, 3-year event-free survival was significantly higher among adolescents and children with Hodgkin lymphoma who received brentuximab – 90.7% for those who had slow-responding lesions and 92.3% for those with rapid-responding lesions. Based on these results, the authors concluded that adding brentuximab “eliminated the predictive value of the interim PET assessment.” The BREACH trial echoed the findings from ECHELON-1 and AHOD1331.
Finally, in a retrospective study of 40 patients treated at Loma Linda with brentuximab vedotin plus AVD, Dr. Samaeekia and colleagues found that 24 were PET2 negative and 12 were PET2 positive. All patients who were PET2 negative remained negative on the end-of-treatment PET, indicating no cancer progression. Of the 12 PET2-positive patients, four (33%) remained PET positive at the end of treatment. Only one patient overall changed regimens following PET2.
Dr. Samaeekia’s team concluded that PET2 scan results “did not have any meaningful impact” on patient management or outcomes.
During the Q&A, Martin Hutchings, MD, PhD, challenged the idea that PET2 can be omitted. Dr. Hutchings, from the Rigshospitalet in Copenhagen, pointed out that 4 of the 12 PET2-positive patients treated at Loma Linda were still PET positive at the end of treatment.
Even so, Dr. Samaeekia explained, PET2 findings did not alter treatment for most patients, noting that doing a PET2 scan may make “us feel better,” but it ultimately doesn’t “make any difference in our management.”
In the AHOD1331 study, “the findings on the interim PET scan were not helpful in the ultimate outcome, whether it was either positive or negative,” added session comoderator Jonathan W. Friedberg, MD, MMSc, director of the James P. Wilmot Cancer Institute at the University of Rochester (N.Y.) Medical Center.
The study by Dr. Samaeekia and colleagues was internally funded. Dr. Samaeekia reports no relevant financial relationships. Dr. Hutchings has previously reported consultancy and research funding from numerous companies. Dr. Friedberg reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM SOHO 2023
Data from four recent studies indicate that adding frontline brentuximab vedotin to AVD chemotherapy (doxorubicin, vinblastine, dacarbazine) improves outcomes for patients, regardless of PET2 scan results, according to lead investigator Ravand Samaeekia, MD, MSc, from Loma Linda (Calif.) University Medical Center.
These studies, including one conducted by Dr. Samaeekia’s team, provide “evidence for the safe omission of PET2 in treatment regimens that contain brentuximab vedotin,” Dr. Samaeekia, who presented the data, concluded.
Performing an interim PET-CT scan after two cycles of chemotherapy can help oncologists adapt treatment protocols for patients with Hodgkin lymphoma and has become the standard of care for these patients.
However, “there are obviously challenges associated with implementing a PET-guided approach,” said Dr. Samaeekia. Additional PET-CT scans can be costly, time consuming, and increase patients’ risk for toxicities when treatment is escalated based on the scan results.
Given these caveats, Dr. Samaeekia reviewed data exploring whether PET2 has predictive value for patients who receive the anti-CD30 antibody-drug conjugate, brentuximab vedotin, as part of first-line treatment alongside AVD chemotherapy.
Dr. Samaeekia’s team analyzed findings from three trials – ECHELON-1, AHOD1331, and BREACH – which assessed frontline standard of care chemotherapy with or without brentuximab. The team found that incorporating brentuximab into frontline treatment resulted in superior efficacy, and PET2 scans results generally did not change how patients were managed.
In ECHELON-1, 6-year overall survival favored patients with advanced Hodgkin lymphoma who received brentuximab and were PET2 negative (94.9% vs. 90.6%; hazard ratio for death, 0.54) as well as those who were PET2 positive (95% vs. 77%; HR, 0.16). Overall, just over 2% of patients who received the brentuximab regimen switched to an alternative chemotherapy and even fewer did so based on PET2 results.
In AHOD1331, 3-year event-free survival was significantly higher among adolescents and children with Hodgkin lymphoma who received brentuximab – 90.7% for those who had slow-responding lesions and 92.3% for those with rapid-responding lesions. Based on these results, the authors concluded that adding brentuximab “eliminated the predictive value of the interim PET assessment.” The BREACH trial echoed the findings from ECHELON-1 and AHOD1331.
Finally, in a retrospective study of 40 patients treated at Loma Linda with brentuximab vedotin plus AVD, Dr. Samaeekia and colleagues found that 24 were PET2 negative and 12 were PET2 positive. All patients who were PET2 negative remained negative on the end-of-treatment PET, indicating no cancer progression. Of the 12 PET2-positive patients, four (33%) remained PET positive at the end of treatment. Only one patient overall changed regimens following PET2.
Dr. Samaeekia’s team concluded that PET2 scan results “did not have any meaningful impact” on patient management or outcomes.
During the Q&A, Martin Hutchings, MD, PhD, challenged the idea that PET2 can be omitted. Dr. Hutchings, from the Rigshospitalet in Copenhagen, pointed out that 4 of the 12 PET2-positive patients treated at Loma Linda were still PET positive at the end of treatment.
Even so, Dr. Samaeekia explained, PET2 findings did not alter treatment for most patients, noting that doing a PET2 scan may make “us feel better,” but it ultimately doesn’t “make any difference in our management.”
In the AHOD1331 study, “the findings on the interim PET scan were not helpful in the ultimate outcome, whether it was either positive or negative,” added session comoderator Jonathan W. Friedberg, MD, MMSc, director of the James P. Wilmot Cancer Institute at the University of Rochester (N.Y.) Medical Center.
The study by Dr. Samaeekia and colleagues was internally funded. Dr. Samaeekia reports no relevant financial relationships. Dr. Hutchings has previously reported consultancy and research funding from numerous companies. Dr. Friedberg reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
High rate of subsequent cancers in MCC
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In a cohort of 6,146 patients with a first primary MCC, a total of 725 (11.8%) developed subsequent primary cancers. For solid tumors, the risk was highest for cutaneous melanoma and papillary thyroid carcinoma, while for hematologic cancers, the risk was increased for non-Hodgkin lymphoma.
“Our study does confirm that patients with MCC are at higher risk for developing other cancers,” study author Lisa C. Zaba, MD, PhD, associate professor of dermatology and director of the Merkel cell carcinoma multidisciplinary clinic, Stanford (Calif.) Cancer Center, said in an interview. “MCC is a highly malignant cancer with a 40% recurrence risk.”
Because of this high risk, Dr. Zaba noted that patients with MCC get frequent surveillance with both imaging studies (PET-CT and CT) as well as frequent visits in clinic with MCC experts. “Specifically, a patient with MCC is imaged and seen in clinic every 3-6 months for the first 3 years after diagnosis, and every 6-12 months thereafter for up to 5 years,” she said. “Interestingly, this high level of surveillance may be one reason that we find so many cancers in patients who have been diagnosed with MCC, compared to the general population.”
The study was published online in JAMA Dermatology.
With the death of “Margaritaville” singer Jimmy Buffett, who recently died of MCC 4 years after his diagnosis, this rare, aggressive skin cancer has been put in the spotlight. Survival has been increasing, primarily because of the advent of immunotherapy, and the authors note that it is therefore imperative to better understand the risk of subsequent primary tumors to inform screening and treatment recommendations.
In this cohort study, Dr. Zaba and colleagues identified 6,146 patients from 17 registries of the Surveillance, Epidemiology, and End Results (SEER) Program who had been diagnosed with a first primary cutaneous MCC between 2000 and 2018.
Endpoints were the ratio of observed to expected number of cases of subsequent cancer (Standardized incidence ratio, or SIR) and the excess risk.
Overall, there was an elevated risk of developing a subsequent primary cancer after being diagnosed with MCC (SIR, 1.28; excess risk, 57.25 per 10,000 person-years). This included the risk for all solid tumors including liver (SIR, 1.92; excess risk, 2.77 per 10,000 person-years), pancreas (SIR, 1.65; excess risk, 4.55 per 10,000 person-years), cutaneous melanoma (SIR, 2.36; excess risk, 15.27 per 10,000 person-years), and kidney (SIR, 1.64; excess risk, 3.83 per 10,000 person-years).
There was also a higher risk of developing papillary thyroid carcinoma (PTC) (SIR, 5.26; excess risk, 6.16 per 10,000 person-years).
The risk of developing hematological cancers after MCC was also increased, especially for non-Hodgkin lymphoma (SIR, 2.62; excess risk, 15.48 per 10,000 person-years) and myelodysplastic syndrome (SIR, 2.17; excess risk, 2.73 per 10,000 person-years).
The risk for developing subsequent tumors, including melanoma and non-Hodgkin lymphoma, remained significant for up to 10 years, while the risk for developing PTC and kidney cancers remained for up to 5 years.
“After 3-5 years, when a MCC patient’s risk of MCC recurrence drops below 2%, we do not currently have guidelines in place for additional cancer screening,” Dr. Zaba said. “Regarding patient education, patients with MCC are educated to let us know if they experience any symptoms of cancer between visits, including unintentional weight loss, night sweats, headaches that increasingly worsen, or growing lumps or bumps. These symptoms may occur in a multitude of cancers and not just MCC.”
Weighing in on the study, Jeffrey M. Farma, MD, interim chair, department of surgical oncology at Fox Chase Cancer Center, Philadelphia, noted that MCC is considered to be high risk because of its chances of recurring after surgical resection or spreading to lymph nodes or other areas of the body. “There are approximately 3,000 new cases of melanoma a year in the U.S., and it is 40 times rarer than melanoma,” he said. “Patients are usually diagnosed with Merkel cell carcinoma later in life, and the tumors have been associated with sun exposure and immunosuppression and have also been associated with the polyomavirus.”
That said, however, he emphasized that great strides have been made in treatment. “These tumors are very sensitive to radiation, and we generally treat earlier-stage MCC with a combination of surgery and radiation therapy,” said Dr. Farma. “More recently we have had a lot of success with the use of immunotherapy to treat more advanced MCC.”
Dr. Zaba reported receiving grants from the Kuni Foundation outside the submitted work. No other disclosures were reported. Author Eleni Linos, MD, DrPH, MPH, is supported by grant K24AR075060 from the National Institutes of Health. No other outside funding was reported. Dr. Farma had no disclosures.
.
In a cohort of 6,146 patients with a first primary MCC, a total of 725 (11.8%) developed subsequent primary cancers. For solid tumors, the risk was highest for cutaneous melanoma and papillary thyroid carcinoma, while for hematologic cancers, the risk was increased for non-Hodgkin lymphoma.
“Our study does confirm that patients with MCC are at higher risk for developing other cancers,” study author Lisa C. Zaba, MD, PhD, associate professor of dermatology and director of the Merkel cell carcinoma multidisciplinary clinic, Stanford (Calif.) Cancer Center, said in an interview. “MCC is a highly malignant cancer with a 40% recurrence risk.”
Because of this high risk, Dr. Zaba noted that patients with MCC get frequent surveillance with both imaging studies (PET-CT and CT) as well as frequent visits in clinic with MCC experts. “Specifically, a patient with MCC is imaged and seen in clinic every 3-6 months for the first 3 years after diagnosis, and every 6-12 months thereafter for up to 5 years,” she said. “Interestingly, this high level of surveillance may be one reason that we find so many cancers in patients who have been diagnosed with MCC, compared to the general population.”
The study was published online in JAMA Dermatology.
With the death of “Margaritaville” singer Jimmy Buffett, who recently died of MCC 4 years after his diagnosis, this rare, aggressive skin cancer has been put in the spotlight. Survival has been increasing, primarily because of the advent of immunotherapy, and the authors note that it is therefore imperative to better understand the risk of subsequent primary tumors to inform screening and treatment recommendations.
In this cohort study, Dr. Zaba and colleagues identified 6,146 patients from 17 registries of the Surveillance, Epidemiology, and End Results (SEER) Program who had been diagnosed with a first primary cutaneous MCC between 2000 and 2018.
Endpoints were the ratio of observed to expected number of cases of subsequent cancer (Standardized incidence ratio, or SIR) and the excess risk.
Overall, there was an elevated risk of developing a subsequent primary cancer after being diagnosed with MCC (SIR, 1.28; excess risk, 57.25 per 10,000 person-years). This included the risk for all solid tumors including liver (SIR, 1.92; excess risk, 2.77 per 10,000 person-years), pancreas (SIR, 1.65; excess risk, 4.55 per 10,000 person-years), cutaneous melanoma (SIR, 2.36; excess risk, 15.27 per 10,000 person-years), and kidney (SIR, 1.64; excess risk, 3.83 per 10,000 person-years).
There was also a higher risk of developing papillary thyroid carcinoma (PTC) (SIR, 5.26; excess risk, 6.16 per 10,000 person-years).
The risk of developing hematological cancers after MCC was also increased, especially for non-Hodgkin lymphoma (SIR, 2.62; excess risk, 15.48 per 10,000 person-years) and myelodysplastic syndrome (SIR, 2.17; excess risk, 2.73 per 10,000 person-years).
The risk for developing subsequent tumors, including melanoma and non-Hodgkin lymphoma, remained significant for up to 10 years, while the risk for developing PTC and kidney cancers remained for up to 5 years.
“After 3-5 years, when a MCC patient’s risk of MCC recurrence drops below 2%, we do not currently have guidelines in place for additional cancer screening,” Dr. Zaba said. “Regarding patient education, patients with MCC are educated to let us know if they experience any symptoms of cancer between visits, including unintentional weight loss, night sweats, headaches that increasingly worsen, or growing lumps or bumps. These symptoms may occur in a multitude of cancers and not just MCC.”
Weighing in on the study, Jeffrey M. Farma, MD, interim chair, department of surgical oncology at Fox Chase Cancer Center, Philadelphia, noted that MCC is considered to be high risk because of its chances of recurring after surgical resection or spreading to lymph nodes or other areas of the body. “There are approximately 3,000 new cases of melanoma a year in the U.S., and it is 40 times rarer than melanoma,” he said. “Patients are usually diagnosed with Merkel cell carcinoma later in life, and the tumors have been associated with sun exposure and immunosuppression and have also been associated with the polyomavirus.”
That said, however, he emphasized that great strides have been made in treatment. “These tumors are very sensitive to radiation, and we generally treat earlier-stage MCC with a combination of surgery and radiation therapy,” said Dr. Farma. “More recently we have had a lot of success with the use of immunotherapy to treat more advanced MCC.”
Dr. Zaba reported receiving grants from the Kuni Foundation outside the submitted work. No other disclosures were reported. Author Eleni Linos, MD, DrPH, MPH, is supported by grant K24AR075060 from the National Institutes of Health. No other outside funding was reported. Dr. Farma had no disclosures.
.
In a cohort of 6,146 patients with a first primary MCC, a total of 725 (11.8%) developed subsequent primary cancers. For solid tumors, the risk was highest for cutaneous melanoma and papillary thyroid carcinoma, while for hematologic cancers, the risk was increased for non-Hodgkin lymphoma.
“Our study does confirm that patients with MCC are at higher risk for developing other cancers,” study author Lisa C. Zaba, MD, PhD, associate professor of dermatology and director of the Merkel cell carcinoma multidisciplinary clinic, Stanford (Calif.) Cancer Center, said in an interview. “MCC is a highly malignant cancer with a 40% recurrence risk.”
Because of this high risk, Dr. Zaba noted that patients with MCC get frequent surveillance with both imaging studies (PET-CT and CT) as well as frequent visits in clinic with MCC experts. “Specifically, a patient with MCC is imaged and seen in clinic every 3-6 months for the first 3 years after diagnosis, and every 6-12 months thereafter for up to 5 years,” she said. “Interestingly, this high level of surveillance may be one reason that we find so many cancers in patients who have been diagnosed with MCC, compared to the general population.”
The study was published online in JAMA Dermatology.
With the death of “Margaritaville” singer Jimmy Buffett, who recently died of MCC 4 years after his diagnosis, this rare, aggressive skin cancer has been put in the spotlight. Survival has been increasing, primarily because of the advent of immunotherapy, and the authors note that it is therefore imperative to better understand the risk of subsequent primary tumors to inform screening and treatment recommendations.
In this cohort study, Dr. Zaba and colleagues identified 6,146 patients from 17 registries of the Surveillance, Epidemiology, and End Results (SEER) Program who had been diagnosed with a first primary cutaneous MCC between 2000 and 2018.
Endpoints were the ratio of observed to expected number of cases of subsequent cancer (Standardized incidence ratio, or SIR) and the excess risk.
Overall, there was an elevated risk of developing a subsequent primary cancer after being diagnosed with MCC (SIR, 1.28; excess risk, 57.25 per 10,000 person-years). This included the risk for all solid tumors including liver (SIR, 1.92; excess risk, 2.77 per 10,000 person-years), pancreas (SIR, 1.65; excess risk, 4.55 per 10,000 person-years), cutaneous melanoma (SIR, 2.36; excess risk, 15.27 per 10,000 person-years), and kidney (SIR, 1.64; excess risk, 3.83 per 10,000 person-years).
There was also a higher risk of developing papillary thyroid carcinoma (PTC) (SIR, 5.26; excess risk, 6.16 per 10,000 person-years).
The risk of developing hematological cancers after MCC was also increased, especially for non-Hodgkin lymphoma (SIR, 2.62; excess risk, 15.48 per 10,000 person-years) and myelodysplastic syndrome (SIR, 2.17; excess risk, 2.73 per 10,000 person-years).
The risk for developing subsequent tumors, including melanoma and non-Hodgkin lymphoma, remained significant for up to 10 years, while the risk for developing PTC and kidney cancers remained for up to 5 years.
“After 3-5 years, when a MCC patient’s risk of MCC recurrence drops below 2%, we do not currently have guidelines in place for additional cancer screening,” Dr. Zaba said. “Regarding patient education, patients with MCC are educated to let us know if they experience any symptoms of cancer between visits, including unintentional weight loss, night sweats, headaches that increasingly worsen, or growing lumps or bumps. These symptoms may occur in a multitude of cancers and not just MCC.”
Weighing in on the study, Jeffrey M. Farma, MD, interim chair, department of surgical oncology at Fox Chase Cancer Center, Philadelphia, noted that MCC is considered to be high risk because of its chances of recurring after surgical resection or spreading to lymph nodes or other areas of the body. “There are approximately 3,000 new cases of melanoma a year in the U.S., and it is 40 times rarer than melanoma,” he said. “Patients are usually diagnosed with Merkel cell carcinoma later in life, and the tumors have been associated with sun exposure and immunosuppression and have also been associated with the polyomavirus.”
That said, however, he emphasized that great strides have been made in treatment. “These tumors are very sensitive to radiation, and we generally treat earlier-stage MCC with a combination of surgery and radiation therapy,” said Dr. Farma. “More recently we have had a lot of success with the use of immunotherapy to treat more advanced MCC.”
Dr. Zaba reported receiving grants from the Kuni Foundation outside the submitted work. No other disclosures were reported. Author Eleni Linos, MD, DrPH, MPH, is supported by grant K24AR075060 from the National Institutes of Health. No other outside funding was reported. Dr. Farma had no disclosures.
FROM JAMA DERMATOLOGY
FDA approves motixafortide for stem cell mobilization in myeloma
The success of autologous stem cell transplantation (ASCT) depends on adequate mobilization of stem cells during the treatment process. Collection of a sufficient number of stem cells to perform two transplantations is recommended. However, in up to 47% of patients, collecting target numbers of hematopoietic stem cells for ASCT after one apheresis session remains a challenge, BioLineRx explained in a press release today, announcing the approval.
The goal of combining motixafortide with filgrastim is to mobilize stem cells more reliably than filgrastim can alone, with fewer days of apheresis sessions and fewer doses of filgrastim.
“We believe [motixafortide] will play a critical role in addressing unmet needs and introduce a new treatment paradigm for” patients with multiple myeloma, CEO Philip Serlin said in the release.
The drug approval was based on the GENESIS trial, which randomized 122 patients to either motixafortide plus filgrastim or placebo plus filgrastim.
BioLineRx said the trial included patients considered representative of the typical multiple myeloma population undergoing ASCT, with a median age of 63 years and with about 70% of patients in both arms of the trial receiving lenalidomide-containing induction therapy.
Motixafortide plus filgrastim enabled 67.5% of patients to achieve the stem cell collection goal of 6 million or more CD34+ cells/kg within two apheresis sessions, versus 9.5% of patients receiving the placebo plus filgrastim regimen. Additionally, 92.5% of patients reached the stem cell collection goal in up to two apheresis sessions in the motixafortide arm and 21.4% in the placebo arm.
However, “the data are descriptive and were not statistically powered nor prespecified. The information should be cautiously interpreted,” the company said.
Serious adverse reactions occurred in 5.4% of patients in the motixafortide arm, including vomiting, injection-site reaction, hypersensitivity reaction, injection-site cellulitis, hypokalemia, and hypoxia. The most common adverse reactions, occurring in more than 20% of patients, were injection site reactions (pain, erythema, and pruritus), pruritus, flushing, and back pain.
Labeling for the subcutaneous injection is available online.
A version of this article first appeared on Medscape.com.
The success of autologous stem cell transplantation (ASCT) depends on adequate mobilization of stem cells during the treatment process. Collection of a sufficient number of stem cells to perform two transplantations is recommended. However, in up to 47% of patients, collecting target numbers of hematopoietic stem cells for ASCT after one apheresis session remains a challenge, BioLineRx explained in a press release today, announcing the approval.
The goal of combining motixafortide with filgrastim is to mobilize stem cells more reliably than filgrastim can alone, with fewer days of apheresis sessions and fewer doses of filgrastim.
“We believe [motixafortide] will play a critical role in addressing unmet needs and introduce a new treatment paradigm for” patients with multiple myeloma, CEO Philip Serlin said in the release.
The drug approval was based on the GENESIS trial, which randomized 122 patients to either motixafortide plus filgrastim or placebo plus filgrastim.
BioLineRx said the trial included patients considered representative of the typical multiple myeloma population undergoing ASCT, with a median age of 63 years and with about 70% of patients in both arms of the trial receiving lenalidomide-containing induction therapy.
Motixafortide plus filgrastim enabled 67.5% of patients to achieve the stem cell collection goal of 6 million or more CD34+ cells/kg within two apheresis sessions, versus 9.5% of patients receiving the placebo plus filgrastim regimen. Additionally, 92.5% of patients reached the stem cell collection goal in up to two apheresis sessions in the motixafortide arm and 21.4% in the placebo arm.
However, “the data are descriptive and were not statistically powered nor prespecified. The information should be cautiously interpreted,” the company said.
Serious adverse reactions occurred in 5.4% of patients in the motixafortide arm, including vomiting, injection-site reaction, hypersensitivity reaction, injection-site cellulitis, hypokalemia, and hypoxia. The most common adverse reactions, occurring in more than 20% of patients, were injection site reactions (pain, erythema, and pruritus), pruritus, flushing, and back pain.
Labeling for the subcutaneous injection is available online.
A version of this article first appeared on Medscape.com.
The success of autologous stem cell transplantation (ASCT) depends on adequate mobilization of stem cells during the treatment process. Collection of a sufficient number of stem cells to perform two transplantations is recommended. However, in up to 47% of patients, collecting target numbers of hematopoietic stem cells for ASCT after one apheresis session remains a challenge, BioLineRx explained in a press release today, announcing the approval.
The goal of combining motixafortide with filgrastim is to mobilize stem cells more reliably than filgrastim can alone, with fewer days of apheresis sessions and fewer doses of filgrastim.
“We believe [motixafortide] will play a critical role in addressing unmet needs and introduce a new treatment paradigm for” patients with multiple myeloma, CEO Philip Serlin said in the release.
The drug approval was based on the GENESIS trial, which randomized 122 patients to either motixafortide plus filgrastim or placebo plus filgrastim.
BioLineRx said the trial included patients considered representative of the typical multiple myeloma population undergoing ASCT, with a median age of 63 years and with about 70% of patients in both arms of the trial receiving lenalidomide-containing induction therapy.
Motixafortide plus filgrastim enabled 67.5% of patients to achieve the stem cell collection goal of 6 million or more CD34+ cells/kg within two apheresis sessions, versus 9.5% of patients receiving the placebo plus filgrastim regimen. Additionally, 92.5% of patients reached the stem cell collection goal in up to two apheresis sessions in the motixafortide arm and 21.4% in the placebo arm.
However, “the data are descriptive and were not statistically powered nor prespecified. The information should be cautiously interpreted,” the company said.
Serious adverse reactions occurred in 5.4% of patients in the motixafortide arm, including vomiting, injection-site reaction, hypersensitivity reaction, injection-site cellulitis, hypokalemia, and hypoxia. The most common adverse reactions, occurring in more than 20% of patients, were injection site reactions (pain, erythema, and pruritus), pruritus, flushing, and back pain.
Labeling for the subcutaneous injection is available online.
A version of this article first appeared on Medscape.com.
Is additional treatment needed, pretransplant, for r/r AML?
This critically important question was debated at the annual meeting of the Society of Hematologic Oncology, held in Houston and online.
Johannes Schetelig, MD, argued in favor of proceeding to transplant, even without a complete remission.
“In the past, I’ve told many patients with relapsed or refractory AML that we do need to induce a [complete remission] prior to transplantation,” said Dr. Schetelig, from the Clinical Trials Unit at DKMS in Dresden, Germany. “But is it true?”
According to findings from a recent randomized trial, it may not be. The trial, led by Dr. Schetelig, found that patients with AML who received immediate allogeneic transplant without first having achieved a complete response following induction therapy did just as well as those who received intensive salvage induction therapy to establish remission before transplant.
If this finding holds, it “completely upends” how experts have traditionally approached patients with AML, Mikkael A. Sekeres, MD, of the University of Miami said at a conference press briefing last year.
The phase 3 ASAP trial, presented at last year’s American Society of Hematology meeting, included patients with AML who had had a poor response or who had experienced a relapse after first induction therapy. Patients were randomly assigned to a remission-induction strategy prior to allogeneic stem cell transplant (alloHCT) or a disease-control approach of watchful waiting followed by sequential conditioning and alloHCT. The primary endpoint was treatment success, defined as a complete response at day 56 following alloHCT.
In an intention-to-treat analysis, 83.5% of patients in the disease-control group and 81% in the remission-induction group achieved treatment success. Similarly, in the per-protocol analysis, 84.1% and 81.3%, respectively, achieved a complete response at day 56 after alloHCT. After a median follow-up of 4 years, there were no differences in leukemia-free survival or overall survival between the two groups.
Another advantage to forgoing an intensive salvage induction regimen: Patients in the disease-control arm experienced significantly fewer severe adverse events (23% vs. 64% in the remission induction arm) and spent a mean of 27 fewer days in the hospital prior to transplantation.
At last year’s press briefing, Dr. Schetelig said his team did not expect that a complete response on day 56 after transplantation would translate into “equal long-term benefit” for these groups. “This is what I was really astonished about,” he said.
Delving further into the findings, Dr. Schetelig explained that in the remission-induction arm patients who had had a complete response prior to transplantation demonstrated significantly better overall survival at 4 years than those who had not had a complete response at that point: 60% vs. 40%.
The study also revealed that in the disease-control arm, for patients under watchful waiting who did not need low-dose cytarabine and mitoxantrone for disease control, overall survival outcomes were similar to those of patients in the remission-induction arm who achieved a complete response.
These findings suggest that patients who can be bridged with watchful waiting may have a more favorable disease biology, and chemosensitivity could just be a biomarker for disease biology. In other words, “AML biology matters for transplant outcome and not tumor load,” Dr. Schetelig explained.
A recent study that found that having minimal residual disease (MRD) prior to transplant “had no independent effect on leukemia-free survival” supports this idea, he added.
Overall, Dr. Schetelig concluded that data from the ASAP trial suggest that watchful waiting prior to alloHCT represents “an alternative” for some patients.
Counterpoint: Aim for complete remission
Ronald B. Walter, MD, PhD, argued the counterpoint: that residual disease before transplantation is associated with worse posttransplant outcomes and represents a meaningful pretransplant therapeutic target.
The goal of intensifying treatment for patients with residual disease is to erase disease vestiges prior to transplantation.
“The idea is that by doing so you might optimize the benefit-to-risk ratio and ultimately improve outcomes,” said Dr. Walter, of the translational science and therapeutics division at the Fred Hutchinson Cancer Research Center in Seattle.
Several reports support this view that patients who are MRD negative at the time of transplant have significantly better survival outcomes than patients with residual disease who undergo transplant.
A 2016 study from Dr. Walter and colleagues at Fred Hutchinson, for instance, found that 3-year overall survival was significantly higher among patients with no MRD who underwent myeloablative alloHCT: 73% vs. 26% of those in MRD-positive morphologic remission and 23% of patients with active AML.
Another study, published the year before by a different research team, also revealed that “adult patients with AML in morphologic [complete remission] but with detectable MRD who undergo alloHCT have poor outcomes, which approximates those who undergo transplantation with active disease,” the authors of the 2015 study wrote in a commentary highlighting findings from both studies.
Still, providing intensive therapy prior to transplant comes with drawbacks, Dr. Walter noted. These downsides include potential toxicity from more intense therapy, which may prevent further therapy with curative intent, as well as the possibility that deintensifying therapy could lead to difficult-to-treat relapse.
It may, however, be possible to reduce the intensity of therapy before transplant and still achieve good outcomes after transplant, though the data remain mixed.
One trial found that a reduced-intensity conditioning regimen was associated with a greater risk of relapse post transplant and worse overall survival, compared with standard myeloablative conditioning.
However, another recent trial in which patients with AML or high-risk myelodysplastic syndrome were randomly assigned to either a reduced-intensity conditioning regimen or an intensified version of that regimen prior to transplant demonstrated no difference in relapse rates and overall survival, regardless of patients’ MRD status prior to transplant.
“To me, it’s still key to go into transplant with as little disease as possible,” Dr. Walter said. How much value there is in targeted treatment to further reduce disease burden prior to transplant “will really require further careful study,” he said.
The ASAP trial was sponsored by DKMS. Dr. Schetelig has received honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Dr. Walter reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
This critically important question was debated at the annual meeting of the Society of Hematologic Oncology, held in Houston and online.
Johannes Schetelig, MD, argued in favor of proceeding to transplant, even without a complete remission.
“In the past, I’ve told many patients with relapsed or refractory AML that we do need to induce a [complete remission] prior to transplantation,” said Dr. Schetelig, from the Clinical Trials Unit at DKMS in Dresden, Germany. “But is it true?”
According to findings from a recent randomized trial, it may not be. The trial, led by Dr. Schetelig, found that patients with AML who received immediate allogeneic transplant without first having achieved a complete response following induction therapy did just as well as those who received intensive salvage induction therapy to establish remission before transplant.
If this finding holds, it “completely upends” how experts have traditionally approached patients with AML, Mikkael A. Sekeres, MD, of the University of Miami said at a conference press briefing last year.
The phase 3 ASAP trial, presented at last year’s American Society of Hematology meeting, included patients with AML who had had a poor response or who had experienced a relapse after first induction therapy. Patients were randomly assigned to a remission-induction strategy prior to allogeneic stem cell transplant (alloHCT) or a disease-control approach of watchful waiting followed by sequential conditioning and alloHCT. The primary endpoint was treatment success, defined as a complete response at day 56 following alloHCT.
In an intention-to-treat analysis, 83.5% of patients in the disease-control group and 81% in the remission-induction group achieved treatment success. Similarly, in the per-protocol analysis, 84.1% and 81.3%, respectively, achieved a complete response at day 56 after alloHCT. After a median follow-up of 4 years, there were no differences in leukemia-free survival or overall survival between the two groups.
Another advantage to forgoing an intensive salvage induction regimen: Patients in the disease-control arm experienced significantly fewer severe adverse events (23% vs. 64% in the remission induction arm) and spent a mean of 27 fewer days in the hospital prior to transplantation.
At last year’s press briefing, Dr. Schetelig said his team did not expect that a complete response on day 56 after transplantation would translate into “equal long-term benefit” for these groups. “This is what I was really astonished about,” he said.
Delving further into the findings, Dr. Schetelig explained that in the remission-induction arm patients who had had a complete response prior to transplantation demonstrated significantly better overall survival at 4 years than those who had not had a complete response at that point: 60% vs. 40%.
The study also revealed that in the disease-control arm, for patients under watchful waiting who did not need low-dose cytarabine and mitoxantrone for disease control, overall survival outcomes were similar to those of patients in the remission-induction arm who achieved a complete response.
These findings suggest that patients who can be bridged with watchful waiting may have a more favorable disease biology, and chemosensitivity could just be a biomarker for disease biology. In other words, “AML biology matters for transplant outcome and not tumor load,” Dr. Schetelig explained.
A recent study that found that having minimal residual disease (MRD) prior to transplant “had no independent effect on leukemia-free survival” supports this idea, he added.
Overall, Dr. Schetelig concluded that data from the ASAP trial suggest that watchful waiting prior to alloHCT represents “an alternative” for some patients.
Counterpoint: Aim for complete remission
Ronald B. Walter, MD, PhD, argued the counterpoint: that residual disease before transplantation is associated with worse posttransplant outcomes and represents a meaningful pretransplant therapeutic target.
The goal of intensifying treatment for patients with residual disease is to erase disease vestiges prior to transplantation.
“The idea is that by doing so you might optimize the benefit-to-risk ratio and ultimately improve outcomes,” said Dr. Walter, of the translational science and therapeutics division at the Fred Hutchinson Cancer Research Center in Seattle.
Several reports support this view that patients who are MRD negative at the time of transplant have significantly better survival outcomes than patients with residual disease who undergo transplant.
A 2016 study from Dr. Walter and colleagues at Fred Hutchinson, for instance, found that 3-year overall survival was significantly higher among patients with no MRD who underwent myeloablative alloHCT: 73% vs. 26% of those in MRD-positive morphologic remission and 23% of patients with active AML.
Another study, published the year before by a different research team, also revealed that “adult patients with AML in morphologic [complete remission] but with detectable MRD who undergo alloHCT have poor outcomes, which approximates those who undergo transplantation with active disease,” the authors of the 2015 study wrote in a commentary highlighting findings from both studies.
Still, providing intensive therapy prior to transplant comes with drawbacks, Dr. Walter noted. These downsides include potential toxicity from more intense therapy, which may prevent further therapy with curative intent, as well as the possibility that deintensifying therapy could lead to difficult-to-treat relapse.
It may, however, be possible to reduce the intensity of therapy before transplant and still achieve good outcomes after transplant, though the data remain mixed.
One trial found that a reduced-intensity conditioning regimen was associated with a greater risk of relapse post transplant and worse overall survival, compared with standard myeloablative conditioning.
However, another recent trial in which patients with AML or high-risk myelodysplastic syndrome were randomly assigned to either a reduced-intensity conditioning regimen or an intensified version of that regimen prior to transplant demonstrated no difference in relapse rates and overall survival, regardless of patients’ MRD status prior to transplant.
“To me, it’s still key to go into transplant with as little disease as possible,” Dr. Walter said. How much value there is in targeted treatment to further reduce disease burden prior to transplant “will really require further careful study,” he said.
The ASAP trial was sponsored by DKMS. Dr. Schetelig has received honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Dr. Walter reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
This critically important question was debated at the annual meeting of the Society of Hematologic Oncology, held in Houston and online.
Johannes Schetelig, MD, argued in favor of proceeding to transplant, even without a complete remission.
“In the past, I’ve told many patients with relapsed or refractory AML that we do need to induce a [complete remission] prior to transplantation,” said Dr. Schetelig, from the Clinical Trials Unit at DKMS in Dresden, Germany. “But is it true?”
According to findings from a recent randomized trial, it may not be. The trial, led by Dr. Schetelig, found that patients with AML who received immediate allogeneic transplant without first having achieved a complete response following induction therapy did just as well as those who received intensive salvage induction therapy to establish remission before transplant.
If this finding holds, it “completely upends” how experts have traditionally approached patients with AML, Mikkael A. Sekeres, MD, of the University of Miami said at a conference press briefing last year.
The phase 3 ASAP trial, presented at last year’s American Society of Hematology meeting, included patients with AML who had had a poor response or who had experienced a relapse after first induction therapy. Patients were randomly assigned to a remission-induction strategy prior to allogeneic stem cell transplant (alloHCT) or a disease-control approach of watchful waiting followed by sequential conditioning and alloHCT. The primary endpoint was treatment success, defined as a complete response at day 56 following alloHCT.
In an intention-to-treat analysis, 83.5% of patients in the disease-control group and 81% in the remission-induction group achieved treatment success. Similarly, in the per-protocol analysis, 84.1% and 81.3%, respectively, achieved a complete response at day 56 after alloHCT. After a median follow-up of 4 years, there were no differences in leukemia-free survival or overall survival between the two groups.
Another advantage to forgoing an intensive salvage induction regimen: Patients in the disease-control arm experienced significantly fewer severe adverse events (23% vs. 64% in the remission induction arm) and spent a mean of 27 fewer days in the hospital prior to transplantation.
At last year’s press briefing, Dr. Schetelig said his team did not expect that a complete response on day 56 after transplantation would translate into “equal long-term benefit” for these groups. “This is what I was really astonished about,” he said.
Delving further into the findings, Dr. Schetelig explained that in the remission-induction arm patients who had had a complete response prior to transplantation demonstrated significantly better overall survival at 4 years than those who had not had a complete response at that point: 60% vs. 40%.
The study also revealed that in the disease-control arm, for patients under watchful waiting who did not need low-dose cytarabine and mitoxantrone for disease control, overall survival outcomes were similar to those of patients in the remission-induction arm who achieved a complete response.
These findings suggest that patients who can be bridged with watchful waiting may have a more favorable disease biology, and chemosensitivity could just be a biomarker for disease biology. In other words, “AML biology matters for transplant outcome and not tumor load,” Dr. Schetelig explained.
A recent study that found that having minimal residual disease (MRD) prior to transplant “had no independent effect on leukemia-free survival” supports this idea, he added.
Overall, Dr. Schetelig concluded that data from the ASAP trial suggest that watchful waiting prior to alloHCT represents “an alternative” for some patients.
Counterpoint: Aim for complete remission
Ronald B. Walter, MD, PhD, argued the counterpoint: that residual disease before transplantation is associated with worse posttransplant outcomes and represents a meaningful pretransplant therapeutic target.
The goal of intensifying treatment for patients with residual disease is to erase disease vestiges prior to transplantation.
“The idea is that by doing so you might optimize the benefit-to-risk ratio and ultimately improve outcomes,” said Dr. Walter, of the translational science and therapeutics division at the Fred Hutchinson Cancer Research Center in Seattle.
Several reports support this view that patients who are MRD negative at the time of transplant have significantly better survival outcomes than patients with residual disease who undergo transplant.
A 2016 study from Dr. Walter and colleagues at Fred Hutchinson, for instance, found that 3-year overall survival was significantly higher among patients with no MRD who underwent myeloablative alloHCT: 73% vs. 26% of those in MRD-positive morphologic remission and 23% of patients with active AML.
Another study, published the year before by a different research team, also revealed that “adult patients with AML in morphologic [complete remission] but with detectable MRD who undergo alloHCT have poor outcomes, which approximates those who undergo transplantation with active disease,” the authors of the 2015 study wrote in a commentary highlighting findings from both studies.
Still, providing intensive therapy prior to transplant comes with drawbacks, Dr. Walter noted. These downsides include potential toxicity from more intense therapy, which may prevent further therapy with curative intent, as well as the possibility that deintensifying therapy could lead to difficult-to-treat relapse.
It may, however, be possible to reduce the intensity of therapy before transplant and still achieve good outcomes after transplant, though the data remain mixed.
One trial found that a reduced-intensity conditioning regimen was associated with a greater risk of relapse post transplant and worse overall survival, compared with standard myeloablative conditioning.
However, another recent trial in which patients with AML or high-risk myelodysplastic syndrome were randomly assigned to either a reduced-intensity conditioning regimen or an intensified version of that regimen prior to transplant demonstrated no difference in relapse rates and overall survival, regardless of patients’ MRD status prior to transplant.
“To me, it’s still key to go into transplant with as little disease as possible,” Dr. Walter said. How much value there is in targeted treatment to further reduce disease burden prior to transplant “will really require further careful study,” he said.
The ASAP trial was sponsored by DKMS. Dr. Schetelig has received honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Dr. Walter reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM SOHO 2023
Seeking help for burnout may be a gamble for doctors
By the end of 2021, Anuj Peddada, MD, had hit a wall. He couldn’t sleep, couldn’t concentrate, erupted in anger, and felt isolated personally and professionally. To temper pandemic-driven pressures, the Colorado radiation oncologist took an 8-week stress management and resiliency course, but the feelings kept creeping back.
Still, Dr. Peddada, in his own private practice, pushed through, working 60-hour weeks and carrying the workload of two physicians. It wasn’t until he caught himself making uncharacteristic medical errors, including radiation planning for the wrong site, that he knew he needed help – and possibly a temporary break from medicine.
There was just one hitch: He was closing his private practice to start a new in-house job with Centura Health, the Colorado Springs hospital he’d contracted with for over 20 years.
Given the long-standing relationship – Dr. Peddada’s image graced some of the company’s marketing billboards – he expected Centura would understand when, on his doctor’s recommendation, he requested a short-term medical leave that would delay his start date by 1 month.
Instead, Centura abruptly rescinded the employment offer, leaving Dr. Peddada jobless and with no recourse but to sue.
“I was blindsided. The hospital had a physician resiliency program that claimed to encourage physicians to seek help, [so] I thought they would be completely supportive and understanding,” Dr. Peddada said.
He told this news organization that he was naive to have been so honest with the hospital he’d long served as a contractor, including the decade-plus he›d spent directing its radiation oncology department.
“It is exceedingly painful to see hospital leadership use me in their advertisement[s] ... trying to profit off my reputation and work after devastating my career.”
The lawsuit Dr. Peddada filed in July in Colorado federal district court may offer a rare glimpse of the potential career ramifications of seeking help for physician burnout. Despite employers’ oft-stated support for physician wellness, Dr. Peddada’s experience may serve as a cautionary tale for doctors who are open about their struggles.
Centura Health did not respond to requests for comment. In court documents, the health system’s attorneys asked for more time to respond to Dr. Peddada’s complaint.
A plea for help
In the complaint, Dr. Peddada and his attorneys claim that Centura violated the state’s Anti-Discrimination Act and the Americans with Disabilities Act (ADA) when it failed to offer reasonable accommodations after he began experiencing “physiological and psychological symptoms corresponding to burnout.”
Since 1999, Dr. Peddada had contracted exclusively with Centura to provide oncology services at its hospital, Penrose Cancer Center, and began covering a second Centura location in 2021. As medical director of Penrose’s radiation oncology department, he helped establish a community nurse navigator program and accounted for 75% of Centura’s radiation oncology referrals, according to the complaint.
But when his symptoms and fear for the safety of his patients became unbearable, Dr. Peddada requested an urgent evaluation from his primary care physician, who diagnosed him with “physician burnout” and recommended medical leave.
Shortly after presenting the leave request to Centura, rumors began circulating that he was having a “nervous breakdown,” the complaint noted. Dr. Peddada worried that perhaps his private health information was being shared with hospital employees.
After meeting with the hospital’s head of physician resiliency and agreeing to undergo a peer review evaluation by the Colorado Physician Health Program, which would decide the reinstatement timeline and if further therapy was necessary, Dr. Peddada was assured his leave would be approved.
Five days later, his job offer was revoked.
In an email from hospital leadership, the oncologist was informed that he had “declined employment” by failing to sign a revised employment contract sent to him 2 weeks prior when he was out of state on a preapproved vacation, according to the lawsuit.
The lawsuit alleges that Dr. Peddada was wrongfully discharged due to his disability after Centura “exploited [his] extensive patient base, referral network, and reputation to generate growth and profit.”
Colorado employment law attorney Deborah Yim, Esq., who is not involved in Peddada’s case, told this news organization that the ADA requires employers to provide reasonable accommodations for physical or mental impairments that substantially limit at least one major life activity, except when the request imposes an undue hardship on the employer.
“Depression and related mental health conditions would qualify, depending on the circumstances, and courts have certainly found them to be qualifying disabilities entitled to ADA protection in the past,” she said.
Not all employers are receptive to doctors’ needs, says the leadership team at Physicians Just Equity, an organization providing peer support to doctors experiencing workplace conflicts like discrimination and retaliation. They say that Dr. Peddada’s experience, where disclosing burnout results in being “ostracized, penalized, and ultimately ousted,” is the rule rather than the exception.
“Dr. Peddada’s case represents the unfortunate reality faced by many physicians in today’s clinical landscape,” the organization’s board of directors said in a written statement. “The imbalance of unreasonable professional demands, the lack of autonomy, moral injury, and disintegrating practice rewards is unsustainable for the medical professional.”
“Retaliation by employers after speaking up against this imbalance [and] requesting support and time to rejuvenate is a grave failure of health care systems that prioritize the business of delivering health care over the health, well-being, and satisfaction of their most valuable resource – the physician,” the board added in their statement.
Dr. Peddada has since closed his private practice and works as an independent contractor and consultant, his attorney, Iris Halpern, JD, said in an interview. She says Centura could have honored the accommodation request or suggested another option that met his needs, but “not only were they unsupportive, they terminated him.”
Ms. Yim says the parties will have opportunities to reach a settlement and resolve the dispute as the case works through the court system. Otherwise, Dr. Peddada and Centura may eventually head to trial.
Current state of physician burnout
The state of physician burnout is certainly a concerning one. More than half (53%) of physicians responding to this year’s Medscape Physician Burnout & Depression Report said they are burned out. Nearly one-quarter reported feeling depressed. Some of the top reasons they cited were too many bureaucratic tasks (61%), too many work hours (37%), and lack of autonomy (31%).
A 2022 study by the Mayo Clinic found a substantial increase in physician burnout in the first 2 years of the pandemic, with doctors reporting rising emotional exhaustion and depersonalization.
Although burnout affects many physicians and is a priority focus of the National Academy of Medicine’s plan to restore workforce well-being, admitting it is often seen as taboo and can imperil a doctor’s career. In the Medscape report, for example, 39% of physicians said they would not even consider professional treatment for burnout, with many commenting that they would just deal with it themselves.
“Many physicians are frightened to take time out for self-care because [they] fear losing their job, being stigmatized, and potentially ending their careers,” said Dr. Peddada, adding that physicians are commonly asked questions about their mental health when applying for hospital privileges. He says this dynamic forces them to choose between getting help or ignoring their true feelings, leading to poor quality of care and patient safety risks.
Medical licensing boards probe physicians’ mental health, too. As part of its #FightingForDocs campaign, the American Medical Association hopes to remove the stigma around burnout and depression and advocates for licensing boards to revise questions that may discourage physicians from seeking assistance. The AMA recommends that physicians only disclose current physical or mental conditions affecting their ability to practice.
Pringl Miller, MD, founder and executive director of Physician Just Equity, told Medscape that improving physician wellness requires structural change.
“Physicians (who) experience burnout without the proper accommodations run the risk of personal harm, because most physicians will prioritize the health and well-being of their patients over themselves ... [resulting in] suboptimal and unsafe patient care,” she said.
Helping doctors regain a sense of purpose
One change involves reframing how the health care industry thinks about and approaches burnout, says Steven Siegel, MD, chief mental health and wellness officer with Keck Medicine of USC. He told this news organization that these discussions should enhance the physician’s sense of purpose.
“Some people treat burnout as a concrete disorder like cancer, instead of saying, ‘I’m feeling exhausted, demoralized, and don’t enjoy my job anymore. What can we do to restore my enthusiasm for work?’ ”
Dr. Siegel recognizes that these issues existed before the pandemic and have only worsened as physicians feel less connected to and satisfied with their profession – a byproduct, he says, of the commercialization of medicine.
“We’ve moved from practices to systems, then from small to large systems, where it seems the path to survival is cutting costs and increasing margins, even among nonprofits.”
The road ahead
Making headway on these problems will take time. Last year, Keck Medicine received a $2 million grant to launch a 3-year randomized clinical trial to help reconnect physicians and other clinicians with their work. Dr. Siegel says the trial may serve as a national pilot program and will eventually grow to include 400 volunteers.
The trial will investigate the effectiveness of three possible interventions: (1) teaching people how to regulate their internal narratives and emotions through techniques like cognitive behavioral therapy and acceptance and commitment therapy; (2) providing customized EHR training to reduce the burden of navigating the system; and (3) allowing physicians to weigh in on workflow changes.
“We put physicians on teams that make the decisions about workflows,” said Dr. Siegel. The arrangement can give people the agency they desire and help them understand why an idea might not be plausible, which enriches future suggestions and discussions, he says.
A version of this article first appeared on Medscape.com.
By the end of 2021, Anuj Peddada, MD, had hit a wall. He couldn’t sleep, couldn’t concentrate, erupted in anger, and felt isolated personally and professionally. To temper pandemic-driven pressures, the Colorado radiation oncologist took an 8-week stress management and resiliency course, but the feelings kept creeping back.
Still, Dr. Peddada, in his own private practice, pushed through, working 60-hour weeks and carrying the workload of two physicians. It wasn’t until he caught himself making uncharacteristic medical errors, including radiation planning for the wrong site, that he knew he needed help – and possibly a temporary break from medicine.
There was just one hitch: He was closing his private practice to start a new in-house job with Centura Health, the Colorado Springs hospital he’d contracted with for over 20 years.
Given the long-standing relationship – Dr. Peddada’s image graced some of the company’s marketing billboards – he expected Centura would understand when, on his doctor’s recommendation, he requested a short-term medical leave that would delay his start date by 1 month.
Instead, Centura abruptly rescinded the employment offer, leaving Dr. Peddada jobless and with no recourse but to sue.
“I was blindsided. The hospital had a physician resiliency program that claimed to encourage physicians to seek help, [so] I thought they would be completely supportive and understanding,” Dr. Peddada said.
He told this news organization that he was naive to have been so honest with the hospital he’d long served as a contractor, including the decade-plus he›d spent directing its radiation oncology department.
“It is exceedingly painful to see hospital leadership use me in their advertisement[s] ... trying to profit off my reputation and work after devastating my career.”
The lawsuit Dr. Peddada filed in July in Colorado federal district court may offer a rare glimpse of the potential career ramifications of seeking help for physician burnout. Despite employers’ oft-stated support for physician wellness, Dr. Peddada’s experience may serve as a cautionary tale for doctors who are open about their struggles.
Centura Health did not respond to requests for comment. In court documents, the health system’s attorneys asked for more time to respond to Dr. Peddada’s complaint.
A plea for help
In the complaint, Dr. Peddada and his attorneys claim that Centura violated the state’s Anti-Discrimination Act and the Americans with Disabilities Act (ADA) when it failed to offer reasonable accommodations after he began experiencing “physiological and psychological symptoms corresponding to burnout.”
Since 1999, Dr. Peddada had contracted exclusively with Centura to provide oncology services at its hospital, Penrose Cancer Center, and began covering a second Centura location in 2021. As medical director of Penrose’s radiation oncology department, he helped establish a community nurse navigator program and accounted for 75% of Centura’s radiation oncology referrals, according to the complaint.
But when his symptoms and fear for the safety of his patients became unbearable, Dr. Peddada requested an urgent evaluation from his primary care physician, who diagnosed him with “physician burnout” and recommended medical leave.
Shortly after presenting the leave request to Centura, rumors began circulating that he was having a “nervous breakdown,” the complaint noted. Dr. Peddada worried that perhaps his private health information was being shared with hospital employees.
After meeting with the hospital’s head of physician resiliency and agreeing to undergo a peer review evaluation by the Colorado Physician Health Program, which would decide the reinstatement timeline and if further therapy was necessary, Dr. Peddada was assured his leave would be approved.
Five days later, his job offer was revoked.
In an email from hospital leadership, the oncologist was informed that he had “declined employment” by failing to sign a revised employment contract sent to him 2 weeks prior when he was out of state on a preapproved vacation, according to the lawsuit.
The lawsuit alleges that Dr. Peddada was wrongfully discharged due to his disability after Centura “exploited [his] extensive patient base, referral network, and reputation to generate growth and profit.”
Colorado employment law attorney Deborah Yim, Esq., who is not involved in Peddada’s case, told this news organization that the ADA requires employers to provide reasonable accommodations for physical or mental impairments that substantially limit at least one major life activity, except when the request imposes an undue hardship on the employer.
“Depression and related mental health conditions would qualify, depending on the circumstances, and courts have certainly found them to be qualifying disabilities entitled to ADA protection in the past,” she said.
Not all employers are receptive to doctors’ needs, says the leadership team at Physicians Just Equity, an organization providing peer support to doctors experiencing workplace conflicts like discrimination and retaliation. They say that Dr. Peddada’s experience, where disclosing burnout results in being “ostracized, penalized, and ultimately ousted,” is the rule rather than the exception.
“Dr. Peddada’s case represents the unfortunate reality faced by many physicians in today’s clinical landscape,” the organization’s board of directors said in a written statement. “The imbalance of unreasonable professional demands, the lack of autonomy, moral injury, and disintegrating practice rewards is unsustainable for the medical professional.”
“Retaliation by employers after speaking up against this imbalance [and] requesting support and time to rejuvenate is a grave failure of health care systems that prioritize the business of delivering health care over the health, well-being, and satisfaction of their most valuable resource – the physician,” the board added in their statement.
Dr. Peddada has since closed his private practice and works as an independent contractor and consultant, his attorney, Iris Halpern, JD, said in an interview. She says Centura could have honored the accommodation request or suggested another option that met his needs, but “not only were they unsupportive, they terminated him.”
Ms. Yim says the parties will have opportunities to reach a settlement and resolve the dispute as the case works through the court system. Otherwise, Dr. Peddada and Centura may eventually head to trial.
Current state of physician burnout
The state of physician burnout is certainly a concerning one. More than half (53%) of physicians responding to this year’s Medscape Physician Burnout & Depression Report said they are burned out. Nearly one-quarter reported feeling depressed. Some of the top reasons they cited were too many bureaucratic tasks (61%), too many work hours (37%), and lack of autonomy (31%).
A 2022 study by the Mayo Clinic found a substantial increase in physician burnout in the first 2 years of the pandemic, with doctors reporting rising emotional exhaustion and depersonalization.
Although burnout affects many physicians and is a priority focus of the National Academy of Medicine’s plan to restore workforce well-being, admitting it is often seen as taboo and can imperil a doctor’s career. In the Medscape report, for example, 39% of physicians said they would not even consider professional treatment for burnout, with many commenting that they would just deal with it themselves.
“Many physicians are frightened to take time out for self-care because [they] fear losing their job, being stigmatized, and potentially ending their careers,” said Dr. Peddada, adding that physicians are commonly asked questions about their mental health when applying for hospital privileges. He says this dynamic forces them to choose between getting help or ignoring their true feelings, leading to poor quality of care and patient safety risks.
Medical licensing boards probe physicians’ mental health, too. As part of its #FightingForDocs campaign, the American Medical Association hopes to remove the stigma around burnout and depression and advocates for licensing boards to revise questions that may discourage physicians from seeking assistance. The AMA recommends that physicians only disclose current physical or mental conditions affecting their ability to practice.
Pringl Miller, MD, founder and executive director of Physician Just Equity, told Medscape that improving physician wellness requires structural change.
“Physicians (who) experience burnout without the proper accommodations run the risk of personal harm, because most physicians will prioritize the health and well-being of their patients over themselves ... [resulting in] suboptimal and unsafe patient care,” she said.
Helping doctors regain a sense of purpose
One change involves reframing how the health care industry thinks about and approaches burnout, says Steven Siegel, MD, chief mental health and wellness officer with Keck Medicine of USC. He told this news organization that these discussions should enhance the physician’s sense of purpose.
“Some people treat burnout as a concrete disorder like cancer, instead of saying, ‘I’m feeling exhausted, demoralized, and don’t enjoy my job anymore. What can we do to restore my enthusiasm for work?’ ”
Dr. Siegel recognizes that these issues existed before the pandemic and have only worsened as physicians feel less connected to and satisfied with their profession – a byproduct, he says, of the commercialization of medicine.
“We’ve moved from practices to systems, then from small to large systems, where it seems the path to survival is cutting costs and increasing margins, even among nonprofits.”
The road ahead
Making headway on these problems will take time. Last year, Keck Medicine received a $2 million grant to launch a 3-year randomized clinical trial to help reconnect physicians and other clinicians with their work. Dr. Siegel says the trial may serve as a national pilot program and will eventually grow to include 400 volunteers.
The trial will investigate the effectiveness of three possible interventions: (1) teaching people how to regulate their internal narratives and emotions through techniques like cognitive behavioral therapy and acceptance and commitment therapy; (2) providing customized EHR training to reduce the burden of navigating the system; and (3) allowing physicians to weigh in on workflow changes.
“We put physicians on teams that make the decisions about workflows,” said Dr. Siegel. The arrangement can give people the agency they desire and help them understand why an idea might not be plausible, which enriches future suggestions and discussions, he says.
A version of this article first appeared on Medscape.com.
By the end of 2021, Anuj Peddada, MD, had hit a wall. He couldn’t sleep, couldn’t concentrate, erupted in anger, and felt isolated personally and professionally. To temper pandemic-driven pressures, the Colorado radiation oncologist took an 8-week stress management and resiliency course, but the feelings kept creeping back.
Still, Dr. Peddada, in his own private practice, pushed through, working 60-hour weeks and carrying the workload of two physicians. It wasn’t until he caught himself making uncharacteristic medical errors, including radiation planning for the wrong site, that he knew he needed help – and possibly a temporary break from medicine.
There was just one hitch: He was closing his private practice to start a new in-house job with Centura Health, the Colorado Springs hospital he’d contracted with for over 20 years.
Given the long-standing relationship – Dr. Peddada’s image graced some of the company’s marketing billboards – he expected Centura would understand when, on his doctor’s recommendation, he requested a short-term medical leave that would delay his start date by 1 month.
Instead, Centura abruptly rescinded the employment offer, leaving Dr. Peddada jobless and with no recourse but to sue.
“I was blindsided. The hospital had a physician resiliency program that claimed to encourage physicians to seek help, [so] I thought they would be completely supportive and understanding,” Dr. Peddada said.
He told this news organization that he was naive to have been so honest with the hospital he’d long served as a contractor, including the decade-plus he›d spent directing its radiation oncology department.
“It is exceedingly painful to see hospital leadership use me in their advertisement[s] ... trying to profit off my reputation and work after devastating my career.”
The lawsuit Dr. Peddada filed in July in Colorado federal district court may offer a rare glimpse of the potential career ramifications of seeking help for physician burnout. Despite employers’ oft-stated support for physician wellness, Dr. Peddada’s experience may serve as a cautionary tale for doctors who are open about their struggles.
Centura Health did not respond to requests for comment. In court documents, the health system’s attorneys asked for more time to respond to Dr. Peddada’s complaint.
A plea for help
In the complaint, Dr. Peddada and his attorneys claim that Centura violated the state’s Anti-Discrimination Act and the Americans with Disabilities Act (ADA) when it failed to offer reasonable accommodations after he began experiencing “physiological and psychological symptoms corresponding to burnout.”
Since 1999, Dr. Peddada had contracted exclusively with Centura to provide oncology services at its hospital, Penrose Cancer Center, and began covering a second Centura location in 2021. As medical director of Penrose’s radiation oncology department, he helped establish a community nurse navigator program and accounted for 75% of Centura’s radiation oncology referrals, according to the complaint.
But when his symptoms and fear for the safety of his patients became unbearable, Dr. Peddada requested an urgent evaluation from his primary care physician, who diagnosed him with “physician burnout” and recommended medical leave.
Shortly after presenting the leave request to Centura, rumors began circulating that he was having a “nervous breakdown,” the complaint noted. Dr. Peddada worried that perhaps his private health information was being shared with hospital employees.
After meeting with the hospital’s head of physician resiliency and agreeing to undergo a peer review evaluation by the Colorado Physician Health Program, which would decide the reinstatement timeline and if further therapy was necessary, Dr. Peddada was assured his leave would be approved.
Five days later, his job offer was revoked.
In an email from hospital leadership, the oncologist was informed that he had “declined employment” by failing to sign a revised employment contract sent to him 2 weeks prior when he was out of state on a preapproved vacation, according to the lawsuit.
The lawsuit alleges that Dr. Peddada was wrongfully discharged due to his disability after Centura “exploited [his] extensive patient base, referral network, and reputation to generate growth and profit.”
Colorado employment law attorney Deborah Yim, Esq., who is not involved in Peddada’s case, told this news organization that the ADA requires employers to provide reasonable accommodations for physical or mental impairments that substantially limit at least one major life activity, except when the request imposes an undue hardship on the employer.
“Depression and related mental health conditions would qualify, depending on the circumstances, and courts have certainly found them to be qualifying disabilities entitled to ADA protection in the past,” she said.
Not all employers are receptive to doctors’ needs, says the leadership team at Physicians Just Equity, an organization providing peer support to doctors experiencing workplace conflicts like discrimination and retaliation. They say that Dr. Peddada’s experience, where disclosing burnout results in being “ostracized, penalized, and ultimately ousted,” is the rule rather than the exception.
“Dr. Peddada’s case represents the unfortunate reality faced by many physicians in today’s clinical landscape,” the organization’s board of directors said in a written statement. “The imbalance of unreasonable professional demands, the lack of autonomy, moral injury, and disintegrating practice rewards is unsustainable for the medical professional.”
“Retaliation by employers after speaking up against this imbalance [and] requesting support and time to rejuvenate is a grave failure of health care systems that prioritize the business of delivering health care over the health, well-being, and satisfaction of their most valuable resource – the physician,” the board added in their statement.
Dr. Peddada has since closed his private practice and works as an independent contractor and consultant, his attorney, Iris Halpern, JD, said in an interview. She says Centura could have honored the accommodation request or suggested another option that met his needs, but “not only were they unsupportive, they terminated him.”
Ms. Yim says the parties will have opportunities to reach a settlement and resolve the dispute as the case works through the court system. Otherwise, Dr. Peddada and Centura may eventually head to trial.
Current state of physician burnout
The state of physician burnout is certainly a concerning one. More than half (53%) of physicians responding to this year’s Medscape Physician Burnout & Depression Report said they are burned out. Nearly one-quarter reported feeling depressed. Some of the top reasons they cited were too many bureaucratic tasks (61%), too many work hours (37%), and lack of autonomy (31%).
A 2022 study by the Mayo Clinic found a substantial increase in physician burnout in the first 2 years of the pandemic, with doctors reporting rising emotional exhaustion and depersonalization.
Although burnout affects many physicians and is a priority focus of the National Academy of Medicine’s plan to restore workforce well-being, admitting it is often seen as taboo and can imperil a doctor’s career. In the Medscape report, for example, 39% of physicians said they would not even consider professional treatment for burnout, with many commenting that they would just deal with it themselves.
“Many physicians are frightened to take time out for self-care because [they] fear losing their job, being stigmatized, and potentially ending their careers,” said Dr. Peddada, adding that physicians are commonly asked questions about their mental health when applying for hospital privileges. He says this dynamic forces them to choose between getting help or ignoring their true feelings, leading to poor quality of care and patient safety risks.
Medical licensing boards probe physicians’ mental health, too. As part of its #FightingForDocs campaign, the American Medical Association hopes to remove the stigma around burnout and depression and advocates for licensing boards to revise questions that may discourage physicians from seeking assistance. The AMA recommends that physicians only disclose current physical or mental conditions affecting their ability to practice.
Pringl Miller, MD, founder and executive director of Physician Just Equity, told Medscape that improving physician wellness requires structural change.
“Physicians (who) experience burnout without the proper accommodations run the risk of personal harm, because most physicians will prioritize the health and well-being of their patients over themselves ... [resulting in] suboptimal and unsafe patient care,” she said.
Helping doctors regain a sense of purpose
One change involves reframing how the health care industry thinks about and approaches burnout, says Steven Siegel, MD, chief mental health and wellness officer with Keck Medicine of USC. He told this news organization that these discussions should enhance the physician’s sense of purpose.
“Some people treat burnout as a concrete disorder like cancer, instead of saying, ‘I’m feeling exhausted, demoralized, and don’t enjoy my job anymore. What can we do to restore my enthusiasm for work?’ ”
Dr. Siegel recognizes that these issues existed before the pandemic and have only worsened as physicians feel less connected to and satisfied with their profession – a byproduct, he says, of the commercialization of medicine.
“We’ve moved from practices to systems, then from small to large systems, where it seems the path to survival is cutting costs and increasing margins, even among nonprofits.”
The road ahead
Making headway on these problems will take time. Last year, Keck Medicine received a $2 million grant to launch a 3-year randomized clinical trial to help reconnect physicians and other clinicians with their work. Dr. Siegel says the trial may serve as a national pilot program and will eventually grow to include 400 volunteers.
The trial will investigate the effectiveness of three possible interventions: (1) teaching people how to regulate their internal narratives and emotions through techniques like cognitive behavioral therapy and acceptance and commitment therapy; (2) providing customized EHR training to reduce the burden of navigating the system; and (3) allowing physicians to weigh in on workflow changes.
“We put physicians on teams that make the decisions about workflows,” said Dr. Siegel. The arrangement can give people the agency they desire and help them understand why an idea might not be plausible, which enriches future suggestions and discussions, he says.
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