Randy Dotinga

Harvard Medical School’s Sharon K. Inouye, MD, MPH, is editor in chief of JAMA Internal Medicine and a leading voice in American gerontology. We asked her to choose five of the influential journal’s most impactful studies from 2023 and highlight important take-home messages for internists and their colleagues.
 

Q: One of the studies you chose suggests that the antiviral nirmatrelvir (Paxlovid) can ward off long COVID. Could you recap the findings?

A: Researchers followed a group of more than 280,000 Department of Veterans Affairs patients who were seen in 2022, had a positive COVID test, and had at least one risk factor for severe COVID. They focused on those who survived to 30 days after their COVID infection and compared those who received the drug within the first 5 days of a positive test with an equivalent control group.

They found that 13 long COVID symptoms were all significantly less common (relative risk = 0.74) in those who received nirmatrelvir. This was true no matter whether they’d ever had a COVID vaccination.
 

Q: How should this research affect clinical practice?

A: You can’t generalize from this to everyone because, of course, not everyone was included in this study. But it is highly suggestive that this drug is very effective for preventing long COVID.

Nirmatrelvir was touted as being able to shorten duration of illness and prevent hospitalization. But if you were low risk or you were already well into your COVID course, it wasn’t like rush, rush, rush to the doctor to get it.

This changes that equation because we know long COVID is such a huge issue. The vast majority of doctors who work with COVID patients and know this are now being more aggressive about prescribing it.
 

Q: What about patients whom the CDC considers to be at less risk — people with up-to-date vaccinations who are under 50 with mild-to-moderate COVID and no higher-risk medical conditions? Should they take nirmatrelvir?

A: The evidence is not 100% in yet. A study like this one needs to be repeated and include younger people without any risk factors to see if we see the same thing. So it’s a personal choice, and a personal calculus needs to be done. A lot of people are making that choice [to take the drug], and it can be a rational decision.

Q: You also chose a study that links high thyroid hormone levels to higher rates of dementia. What did it reveal?

A: This study looks at patients who had thyrotoxicosis — a thyroid level that’s too high — from hormone produced endogenously, and exogenously. Researchers tracked almost 66,000 patients aged 65 and older and found that thyrotoxicosis from all causes, whether it was endogenous or exogenous, was linked to an increased risk of dementia in a dose-response relationship (adjusted hazard ratio = 1.39).

Q: Is there a clinical take-home message here?

A: When we start patients on thyroid medication, they don’t always get reassessed on a regular basis. Given this finding, a TSH [thyroid-stimulating hormone] level is indicated during the annual wellness check that patients on Medicare can get every year.

Q: Is TSH measured as part of routine blood tests?

A: No it’s not. It has to be ordered. I think that’s why we’re seeing this problem to begin with — because it’s not something we all have awareness about. I wasn’t aware myself that mildly high levels of thyroid could increase the risk of cognitive impairment. Certainly, I’m going to be much more aware in my practice.

Q: You also picked a study about silicosis in workers who are exposed to dust when they make engineered stone countertops, also known as quartz countertops. What were the findings?

A: Silicosis is a very serious lung condition that develops from exposure to crystalline silica. Essentially, sand gets inhaled into the lungs. Workers can be exposed when they’re making engineered stone countertops, the most popular countertops now in the United States.

This study is based on statewide surveys from 2019 to 2022 that the California Department of Public Health does routinely. They gathered cases of silicosis and found 52 — all men with an average age of 45. All but one were Latino immigrants, and most either had no insurance or very poor insurance.
 

Q: The study found that “diagnosis was delayed in 58%, with 38% presenting with advanced disease (progressive massive fibrosis), and 19% died.” What does that tell you?

A: It’s a very serious condition. Once it gets to the advanced stage, it will just continue to progress, and the person will die. That’s why it’s so important to know that it’s absolutely preventable.

Q: Is there a message here for internists?

A: If you treat a lot of immigrants or work in an area where there are a lot of industrial workers, you’re going to want to have a very high suspicion about it. If you see an atypical pattern on the chest x-ray or via diffusion scoring, have a low threshold for getting a pulmonary function test.

Doctors need to be aware and diagnose this very quickly. When patients present, you can pull them out of that work environment or put mitigation systems into place.
 

Q: California regulators were expected to put emergency rules into place in late December to protect workers. Did this study play a role in focusing attention on the problem?

A: This article, along with a commentary and podcast that we put out, really helped with advocacy to improve health and safety for workers at stone-cutting and fabrication shops.

Q: You were impressed by another study about airborne dangers, this one linking air pollution to dementia. What did researchers discover?

A: [This analysis] of more than 27,000 people in the Health and Retirement Study, a respected and rich database, found that exposure to air pollution was associated with greater rates of dementia — an increase of about 8% a year. Exposure to agricultural emissions and wildfire smoke were most robustly associated with a greater risk of dementia.

Q: How are these findings important, especially in light of the unhealthy air spawned by recent wildfires in the United States and Canada?

A: Studies like this will make it even more compelling that we are better prepared for air quality issues.

I grew up in Los Angeles, where smog and pollution were very big issues. I was constantly hearing about various mitigation strategies that were going into place. But after I moved to the East Coast, I almost never heard about prevention.

Now, I’m hoping we can keep this topic in the national conversation.
 

Q: You also highlighted a systematic review of the use of restraints in the emergency department. Why did you choose this research?

A: At JAMA Internal Medicine, we’re really focused on ways we can address health disparities and raise awareness of potential unconscious bias.

This review looked at 10 studies that included more than 2.5 million patient encounters, including 24,000 incidents of physical restraint use. They found that the overall rate of use of restraints was low at below 1%.

But when they are used, Black patients were 1.3 times more likely to be restrained than White patients.
 

Q: What’s the message here?

A: This is an important start to recognizing these differences and then changing our behavior. Perhaps restraints don’t need to be used as often in light of evidence, for example, of increased rates of misdiagnosis of psychosis in the Black population.

Q: How should physicians change their approach to restraints?

A: Restraints are not to be used to control disruption — wild behavior or verbal outbursts. They’re for when someone is a danger to themselves or others.

Dr. Inouye has no conflicts of interest.

Harvard Medical School’s Sharon K. Inouye, MD, MPH, is editor in chief of JAMA Internal Medicine and a leading voice in American gerontology. We asked her to choose five of the influential journal’s most impactful studies from 2023 and highlight important take-home messages for internists and their colleagues.
 

Q: One of the studies you chose suggests that the antiviral nirmatrelvir (Paxlovid) can ward off long COVID. Could you recap the findings?

A: Researchers followed a group of more than 280,000 Department of Veterans Affairs patients who were seen in 2022, had a positive COVID test, and had at least one risk factor for severe COVID. They focused on those who survived to 30 days after their COVID infection and compared those who received the drug within the first 5 days of a positive test with an equivalent control group.

They found that 13 long COVID symptoms were all significantly less common (relative risk = 0.74) in those who received nirmatrelvir. This was true no matter whether they’d ever had a COVID vaccination.
 

Q: How should this research affect clinical practice?

A: You can’t generalize from this to everyone because, of course, not everyone was included in this study. But it is highly suggestive that this drug is very effective for preventing long COVID.

Nirmatrelvir was touted as being able to shorten duration of illness and prevent hospitalization. But if you were low risk or you were already well into your COVID course, it wasn’t like rush, rush, rush to the doctor to get it.

This changes that equation because we know long COVID is such a huge issue. The vast majority of doctors who work with COVID patients and know this are now being more aggressive about prescribing it.
 

Q: What about patients whom the CDC considers to be at less risk — people with up-to-date vaccinations who are under 50 with mild-to-moderate COVID and no higher-risk medical conditions? Should they take nirmatrelvir?

A: The evidence is not 100% in yet. A study like this one needs to be repeated and include younger people without any risk factors to see if we see the same thing. So it’s a personal choice, and a personal calculus needs to be done. A lot of people are making that choice [to take the drug], and it can be a rational decision.

Q: You also chose a study that links high thyroid hormone levels to higher rates of dementia. What did it reveal?

A: This study looks at patients who had thyrotoxicosis — a thyroid level that’s too high — from hormone produced endogenously, and exogenously. Researchers tracked almost 66,000 patients aged 65 and older and found that thyrotoxicosis from all causes, whether it was endogenous or exogenous, was linked to an increased risk of dementia in a dose-response relationship (adjusted hazard ratio = 1.39).

Q: Is there a clinical take-home message here?

A: When we start patients on thyroid medication, they don’t always get reassessed on a regular basis. Given this finding, a TSH [thyroid-stimulating hormone] level is indicated during the annual wellness check that patients on Medicare can get every year.

Q: Is TSH measured as part of routine blood tests?

A: No it’s not. It has to be ordered. I think that’s why we’re seeing this problem to begin with — because it’s not something we all have awareness about. I wasn’t aware myself that mildly high levels of thyroid could increase the risk of cognitive impairment. Certainly, I’m going to be much more aware in my practice.

Q: You also picked a study about silicosis in workers who are exposed to dust when they make engineered stone countertops, also known as quartz countertops. What were the findings?

A: Silicosis is a very serious lung condition that develops from exposure to crystalline silica. Essentially, sand gets inhaled into the lungs. Workers can be exposed when they’re making engineered stone countertops, the most popular countertops now in the United States.

This study is based on statewide surveys from 2019 to 2022 that the California Department of Public Health does routinely. They gathered cases of silicosis and found 52 — all men with an average age of 45. All but one were Latino immigrants, and most either had no insurance or very poor insurance.
 

Q: The study found that “diagnosis was delayed in 58%, with 38% presenting with advanced disease (progressive massive fibrosis), and 19% died.” What does that tell you?

A: It’s a very serious condition. Once it gets to the advanced stage, it will just continue to progress, and the person will die. That’s why it’s so important to know that it’s absolutely preventable.

Q: Is there a message here for internists?

A: If you treat a lot of immigrants or work in an area where there are a lot of industrial workers, you’re going to want to have a very high suspicion about it. If you see an atypical pattern on the chest x-ray or via diffusion scoring, have a low threshold for getting a pulmonary function test.

Doctors need to be aware and diagnose this very quickly. When patients present, you can pull them out of that work environment or put mitigation systems into place.
 

Q: California regulators were expected to put emergency rules into place in late December to protect workers. Did this study play a role in focusing attention on the problem?

A: This article, along with a commentary and podcast that we put out, really helped with advocacy to improve health and safety for workers at stone-cutting and fabrication shops.

Q: You were impressed by another study about airborne dangers, this one linking air pollution to dementia. What did researchers discover?

A: [This analysis] of more than 27,000 people in the Health and Retirement Study, a respected and rich database, found that exposure to air pollution was associated with greater rates of dementia — an increase of about 8% a year. Exposure to agricultural emissions and wildfire smoke were most robustly associated with a greater risk of dementia.

Q: How are these findings important, especially in light of the unhealthy air spawned by recent wildfires in the United States and Canada?

A: Studies like this will make it even more compelling that we are better prepared for air quality issues.

I grew up in Los Angeles, where smog and pollution were very big issues. I was constantly hearing about various mitigation strategies that were going into place. But after I moved to the East Coast, I almost never heard about prevention.

Now, I’m hoping we can keep this topic in the national conversation.
 

Q: You also highlighted a systematic review of the use of restraints in the emergency department. Why did you choose this research?

A: At JAMA Internal Medicine, we’re really focused on ways we can address health disparities and raise awareness of potential unconscious bias.

This review looked at 10 studies that included more than 2.5 million patient encounters, including 24,000 incidents of physical restraint use. They found that the overall rate of use of restraints was low at below 1%.

But when they are used, Black patients were 1.3 times more likely to be restrained than White patients.
 

Q: What’s the message here?

A: This is an important start to recognizing these differences and then changing our behavior. Perhaps restraints don’t need to be used as often in light of evidence, for example, of increased rates of misdiagnosis of psychosis in the Black population.

Q: How should physicians change their approach to restraints?

A: Restraints are not to be used to control disruption — wild behavior or verbal outbursts. They’re for when someone is a danger to themselves or others.

Dr. Inouye has no conflicts of interest.

Harvard Medical School’s Sharon K. Inouye, MD, MPH, is editor in chief of JAMA Internal Medicine and a leading voice in American gerontology. We asked her to choose five of the influential journal’s most impactful studies from 2023 and highlight important take-home messages for internists and their colleagues.
 

Q: One of the studies you chose suggests that the antiviral nirmatrelvir (Paxlovid) can ward off long COVID. Could you recap the findings?

A: Researchers followed a group of more than 280,000 Department of Veterans Affairs patients who were seen in 2022, had a positive COVID test, and had at least one risk factor for severe COVID. They focused on those who survived to 30 days after their COVID infection and compared those who received the drug within the first 5 days of a positive test with an equivalent control group.

They found that 13 long COVID symptoms were all significantly less common (relative risk = 0.74) in those who received nirmatrelvir. This was true no matter whether they’d ever had a COVID vaccination.
 

Q: How should this research affect clinical practice?

A: You can’t generalize from this to everyone because, of course, not everyone was included in this study. But it is highly suggestive that this drug is very effective for preventing long COVID.

Nirmatrelvir was touted as being able to shorten duration of illness and prevent hospitalization. But if you were low risk or you were already well into your COVID course, it wasn’t like rush, rush, rush to the doctor to get it.

This changes that equation because we know long COVID is such a huge issue. The vast majority of doctors who work with COVID patients and know this are now being more aggressive about prescribing it.
 

Q: What about patients whom the CDC considers to be at less risk — people with up-to-date vaccinations who are under 50 with mild-to-moderate COVID and no higher-risk medical conditions? Should they take nirmatrelvir?

A: The evidence is not 100% in yet. A study like this one needs to be repeated and include younger people without any risk factors to see if we see the same thing. So it’s a personal choice, and a personal calculus needs to be done. A lot of people are making that choice [to take the drug], and it can be a rational decision.

Q: You also chose a study that links high thyroid hormone levels to higher rates of dementia. What did it reveal?

A: This study looks at patients who had thyrotoxicosis — a thyroid level that’s too high — from hormone produced endogenously, and exogenously. Researchers tracked almost 66,000 patients aged 65 and older and found that thyrotoxicosis from all causes, whether it was endogenous or exogenous, was linked to an increased risk of dementia in a dose-response relationship (adjusted hazard ratio = 1.39).

Q: Is there a clinical take-home message here?

A: When we start patients on thyroid medication, they don’t always get reassessed on a regular basis. Given this finding, a TSH [thyroid-stimulating hormone] level is indicated during the annual wellness check that patients on Medicare can get every year.

Q: Is TSH measured as part of routine blood tests?

A: No it’s not. It has to be ordered. I think that’s why we’re seeing this problem to begin with — because it’s not something we all have awareness about. I wasn’t aware myself that mildly high levels of thyroid could increase the risk of cognitive impairment. Certainly, I’m going to be much more aware in my practice.

Q: You also picked a study about silicosis in workers who are exposed to dust when they make engineered stone countertops, also known as quartz countertops. What were the findings?

A: Silicosis is a very serious lung condition that develops from exposure to crystalline silica. Essentially, sand gets inhaled into the lungs. Workers can be exposed when they’re making engineered stone countertops, the most popular countertops now in the United States.

This study is based on statewide surveys from 2019 to 2022 that the California Department of Public Health does routinely. They gathered cases of silicosis and found 52 — all men with an average age of 45. All but one were Latino immigrants, and most either had no insurance or very poor insurance.
 

Q: The study found that “diagnosis was delayed in 58%, with 38% presenting with advanced disease (progressive massive fibrosis), and 19% died.” What does that tell you?

A: It’s a very serious condition. Once it gets to the advanced stage, it will just continue to progress, and the person will die. That’s why it’s so important to know that it’s absolutely preventable.

Q: Is there a message here for internists?

A: If you treat a lot of immigrants or work in an area where there are a lot of industrial workers, you’re going to want to have a very high suspicion about it. If you see an atypical pattern on the chest x-ray or via diffusion scoring, have a low threshold for getting a pulmonary function test.

Doctors need to be aware and diagnose this very quickly. When patients present, you can pull them out of that work environment or put mitigation systems into place.
 

Q: California regulators were expected to put emergency rules into place in late December to protect workers. Did this study play a role in focusing attention on the problem?

A: This article, along with a commentary and podcast that we put out, really helped with advocacy to improve health and safety for workers at stone-cutting and fabrication shops.

Q: You were impressed by another study about airborne dangers, this one linking air pollution to dementia. What did researchers discover?

A: [This analysis] of more than 27,000 people in the Health and Retirement Study, a respected and rich database, found that exposure to air pollution was associated with greater rates of dementia — an increase of about 8% a year. Exposure to agricultural emissions and wildfire smoke were most robustly associated with a greater risk of dementia.

Q: How are these findings important, especially in light of the unhealthy air spawned by recent wildfires in the United States and Canada?

A: Studies like this will make it even more compelling that we are better prepared for air quality issues.

I grew up in Los Angeles, where smog and pollution were very big issues. I was constantly hearing about various mitigation strategies that were going into place. But after I moved to the East Coast, I almost never heard about prevention.

Now, I’m hoping we can keep this topic in the national conversation.
 

Q: You also highlighted a systematic review of the use of restraints in the emergency department. Why did you choose this research?

A: At JAMA Internal Medicine, we’re really focused on ways we can address health disparities and raise awareness of potential unconscious bias.

This review looked at 10 studies that included more than 2.5 million patient encounters, including 24,000 incidents of physical restraint use. They found that the overall rate of use of restraints was low at below 1%.

But when they are used, Black patients were 1.3 times more likely to be restrained than White patients.
 

Q: What’s the message here?

A: This is an important start to recognizing these differences and then changing our behavior. Perhaps restraints don’t need to be used as often in light of evidence, for example, of increased rates of misdiagnosis of psychosis in the Black population.

Q: How should physicians change their approach to restraints?

A: Restraints are not to be used to control disruption — wild behavior or verbal outbursts. They’re for when someone is a danger to themselves or others.

Dr. Inouye has no conflicts of interest.

The past year brought major changes in preventive standards for anxiety, HIV, and RSV along with new guidelines for the treatment of atrial fibrillation. For insight into the effect on internal medicine, we turned to Sarah Candler, MD, MPH, a Houston internist who specializes in the care of high-risk older adults.


Q: Which new prevention guidelines had the most impact on you over the past year?

A: I’m a primary care doctor, and most of the internal medicine updates that are interesting to me focus on how we can keep people from getting sick in the first place. That’s especially important in light of the fact that we had a decrease in life expectancy of 2 years [it finally rose slightly in 2022] and widening of the gender gap in life expectancy for men and women.

I’m excited to see new recommendations from the U.S. Preventive Services Task Force, including a new one about using PREP [pre-exposure prophylaxis] to preventively treat anyone who’s at risk for getting HIV. That’s a big one because it’s one of the first times that we’ve identified at-risk groups for screening based on social risk factors, not gender, age, or genetics.

The new recommendation is PREP for anyone who’s at risk for getting HIV because they have a partner with HIV, had an sexually transmitted infection in the last 6 months, or a history of inconsistent or no condom use with partners with unknown HIV status.

PREP therapy is something that most primary care physicians can either do or learn how to do pretty easily. But the treatment does require maintenance and monitoring.
 

Q: How firm is this recommendation?

A: The task force gives different grades for their recommendations based on how strong the evidence is. For the guidelines about PREP, they give a grade of A. That means this is top of the class: You should definitely do this.


Q: What are the best strategies to ask patients personal questions about their sex lives in order to evaluate their risk?

A: A lot of internal medicine physicians are getting pretty good at this. We see it as part of our job just the same way as we asked things like, “How often are you walking?” and “Have you been feeling down?”

There’s no one right way to have a conversation like that. But it’s key to say, as I do to my patients, that “I’m not here to judge anything. I am truly here to gather information and make recommendations to you as a partner in your care.”  
 

Q: What other guidelines made an impact in 2023?

A: The U.S. Preventive Services Task Force made a recommendation to screen adults aged 18-64 for anxiety, and this guidance got a B grade. [The task force said there’s not enough evidence to support routine anxiety screening in adults 65 and older.]

The new recommendations is a sign that we’re doing a better job at making treatment of those diseases more acceptable. This is also another example of the medical community recognizing that internal medicine physicians are pretty good at identifying and treating mental health.
 

Q: How do you figure out whether to treat depression/anxiety yourself or refer patients to specialists?

A: As a primary care physician, I feel comfortable diagnosing and managing some mental health disease in my own practice. There are FDA-approved medications for both anxiety and depression that are easily managed by a primary care physician.

And there’s something to the therapeutic relationship, to naming and identifying these conditions with your patients. Some patients feel a bit of relief just knowing that they have a diagnosis.
 

Q: What should internists know about the new CDC guidelines that promote discussing RSV vaccines with patients who are over 60?

A: The vaccines are recommended for folks who have underlying conditions like lung disease or heart disease. Those are the ones who end up getting really, really sick. There are two adult vaccines that are available, and there’s not a preference for one over the other.

The vaccines are both protein-based, like the old-school versions of vaccines, not the mRNA vaccines that we’ve all been hearing more about through COVID. Anybody who’s reluctant to take an mRNA vaccine can rest assured that the RSV is not protein-based. And they are single-dose vaccines, which is helpful.  
 

Q: What else should internists know about that was new in 2023?

A: I’m super excited about how cardiologists are thinking about atrial fibrillation. In 2023, the American College of Cardiology and the American Heart Association came up with a giant overhaul of how they look at atrial fibrillation. They classify it in stages and allows us to think about stopping it before it starts.

They’re talking about something they’re calling preclinical or subclinical atrial fibrillation, which you may detect on wearables like somebody’s watch or another tool used to monitor heart rate or exercise. It might be the first harbinger that there’s something wrong with the heart rate, and they may not even have symptoms of it. [A 2023 study in The New England Journal of Medicine linked the anticoagulant apixaban, or Eliquis, to a 37% lower risk of stroke and systemic embolism rates in older patients with subclinical atrial fibrillation but an 80% higher risk of major bleeding vs. aspirin therapy.]

And they’re now recommending early rhythm control.
 

Q: What does early rhythm control mean for patients and physicians?

A: For the longest time, we have thought about atrial fibrillation treatment in terms of rate control and not worrying too much about the rhythm. But now we recognize that it’s actually really important that we get the rhythm under control because physical changes to the heart can lead to permanent damage.

So now they’re recommending catheter ablation as first-line therapy in some patients as a class 1 recommendation because heart function is already decreased. Improving the ability of the heart to beat with a regular rhythm can lead to improvement of function. This was unheard of even 5 years ago.
 

Q: Should internists be more willing to refer patients with atrial fibrillation to cardiologists?

A: Yes, I think so. One of the biggest changes for me is that I am going to refer new diagnoses of atrial fibrillation to a cardiologist. And I’m going to ask patients if they have wearable devices because sometimes those things might tell me about something like subclinical atrial fibrillation.

Q: There’s also detailed data about atrial fibrillation risk factors, which include older age, smoking, sedentary lifestyle, alcohol use, diabetes, height, obesity, diabetes, and others. Is this information useful?

A: It’s a really great tool to have in the arsenal because it helps me have shared decision-making conversations with my patients in a way that’s much more convincing. A patient might say, “Why do you care if I drink so much? My liver levels are fine.” And I can say, “It’s going to be a risk factor for having problems with your heart.”

For better or worse, people really take the heart very seriously, I am an internal medicine physician, so I love all the organs equally. But man, people get pretty scared when you tell them something can affect their heart. So when I talk to patients about their risk factors, it’s going to really be helpful that I can remind them of the impact that some of these lifestyle behaviors can have on their heart health.
 

Dr. Candler has no disclosures.

The past year brought major changes in preventive standards for anxiety, HIV, and RSV along with new guidelines for the treatment of atrial fibrillation. For insight into the effect on internal medicine, we turned to Sarah Candler, MD, MPH, a Houston internist who specializes in the care of high-risk older adults.


Q: Which new prevention guidelines had the most impact on you over the past year?

A: I’m a primary care doctor, and most of the internal medicine updates that are interesting to me focus on how we can keep people from getting sick in the first place. That’s especially important in light of the fact that we had a decrease in life expectancy of 2 years [it finally rose slightly in 2022] and widening of the gender gap in life expectancy for men and women.

I’m excited to see new recommendations from the U.S. Preventive Services Task Force, including a new one about using PREP [pre-exposure prophylaxis] to preventively treat anyone who’s at risk for getting HIV. That’s a big one because it’s one of the first times that we’ve identified at-risk groups for screening based on social risk factors, not gender, age, or genetics.

The new recommendation is PREP for anyone who’s at risk for getting HIV because they have a partner with HIV, had an sexually transmitted infection in the last 6 months, or a history of inconsistent or no condom use with partners with unknown HIV status.

PREP therapy is something that most primary care physicians can either do or learn how to do pretty easily. But the treatment does require maintenance and monitoring.
 

Q: How firm is this recommendation?

A: The task force gives different grades for their recommendations based on how strong the evidence is. For the guidelines about PREP, they give a grade of A. That means this is top of the class: You should definitely do this.


Q: What are the best strategies to ask patients personal questions about their sex lives in order to evaluate their risk?

A: A lot of internal medicine physicians are getting pretty good at this. We see it as part of our job just the same way as we asked things like, “How often are you walking?” and “Have you been feeling down?”

There’s no one right way to have a conversation like that. But it’s key to say, as I do to my patients, that “I’m not here to judge anything. I am truly here to gather information and make recommendations to you as a partner in your care.”  
 

Q: What other guidelines made an impact in 2023?

A: The U.S. Preventive Services Task Force made a recommendation to screen adults aged 18-64 for anxiety, and this guidance got a B grade. [The task force said there’s not enough evidence to support routine anxiety screening in adults 65 and older.]

The new recommendations is a sign that we’re doing a better job at making treatment of those diseases more acceptable. This is also another example of the medical community recognizing that internal medicine physicians are pretty good at identifying and treating mental health.
 

Q: How do you figure out whether to treat depression/anxiety yourself or refer patients to specialists?

A: As a primary care physician, I feel comfortable diagnosing and managing some mental health disease in my own practice. There are FDA-approved medications for both anxiety and depression that are easily managed by a primary care physician.

And there’s something to the therapeutic relationship, to naming and identifying these conditions with your patients. Some patients feel a bit of relief just knowing that they have a diagnosis.
 

Q: What should internists know about the new CDC guidelines that promote discussing RSV vaccines with patients who are over 60?

A: The vaccines are recommended for folks who have underlying conditions like lung disease or heart disease. Those are the ones who end up getting really, really sick. There are two adult vaccines that are available, and there’s not a preference for one over the other.

The vaccines are both protein-based, like the old-school versions of vaccines, not the mRNA vaccines that we’ve all been hearing more about through COVID. Anybody who’s reluctant to take an mRNA vaccine can rest assured that the RSV is not protein-based. And they are single-dose vaccines, which is helpful.  
 

Q: What else should internists know about that was new in 2023?

A: I’m super excited about how cardiologists are thinking about atrial fibrillation. In 2023, the American College of Cardiology and the American Heart Association came up with a giant overhaul of how they look at atrial fibrillation. They classify it in stages and allows us to think about stopping it before it starts.

They’re talking about something they’re calling preclinical or subclinical atrial fibrillation, which you may detect on wearables like somebody’s watch or another tool used to monitor heart rate or exercise. It might be the first harbinger that there’s something wrong with the heart rate, and they may not even have symptoms of it. [A 2023 study in The New England Journal of Medicine linked the anticoagulant apixaban, or Eliquis, to a 37% lower risk of stroke and systemic embolism rates in older patients with subclinical atrial fibrillation but an 80% higher risk of major bleeding vs. aspirin therapy.]

And they’re now recommending early rhythm control.
 

Q: What does early rhythm control mean for patients and physicians?

A: For the longest time, we have thought about atrial fibrillation treatment in terms of rate control and not worrying too much about the rhythm. But now we recognize that it’s actually really important that we get the rhythm under control because physical changes to the heart can lead to permanent damage.

So now they’re recommending catheter ablation as first-line therapy in some patients as a class 1 recommendation because heart function is already decreased. Improving the ability of the heart to beat with a regular rhythm can lead to improvement of function. This was unheard of even 5 years ago.
 

Q: Should internists be more willing to refer patients with atrial fibrillation to cardiologists?

A: Yes, I think so. One of the biggest changes for me is that I am going to refer new diagnoses of atrial fibrillation to a cardiologist. And I’m going to ask patients if they have wearable devices because sometimes those things might tell me about something like subclinical atrial fibrillation.

Q: There’s also detailed data about atrial fibrillation risk factors, which include older age, smoking, sedentary lifestyle, alcohol use, diabetes, height, obesity, diabetes, and others. Is this information useful?

A: It’s a really great tool to have in the arsenal because it helps me have shared decision-making conversations with my patients in a way that’s much more convincing. A patient might say, “Why do you care if I drink so much? My liver levels are fine.” And I can say, “It’s going to be a risk factor for having problems with your heart.”

For better or worse, people really take the heart very seriously, I am an internal medicine physician, so I love all the organs equally. But man, people get pretty scared when you tell them something can affect their heart. So when I talk to patients about their risk factors, it’s going to really be helpful that I can remind them of the impact that some of these lifestyle behaviors can have on their heart health.
 

Dr. Candler has no disclosures.

The past year brought major changes in preventive standards for anxiety, HIV, and RSV along with new guidelines for the treatment of atrial fibrillation. For insight into the effect on internal medicine, we turned to Sarah Candler, MD, MPH, a Houston internist who specializes in the care of high-risk older adults.


Q: Which new prevention guidelines had the most impact on you over the past year?

A: I’m a primary care doctor, and most of the internal medicine updates that are interesting to me focus on how we can keep people from getting sick in the first place. That’s especially important in light of the fact that we had a decrease in life expectancy of 2 years [it finally rose slightly in 2022] and widening of the gender gap in life expectancy for men and women.

I’m excited to see new recommendations from the U.S. Preventive Services Task Force, including a new one about using PREP [pre-exposure prophylaxis] to preventively treat anyone who’s at risk for getting HIV. That’s a big one because it’s one of the first times that we’ve identified at-risk groups for screening based on social risk factors, not gender, age, or genetics.

The new recommendation is PREP for anyone who’s at risk for getting HIV because they have a partner with HIV, had an sexually transmitted infection in the last 6 months, or a history of inconsistent or no condom use with partners with unknown HIV status.

PREP therapy is something that most primary care physicians can either do or learn how to do pretty easily. But the treatment does require maintenance and monitoring.
 

Q: How firm is this recommendation?

A: The task force gives different grades for their recommendations based on how strong the evidence is. For the guidelines about PREP, they give a grade of A. That means this is top of the class: You should definitely do this.


Q: What are the best strategies to ask patients personal questions about their sex lives in order to evaluate their risk?

A: A lot of internal medicine physicians are getting pretty good at this. We see it as part of our job just the same way as we asked things like, “How often are you walking?” and “Have you been feeling down?”

There’s no one right way to have a conversation like that. But it’s key to say, as I do to my patients, that “I’m not here to judge anything. I am truly here to gather information and make recommendations to you as a partner in your care.”  
 

Q: What other guidelines made an impact in 2023?

A: The U.S. Preventive Services Task Force made a recommendation to screen adults aged 18-64 for anxiety, and this guidance got a B grade. [The task force said there’s not enough evidence to support routine anxiety screening in adults 65 and older.]

The new recommendations is a sign that we’re doing a better job at making treatment of those diseases more acceptable. This is also another example of the medical community recognizing that internal medicine physicians are pretty good at identifying and treating mental health.
 

Q: How do you figure out whether to treat depression/anxiety yourself or refer patients to specialists?

A: As a primary care physician, I feel comfortable diagnosing and managing some mental health disease in my own practice. There are FDA-approved medications for both anxiety and depression that are easily managed by a primary care physician.

And there’s something to the therapeutic relationship, to naming and identifying these conditions with your patients. Some patients feel a bit of relief just knowing that they have a diagnosis.
 

Q: What should internists know about the new CDC guidelines that promote discussing RSV vaccines with patients who are over 60?

A: The vaccines are recommended for folks who have underlying conditions like lung disease or heart disease. Those are the ones who end up getting really, really sick. There are two adult vaccines that are available, and there’s not a preference for one over the other.

The vaccines are both protein-based, like the old-school versions of vaccines, not the mRNA vaccines that we’ve all been hearing more about through COVID. Anybody who’s reluctant to take an mRNA vaccine can rest assured that the RSV is not protein-based. And they are single-dose vaccines, which is helpful.  
 

Q: What else should internists know about that was new in 2023?

A: I’m super excited about how cardiologists are thinking about atrial fibrillation. In 2023, the American College of Cardiology and the American Heart Association came up with a giant overhaul of how they look at atrial fibrillation. They classify it in stages and allows us to think about stopping it before it starts.

They’re talking about something they’re calling preclinical or subclinical atrial fibrillation, which you may detect on wearables like somebody’s watch or another tool used to monitor heart rate or exercise. It might be the first harbinger that there’s something wrong with the heart rate, and they may not even have symptoms of it. [A 2023 study in The New England Journal of Medicine linked the anticoagulant apixaban, or Eliquis, to a 37% lower risk of stroke and systemic embolism rates in older patients with subclinical atrial fibrillation but an 80% higher risk of major bleeding vs. aspirin therapy.]

And they’re now recommending early rhythm control.
 

Q: What does early rhythm control mean for patients and physicians?

A: For the longest time, we have thought about atrial fibrillation treatment in terms of rate control and not worrying too much about the rhythm. But now we recognize that it’s actually really important that we get the rhythm under control because physical changes to the heart can lead to permanent damage.

So now they’re recommending catheter ablation as first-line therapy in some patients as a class 1 recommendation because heart function is already decreased. Improving the ability of the heart to beat with a regular rhythm can lead to improvement of function. This was unheard of even 5 years ago.
 

Q: Should internists be more willing to refer patients with atrial fibrillation to cardiologists?

A: Yes, I think so. One of the biggest changes for me is that I am going to refer new diagnoses of atrial fibrillation to a cardiologist. And I’m going to ask patients if they have wearable devices because sometimes those things might tell me about something like subclinical atrial fibrillation.

Q: There’s also detailed data about atrial fibrillation risk factors, which include older age, smoking, sedentary lifestyle, alcohol use, diabetes, height, obesity, diabetes, and others. Is this information useful?

A: It’s a really great tool to have in the arsenal because it helps me have shared decision-making conversations with my patients in a way that’s much more convincing. A patient might say, “Why do you care if I drink so much? My liver levels are fine.” And I can say, “It’s going to be a risk factor for having problems with your heart.”

For better or worse, people really take the heart very seriously, I am an internal medicine physician, so I love all the organs equally. But man, people get pretty scared when you tell them something can affect their heart. So when I talk to patients about their risk factors, it’s going to really be helpful that I can remind them of the impact that some of these lifestyle behaviors can have on their heart health.
 

Dr. Candler has no disclosures.

In a victory for clinicians who fought to keep working regardless of age, a San Diego–based medical group has agreed to settle a federal investigation by paying nearly $7 million to physicians subject to their employer’s policy requiring them to quit at age 75.

In a statement, the US Equal Employment Opportunity Commission (EEOC) said the settlement will resolve an age and disability discrimination charge filed against Scripps Clinic Medical Group. The medical group is part of Scripps Health, a major provider of medical services in the San Diego region that operates five local hospitals.

The EECO said it found “reasonable cause” that the medical group violated the Age Discrimination in Employment Act and the Americans with Disabilities Act.

US health systems are facing lawsuits that claim they’ve engaged in age discrimination by requiring physicians to take cognitive tests when they reach specific ages.

The Scripps medical group’s mandatory retirement policy began in 2016 and was consistent with California law, which specifically allows for mandatory retirement of physicians in medical groups at age 70, Scripps said in a statement, adding that it rescinded the policy in 2018.

“This policy was put in place to enhance patient safety,” Scripps said. “The EEOC took the position while such a policy is expressly legal under California law; it is not allowed under federal law.”

The Federal Age Discrimination in Employment Act, passed in 1967, states that employers may not “fail or refuse to hire or to discharge any individual or otherwise discriminate against any individual with respect to his compensation, terms, conditions, or privileges of employment because of such individual’s age.” There are exceptions, however, in cases of public safety for professions such as air traffic controllers.

California law has a similar provision banning age discrimination, but it makes an exception for “any employee who has attained 70 years of age and is a physician employed by a professional medical corporation, the articles or bylaws of which provide for compulsory retirement.”

In 2020, an estimated 12% of US licensed physicians were at least 70 years old — more than 120,000 in total — up from 9% in a 2010, according to a Federation of State Medical Boards 2021 report.

Scripps Clinic Medical Group settled with the EEOC “without any admission of fault or wrongdoing to avoid the continued expense and distraction of litigation,” its statement said. It agreed to pay $6.875 million to the affected physicians.

When asked about how many physicians were affected by the policy, a Scripps human resources official said, “this was disputed but very few. The policy was only in effect for 2 years, 2016 and 2017. Additionally, by age 75, most doctors have retired. And those who have not almost always have voluntarily limited their practice.”

The Scripps official didn’t respond to questions about the number of patients served by the medical group and how many physicians it employs.

According to the EEOC, the medical group has agreed to tell employees that the policy has been scrapped and must “clarify that the company does not have any policy in which age is a factor in making employment decisions, including termination, retirement, and terms and conditions of employment.”

Scripps Clinic Medical Group also agreed to require division and department heads, executive leadership, and human resources employees to be trained regarding the Age Discrimination in Employment Act and the Americans with Disabilities Act.

A version of this article appeared on Medscape.com.

In a victory for clinicians who fought to keep working regardless of age, a San Diego–based medical group has agreed to settle a federal investigation by paying nearly $7 million to physicians subject to their employer’s policy requiring them to quit at age 75.

In a statement, the US Equal Employment Opportunity Commission (EEOC) said the settlement will resolve an age and disability discrimination charge filed against Scripps Clinic Medical Group. The medical group is part of Scripps Health, a major provider of medical services in the San Diego region that operates five local hospitals.

The EECO said it found “reasonable cause” that the medical group violated the Age Discrimination in Employment Act and the Americans with Disabilities Act.

US health systems are facing lawsuits that claim they’ve engaged in age discrimination by requiring physicians to take cognitive tests when they reach specific ages.

The Scripps medical group’s mandatory retirement policy began in 2016 and was consistent with California law, which specifically allows for mandatory retirement of physicians in medical groups at age 70, Scripps said in a statement, adding that it rescinded the policy in 2018.

“This policy was put in place to enhance patient safety,” Scripps said. “The EEOC took the position while such a policy is expressly legal under California law; it is not allowed under federal law.”

The Federal Age Discrimination in Employment Act, passed in 1967, states that employers may not “fail or refuse to hire or to discharge any individual or otherwise discriminate against any individual with respect to his compensation, terms, conditions, or privileges of employment because of such individual’s age.” There are exceptions, however, in cases of public safety for professions such as air traffic controllers.

California law has a similar provision banning age discrimination, but it makes an exception for “any employee who has attained 70 years of age and is a physician employed by a professional medical corporation, the articles or bylaws of which provide for compulsory retirement.”

In 2020, an estimated 12% of US licensed physicians were at least 70 years old — more than 120,000 in total — up from 9% in a 2010, according to a Federation of State Medical Boards 2021 report.

Scripps Clinic Medical Group settled with the EEOC “without any admission of fault or wrongdoing to avoid the continued expense and distraction of litigation,” its statement said. It agreed to pay $6.875 million to the affected physicians.

When asked about how many physicians were affected by the policy, a Scripps human resources official said, “this was disputed but very few. The policy was only in effect for 2 years, 2016 and 2017. Additionally, by age 75, most doctors have retired. And those who have not almost always have voluntarily limited their practice.”

The Scripps official didn’t respond to questions about the number of patients served by the medical group and how many physicians it employs.

According to the EEOC, the medical group has agreed to tell employees that the policy has been scrapped and must “clarify that the company does not have any policy in which age is a factor in making employment decisions, including termination, retirement, and terms and conditions of employment.”

Scripps Clinic Medical Group also agreed to require division and department heads, executive leadership, and human resources employees to be trained regarding the Age Discrimination in Employment Act and the Americans with Disabilities Act.

A version of this article appeared on Medscape.com.

In a victory for clinicians who fought to keep working regardless of age, a San Diego–based medical group has agreed to settle a federal investigation by paying nearly $7 million to physicians subject to their employer’s policy requiring them to quit at age 75.

In a statement, the US Equal Employment Opportunity Commission (EEOC) said the settlement will resolve an age and disability discrimination charge filed against Scripps Clinic Medical Group. The medical group is part of Scripps Health, a major provider of medical services in the San Diego region that operates five local hospitals.

The EECO said it found “reasonable cause” that the medical group violated the Age Discrimination in Employment Act and the Americans with Disabilities Act.

US health systems are facing lawsuits that claim they’ve engaged in age discrimination by requiring physicians to take cognitive tests when they reach specific ages.

The Scripps medical group’s mandatory retirement policy began in 2016 and was consistent with California law, which specifically allows for mandatory retirement of physicians in medical groups at age 70, Scripps said in a statement, adding that it rescinded the policy in 2018.

“This policy was put in place to enhance patient safety,” Scripps said. “The EEOC took the position while such a policy is expressly legal under California law; it is not allowed under federal law.”

The Federal Age Discrimination in Employment Act, passed in 1967, states that employers may not “fail or refuse to hire or to discharge any individual or otherwise discriminate against any individual with respect to his compensation, terms, conditions, or privileges of employment because of such individual’s age.” There are exceptions, however, in cases of public safety for professions such as air traffic controllers.

California law has a similar provision banning age discrimination, but it makes an exception for “any employee who has attained 70 years of age and is a physician employed by a professional medical corporation, the articles or bylaws of which provide for compulsory retirement.”

In 2020, an estimated 12% of US licensed physicians were at least 70 years old — more than 120,000 in total — up from 9% in a 2010, according to a Federation of State Medical Boards 2021 report.

Scripps Clinic Medical Group settled with the EEOC “without any admission of fault or wrongdoing to avoid the continued expense and distraction of litigation,” its statement said. It agreed to pay $6.875 million to the affected physicians.

When asked about how many physicians were affected by the policy, a Scripps human resources official said, “this was disputed but very few. The policy was only in effect for 2 years, 2016 and 2017. Additionally, by age 75, most doctors have retired. And those who have not almost always have voluntarily limited their practice.”

The Scripps official didn’t respond to questions about the number of patients served by the medical group and how many physicians it employs.

According to the EEOC, the medical group has agreed to tell employees that the policy has been scrapped and must “clarify that the company does not have any policy in which age is a factor in making employment decisions, including termination, retirement, and terms and conditions of employment.”

Scripps Clinic Medical Group also agreed to require division and department heads, executive leadership, and human resources employees to be trained regarding the Age Discrimination in Employment Act and the Americans with Disabilities Act.

A version of this article appeared on Medscape.com.

SAN DIEGO — The average age of death for Black U.S. patients with sickle cell disease (SCD) rose from 39 years (females = 40, males = 38) in 1999-2009 to 43 years (females = 44, males = 41) in 2010-2020, reflecting improvements in treatment, a new study finds.

But the news is not all positive. Mortality rates still jumped markedly as patients transitioned from pediatric to adult care, lead author Kristine A. Karkoska, MD, a pediatric hematology/oncologist with the University of Cincinnati College of Medicine, said at the annual meeting of the American Society of Hematology.

“This reflects that young adults are getting lost to care, and then they’re presenting with acute, life-threatening complications,” she said. “We still need more emphasis on comprehensive lifetime sickle-cell care and the transition to adult clinics to improve mortality in young adults.”

According to Dr. Karkoska, researchers launched the analysis of sickle-cell mortality rates to update previously available data up to the year 2009, which showed improvements as current standard-of-care treatments were introduced. Updated numbers, she said, would reflect the influence of a rise in dedicated SCD clinics and a 2014 National Heart, Lung, and Blood Institute recommendation that all children with SCD be treated with hydroxyurea starting at 9 months.

For the study, Dr. Karkoska and colleagues analyzed mortality statistics from the period of 1979-2020 via a CDC database. They found that 5272 Black patients died of SCD from 2010 to 2020. The crude mortality rate was 1.1 per 100,000 Black people, lower than the 1.2 per 100,000 rate of 1999-2009 (P < .0001).

The researchers also found that from 2010 to 2020, the mortality rate jumped for patients in the 15-19 to 20-24 age group: It rose from 0.9 per 100,000 to 1.4 per 100,000, P < .0001).

The researchers also examined contributors to death other than SCD. In 39% of cases, underlying causes were noted: cardiovascular disease (28%), accidents (7%), cerebrovascular disease (7%), malignancy (6%), septicemia (4.8%), and renal disease (3.8%). The population of people with SCD is “getting older, and they’re developing a combination of both sickle-related chronic organ damage as well as non-sickle-related chronic disease,” Dr. Karkoska said.

She noted that limitations include a reliance on data that can be incomplete or inaccurate. She also mentioned that the study only focuses on Black patients, who make up the vast majority of those with SCD.

How good is the news about improved mortality numbers? One member of the audience at the ASH presentation was disappointed that they hadn’t gotten even better. “I was hoping to come here to be cheered up,” he said, “and I’m not.”

Three physicians who didn’t take part in the research but are familiar with the new study spoke in interviews about the findings.

Michael Bender, MD, PhD, director of the Odessa Brown Comprehensive Sickle Cell Clinic in Seattle, pointed out that mortality rates improve slowly over time, as new treatments enter the picture. When new therapies come along, he said, “it’s tough if someone’s already 40 years old and their body has gone through a lot. They’re not going to have as much benefit as someone who started [on therapy] when they were 5 years old, and they grew up with that improvement.”

Sickle cell specialist Asmaa Ferdjallah, MD, MPH, of the Mayo Clinic in Rochester, Minnesota, said that the data showing a spike in mortality rates during the pediatric-adult transition are not surprising but still “really hard to digest.”

“It is a testament to the fact that we are not meeting patients where they are,” she said. “We struggle immensely with the transition period. This is something that is difficult across all providers all over the country,” she said. “There are different ways to ensure a successful transition from the pediatric side to the adult side. Here at Mayo Clinic, we use a slow transition, and we rotate appointments with peds and adults until age 30.”

Sophie Miriam Lanzkron, MD, MHS, director of the Sickle Cell Center for Adults at Johns Hopkins Hospital, Baltimore, said increases in mortality in the post-pediatric period appear to be due in part to “lack of access to high-quality sickle cell care for adults because there aren’t enough hematologists.” Worsening disease due to aging is another factor, she said, and “there might also be some behavioral changes. Young people think they will live forever. Sometimes they choose not to adhere to medical recommendations, which for this population is very risky.”

Dr. Lanzkron said her team is developing a long-term patient registry that should provide more insight.

No study funding was reported. Dr. Karkoska had no disclosures. The other coauthor disclosed research funding and safety advisory board relationships with Novartis. Dr. Ferdjallah, Dr. Lanzkron, and Dr. Bender reported no disclosures.

SAN DIEGO — The average age of death for Black U.S. patients with sickle cell disease (SCD) rose from 39 years (females = 40, males = 38) in 1999-2009 to 43 years (females = 44, males = 41) in 2010-2020, reflecting improvements in treatment, a new study finds.

But the news is not all positive. Mortality rates still jumped markedly as patients transitioned from pediatric to adult care, lead author Kristine A. Karkoska, MD, a pediatric hematology/oncologist with the University of Cincinnati College of Medicine, said at the annual meeting of the American Society of Hematology.

“This reflects that young adults are getting lost to care, and then they’re presenting with acute, life-threatening complications,” she said. “We still need more emphasis on comprehensive lifetime sickle-cell care and the transition to adult clinics to improve mortality in young adults.”

According to Dr. Karkoska, researchers launched the analysis of sickle-cell mortality rates to update previously available data up to the year 2009, which showed improvements as current standard-of-care treatments were introduced. Updated numbers, she said, would reflect the influence of a rise in dedicated SCD clinics and a 2014 National Heart, Lung, and Blood Institute recommendation that all children with SCD be treated with hydroxyurea starting at 9 months.

For the study, Dr. Karkoska and colleagues analyzed mortality statistics from the period of 1979-2020 via a CDC database. They found that 5272 Black patients died of SCD from 2010 to 2020. The crude mortality rate was 1.1 per 100,000 Black people, lower than the 1.2 per 100,000 rate of 1999-2009 (P < .0001).

The researchers also found that from 2010 to 2020, the mortality rate jumped for patients in the 15-19 to 20-24 age group: It rose from 0.9 per 100,000 to 1.4 per 100,000, P < .0001).

The researchers also examined contributors to death other than SCD. In 39% of cases, underlying causes were noted: cardiovascular disease (28%), accidents (7%), cerebrovascular disease (7%), malignancy (6%), septicemia (4.8%), and renal disease (3.8%). The population of people with SCD is “getting older, and they’re developing a combination of both sickle-related chronic organ damage as well as non-sickle-related chronic disease,” Dr. Karkoska said.

She noted that limitations include a reliance on data that can be incomplete or inaccurate. She also mentioned that the study only focuses on Black patients, who make up the vast majority of those with SCD.

How good is the news about improved mortality numbers? One member of the audience at the ASH presentation was disappointed that they hadn’t gotten even better. “I was hoping to come here to be cheered up,” he said, “and I’m not.”

Three physicians who didn’t take part in the research but are familiar with the new study spoke in interviews about the findings.

Michael Bender, MD, PhD, director of the Odessa Brown Comprehensive Sickle Cell Clinic in Seattle, pointed out that mortality rates improve slowly over time, as new treatments enter the picture. When new therapies come along, he said, “it’s tough if someone’s already 40 years old and their body has gone through a lot. They’re not going to have as much benefit as someone who started [on therapy] when they were 5 years old, and they grew up with that improvement.”

Sickle cell specialist Asmaa Ferdjallah, MD, MPH, of the Mayo Clinic in Rochester, Minnesota, said that the data showing a spike in mortality rates during the pediatric-adult transition are not surprising but still “really hard to digest.”

“It is a testament to the fact that we are not meeting patients where they are,” she said. “We struggle immensely with the transition period. This is something that is difficult across all providers all over the country,” she said. “There are different ways to ensure a successful transition from the pediatric side to the adult side. Here at Mayo Clinic, we use a slow transition, and we rotate appointments with peds and adults until age 30.”

Sophie Miriam Lanzkron, MD, MHS, director of the Sickle Cell Center for Adults at Johns Hopkins Hospital, Baltimore, said increases in mortality in the post-pediatric period appear to be due in part to “lack of access to high-quality sickle cell care for adults because there aren’t enough hematologists.” Worsening disease due to aging is another factor, she said, and “there might also be some behavioral changes. Young people think they will live forever. Sometimes they choose not to adhere to medical recommendations, which for this population is very risky.”

Dr. Lanzkron said her team is developing a long-term patient registry that should provide more insight.

No study funding was reported. Dr. Karkoska had no disclosures. The other coauthor disclosed research funding and safety advisory board relationships with Novartis. Dr. Ferdjallah, Dr. Lanzkron, and Dr. Bender reported no disclosures.

SAN DIEGO — The average age of death for Black U.S. patients with sickle cell disease (SCD) rose from 39 years (females = 40, males = 38) in 1999-2009 to 43 years (females = 44, males = 41) in 2010-2020, reflecting improvements in treatment, a new study finds.

But the news is not all positive. Mortality rates still jumped markedly as patients transitioned from pediatric to adult care, lead author Kristine A. Karkoska, MD, a pediatric hematology/oncologist with the University of Cincinnati College of Medicine, said at the annual meeting of the American Society of Hematology.

“This reflects that young adults are getting lost to care, and then they’re presenting with acute, life-threatening complications,” she said. “We still need more emphasis on comprehensive lifetime sickle-cell care and the transition to adult clinics to improve mortality in young adults.”

According to Dr. Karkoska, researchers launched the analysis of sickle-cell mortality rates to update previously available data up to the year 2009, which showed improvements as current standard-of-care treatments were introduced. Updated numbers, she said, would reflect the influence of a rise in dedicated SCD clinics and a 2014 National Heart, Lung, and Blood Institute recommendation that all children with SCD be treated with hydroxyurea starting at 9 months.

For the study, Dr. Karkoska and colleagues analyzed mortality statistics from the period of 1979-2020 via a CDC database. They found that 5272 Black patients died of SCD from 2010 to 2020. The crude mortality rate was 1.1 per 100,000 Black people, lower than the 1.2 per 100,000 rate of 1999-2009 (P < .0001).

The researchers also found that from 2010 to 2020, the mortality rate jumped for patients in the 15-19 to 20-24 age group: It rose from 0.9 per 100,000 to 1.4 per 100,000, P < .0001).

The researchers also examined contributors to death other than SCD. In 39% of cases, underlying causes were noted: cardiovascular disease (28%), accidents (7%), cerebrovascular disease (7%), malignancy (6%), septicemia (4.8%), and renal disease (3.8%). The population of people with SCD is “getting older, and they’re developing a combination of both sickle-related chronic organ damage as well as non-sickle-related chronic disease,” Dr. Karkoska said.

She noted that limitations include a reliance on data that can be incomplete or inaccurate. She also mentioned that the study only focuses on Black patients, who make up the vast majority of those with SCD.

How good is the news about improved mortality numbers? One member of the audience at the ASH presentation was disappointed that they hadn’t gotten even better. “I was hoping to come here to be cheered up,” he said, “and I’m not.”

Three physicians who didn’t take part in the research but are familiar with the new study spoke in interviews about the findings.

Michael Bender, MD, PhD, director of the Odessa Brown Comprehensive Sickle Cell Clinic in Seattle, pointed out that mortality rates improve slowly over time, as new treatments enter the picture. When new therapies come along, he said, “it’s tough if someone’s already 40 years old and their body has gone through a lot. They’re not going to have as much benefit as someone who started [on therapy] when they were 5 years old, and they grew up with that improvement.”

Sickle cell specialist Asmaa Ferdjallah, MD, MPH, of the Mayo Clinic in Rochester, Minnesota, said that the data showing a spike in mortality rates during the pediatric-adult transition are not surprising but still “really hard to digest.”

“It is a testament to the fact that we are not meeting patients where they are,” she said. “We struggle immensely with the transition period. This is something that is difficult across all providers all over the country,” she said. “There are different ways to ensure a successful transition from the pediatric side to the adult side. Here at Mayo Clinic, we use a slow transition, and we rotate appointments with peds and adults until age 30.”

Sophie Miriam Lanzkron, MD, MHS, director of the Sickle Cell Center for Adults at Johns Hopkins Hospital, Baltimore, said increases in mortality in the post-pediatric period appear to be due in part to “lack of access to high-quality sickle cell care for adults because there aren’t enough hematologists.” Worsening disease due to aging is another factor, she said, and “there might also be some behavioral changes. Young people think they will live forever. Sometimes they choose not to adhere to medical recommendations, which for this population is very risky.”

Dr. Lanzkron said her team is developing a long-term patient registry that should provide more insight.

No study funding was reported. Dr. Karkoska had no disclosures. The other coauthor disclosed research funding and safety advisory board relationships with Novartis. Dr. Ferdjallah, Dr. Lanzkron, and Dr. Bender reported no disclosures.

SAN DIEGO — A small group of adult and pediatric patients with sickle cell disease (SCD) reached high 2-year survival after undergoing reduced-intensity haploidentical stem cell transplantation, a new phase 2 trial reports. It is much easier to find eligible haploidentical donors — half-matched or partially matched — than eligible hematopoietic donors.

Of 42 patients aged 15-45 who were fully treated, 95% survived to 2 years post transplant (overall survival, (95% CI, 81.5%-98.7%), and 88% reached the primary endpoint of event-free survival at 2 years (95% CI, 73.5%-94.8%), according to the findings, which were released at the annual meeting of the American Society of Hematology.

At an ASH news briefing, study lead author Adetola A. Kassim, MBBS, MS, of Vanderbilt University Medical Center, in Nashville, Tennessee, said the results support haploidentical stem cell transplants “as a suitable and tolerable curative therapy for adults with sickle cell disease and severe end-organ toxicity such as stroke or pulmonary hypertension, a population typically excluded from participating in gene therapy.”

Dr. Kassim added that the findings are especially promising since there are so many potential donors in stem-cell transplants: “Your siblings can be donors, your parents can be donors, your cousins can be donors. First-, second-, and third-degree relatives can be donors. So there’s really endless donors within the family.”

In an interview, Mayo Clinic SCD specialist Asmaa Ferdjallah, MD, MPH, of Mayo Clinic in Rochester, Minnesota, who was not involved with the study but is familiar with its findings, said stem cell transplant is the only option to cure SCD.

“This is advantageous because SCD is otherwise a chronic disease that is marked by chronic pain, risk of stroke, frequent interruptions of school/work due to sick days, and decreased life span,” she said. “Most patients, assuming they can tolerate the conditioning chemotherapy that is given before transplant, are eligible.”

Matched sibling donors are preferable, but they can be hard to find, she said. It hasn’t been clear whether half-matched donors are feasible options in SCD, she said. “This means that, if you are a patient with sickle cell disease, and you don’t have a suitable matched donor, haploidentical transplant is not a recommendation we can make outside of enrollment in a clinical trial.”

For the study, researchers enlisted 54 patients with SCD and prior stroke, recurrent acute chest syndrome or pain, chronic transfusion regimen, or tricuspid valve regurgitant jet velocity ≥2.7 m/sec. Participants had to have an HLA-haploidentical first-degree relative donor who would donate bone marrow.

“The median age was 22.8 years at enrollment; 47/54 (87%) of enrolled participants had hemoglobin SS disease, 40/54 (74.1%) had a Lansky/Karnofsky score of 90-100 at baseline, and 41/54 (75.9%) had an HLA match score of 4/8,” the researchers reported. “Recurrent vaso-occlusive pain episodes (38.9%), acute chest syndrome (16.8%), and overt stroke (16.7%) were the most common indications for transplant.”

“We knew going into this that we were going to get very high-risk patients,” Dr. Kassim said.

Forty-two patients went through with transplants. As for adverse events, 2 patients died, all within the first year, of organ failure and acute respiratory distress syndrome; 4.8% of participants had primary graft failure, and 2.4% had secondary graft failure before day 100. “The cumulative incidence of grades II-IV acute GVHD [graft-versus-host disease] at day 100 was 26.2% (95% CI, 14.0%-40.2%), and grades III-IV acute GVHD at day 100 was 4.8% (95% CI, 0.9%-14.4%).”

The outcomes are similar to those in transplants with matched sibling donors, Dr. Kassim said.

Dr. Ferdjallah said the new study is “robust” and impressive, although it’s small.

“As a clinician, these are the kind of outcomes I have been hoping for,” Dr. Ferdjallah said. “I have been very reluctant to suggest haploidentical transplant for my sickle cell disease patients. However, reviewing the results of this study with my motivated patients and families can help us both to use shared medical decision-making and come together with what is best for that specific patient.”

As for adverse events, she said they “confirm a fear of using haploidentical transplant, which is graft failure. Fortunately, out of 42 who proceeded to transplant, only 2 had primary graft failure and 1 had secondary graft failure. This is not overtly a large number. Of course, we would hope for more durable engraftment. The other side effects including GVHD and infection are all to be expected.”

As for cost, Dr. Kassim said the transplants run from $200,000 to $400,000 vs over $2 million for gene therapy, and Dr. Ferdjallah said insurance is likely to cover the treatment.

Moving ahead, Dr. Ferdjallah said she looks forward to getting study data about pediatric patients specifically. For now, “we should consider HLA-haploidentical seriously in patients with sickle cell disease and no available HLA-matched donors.”

Grants to the Blood and Marrow Transplant Clinical Trials Network from the National Heart, Lung, and Blood Institute and National Cancer Institute funded the study. Dr. Kassim had no disclosures. Some other authors disclosed various and multiple relationships with industry. Dr. Ferdjallah has no disclosures.

SAN DIEGO — A small group of adult and pediatric patients with sickle cell disease (SCD) reached high 2-year survival after undergoing reduced-intensity haploidentical stem cell transplantation, a new phase 2 trial reports. It is much easier to find eligible haploidentical donors — half-matched or partially matched — than eligible hematopoietic donors.

Of 42 patients aged 15-45 who were fully treated, 95% survived to 2 years post transplant (overall survival, (95% CI, 81.5%-98.7%), and 88% reached the primary endpoint of event-free survival at 2 years (95% CI, 73.5%-94.8%), according to the findings, which were released at the annual meeting of the American Society of Hematology.

At an ASH news briefing, study lead author Adetola A. Kassim, MBBS, MS, of Vanderbilt University Medical Center, in Nashville, Tennessee, said the results support haploidentical stem cell transplants “as a suitable and tolerable curative therapy for adults with sickle cell disease and severe end-organ toxicity such as stroke or pulmonary hypertension, a population typically excluded from participating in gene therapy.”

Dr. Kassim added that the findings are especially promising since there are so many potential donors in stem-cell transplants: “Your siblings can be donors, your parents can be donors, your cousins can be donors. First-, second-, and third-degree relatives can be donors. So there’s really endless donors within the family.”

In an interview, Mayo Clinic SCD specialist Asmaa Ferdjallah, MD, MPH, of Mayo Clinic in Rochester, Minnesota, who was not involved with the study but is familiar with its findings, said stem cell transplant is the only option to cure SCD.

“This is advantageous because SCD is otherwise a chronic disease that is marked by chronic pain, risk of stroke, frequent interruptions of school/work due to sick days, and decreased life span,” she said. “Most patients, assuming they can tolerate the conditioning chemotherapy that is given before transplant, are eligible.”

Matched sibling donors are preferable, but they can be hard to find, she said. It hasn’t been clear whether half-matched donors are feasible options in SCD, she said. “This means that, if you are a patient with sickle cell disease, and you don’t have a suitable matched donor, haploidentical transplant is not a recommendation we can make outside of enrollment in a clinical trial.”

For the study, researchers enlisted 54 patients with SCD and prior stroke, recurrent acute chest syndrome or pain, chronic transfusion regimen, or tricuspid valve regurgitant jet velocity ≥2.7 m/sec. Participants had to have an HLA-haploidentical first-degree relative donor who would donate bone marrow.

“The median age was 22.8 years at enrollment; 47/54 (87%) of enrolled participants had hemoglobin SS disease, 40/54 (74.1%) had a Lansky/Karnofsky score of 90-100 at baseline, and 41/54 (75.9%) had an HLA match score of 4/8,” the researchers reported. “Recurrent vaso-occlusive pain episodes (38.9%), acute chest syndrome (16.8%), and overt stroke (16.7%) were the most common indications for transplant.”

“We knew going into this that we were going to get very high-risk patients,” Dr. Kassim said.

Forty-two patients went through with transplants. As for adverse events, 2 patients died, all within the first year, of organ failure and acute respiratory distress syndrome; 4.8% of participants had primary graft failure, and 2.4% had secondary graft failure before day 100. “The cumulative incidence of grades II-IV acute GVHD [graft-versus-host disease] at day 100 was 26.2% (95% CI, 14.0%-40.2%), and grades III-IV acute GVHD at day 100 was 4.8% (95% CI, 0.9%-14.4%).”

The outcomes are similar to those in transplants with matched sibling donors, Dr. Kassim said.

Dr. Ferdjallah said the new study is “robust” and impressive, although it’s small.

“As a clinician, these are the kind of outcomes I have been hoping for,” Dr. Ferdjallah said. “I have been very reluctant to suggest haploidentical transplant for my sickle cell disease patients. However, reviewing the results of this study with my motivated patients and families can help us both to use shared medical decision-making and come together with what is best for that specific patient.”

As for adverse events, she said they “confirm a fear of using haploidentical transplant, which is graft failure. Fortunately, out of 42 who proceeded to transplant, only 2 had primary graft failure and 1 had secondary graft failure. This is not overtly a large number. Of course, we would hope for more durable engraftment. The other side effects including GVHD and infection are all to be expected.”

As for cost, Dr. Kassim said the transplants run from $200,000 to $400,000 vs over $2 million for gene therapy, and Dr. Ferdjallah said insurance is likely to cover the treatment.

Moving ahead, Dr. Ferdjallah said she looks forward to getting study data about pediatric patients specifically. For now, “we should consider HLA-haploidentical seriously in patients with sickle cell disease and no available HLA-matched donors.”

Grants to the Blood and Marrow Transplant Clinical Trials Network from the National Heart, Lung, and Blood Institute and National Cancer Institute funded the study. Dr. Kassim had no disclosures. Some other authors disclosed various and multiple relationships with industry. Dr. Ferdjallah has no disclosures.

SAN DIEGO — A small group of adult and pediatric patients with sickle cell disease (SCD) reached high 2-year survival after undergoing reduced-intensity haploidentical stem cell transplantation, a new phase 2 trial reports. It is much easier to find eligible haploidentical donors — half-matched or partially matched — than eligible hematopoietic donors.

Of 42 patients aged 15-45 who were fully treated, 95% survived to 2 years post transplant (overall survival, (95% CI, 81.5%-98.7%), and 88% reached the primary endpoint of event-free survival at 2 years (95% CI, 73.5%-94.8%), according to the findings, which were released at the annual meeting of the American Society of Hematology.

At an ASH news briefing, study lead author Adetola A. Kassim, MBBS, MS, of Vanderbilt University Medical Center, in Nashville, Tennessee, said the results support haploidentical stem cell transplants “as a suitable and tolerable curative therapy for adults with sickle cell disease and severe end-organ toxicity such as stroke or pulmonary hypertension, a population typically excluded from participating in gene therapy.”

Dr. Kassim added that the findings are especially promising since there are so many potential donors in stem-cell transplants: “Your siblings can be donors, your parents can be donors, your cousins can be donors. First-, second-, and third-degree relatives can be donors. So there’s really endless donors within the family.”

In an interview, Mayo Clinic SCD specialist Asmaa Ferdjallah, MD, MPH, of Mayo Clinic in Rochester, Minnesota, who was not involved with the study but is familiar with its findings, said stem cell transplant is the only option to cure SCD.

“This is advantageous because SCD is otherwise a chronic disease that is marked by chronic pain, risk of stroke, frequent interruptions of school/work due to sick days, and decreased life span,” she said. “Most patients, assuming they can tolerate the conditioning chemotherapy that is given before transplant, are eligible.”

Matched sibling donors are preferable, but they can be hard to find, she said. It hasn’t been clear whether half-matched donors are feasible options in SCD, she said. “This means that, if you are a patient with sickle cell disease, and you don’t have a suitable matched donor, haploidentical transplant is not a recommendation we can make outside of enrollment in a clinical trial.”

For the study, researchers enlisted 54 patients with SCD and prior stroke, recurrent acute chest syndrome or pain, chronic transfusion regimen, or tricuspid valve regurgitant jet velocity ≥2.7 m/sec. Participants had to have an HLA-haploidentical first-degree relative donor who would donate bone marrow.

“The median age was 22.8 years at enrollment; 47/54 (87%) of enrolled participants had hemoglobin SS disease, 40/54 (74.1%) had a Lansky/Karnofsky score of 90-100 at baseline, and 41/54 (75.9%) had an HLA match score of 4/8,” the researchers reported. “Recurrent vaso-occlusive pain episodes (38.9%), acute chest syndrome (16.8%), and overt stroke (16.7%) were the most common indications for transplant.”

“We knew going into this that we were going to get very high-risk patients,” Dr. Kassim said.

Forty-two patients went through with transplants. As for adverse events, 2 patients died, all within the first year, of organ failure and acute respiratory distress syndrome; 4.8% of participants had primary graft failure, and 2.4% had secondary graft failure before day 100. “The cumulative incidence of grades II-IV acute GVHD [graft-versus-host disease] at day 100 was 26.2% (95% CI, 14.0%-40.2%), and grades III-IV acute GVHD at day 100 was 4.8% (95% CI, 0.9%-14.4%).”

The outcomes are similar to those in transplants with matched sibling donors, Dr. Kassim said.

Dr. Ferdjallah said the new study is “robust” and impressive, although it’s small.

“As a clinician, these are the kind of outcomes I have been hoping for,” Dr. Ferdjallah said. “I have been very reluctant to suggest haploidentical transplant for my sickle cell disease patients. However, reviewing the results of this study with my motivated patients and families can help us both to use shared medical decision-making and come together with what is best for that specific patient.”

As for adverse events, she said they “confirm a fear of using haploidentical transplant, which is graft failure. Fortunately, out of 42 who proceeded to transplant, only 2 had primary graft failure and 1 had secondary graft failure. This is not overtly a large number. Of course, we would hope for more durable engraftment. The other side effects including GVHD and infection are all to be expected.”

As for cost, Dr. Kassim said the transplants run from $200,000 to $400,000 vs over $2 million for gene therapy, and Dr. Ferdjallah said insurance is likely to cover the treatment.

Moving ahead, Dr. Ferdjallah said she looks forward to getting study data about pediatric patients specifically. For now, “we should consider HLA-haploidentical seriously in patients with sickle cell disease and no available HLA-matched donors.”

Grants to the Blood and Marrow Transplant Clinical Trials Network from the National Heart, Lung, and Blood Institute and National Cancer Institute funded the study. Dr. Kassim had no disclosures. Some other authors disclosed various and multiple relationships with industry. Dr. Ferdjallah has no disclosures.

SAN DIEGO — Median progression-free survival (PFS) improved by about 10 months in patients with relapsed/refractory mantle cell lymphoma (MCL) who were treated with both ibrutinib (Imbruvica) and venetoclax (Venclexta) vs. ibrutinib alone, an interim analysis of a new study finds. However, there was a statistically significant difference in overall survival between the groups.

Still, “in the countries where ibrutinib is indicated, this combination should be a new standard therapy for relapsed/refractory mantle cell lymphoma,” Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in a media briefing at the annual meeting of the American Society of Hematology.

Its use would be off label, according to the authors of the industry-funded trial, because no nation has approved the combination therapy for MCL, a rare, aggressive form of non-Hodgkin lymphoma.

As Dr. Wang noted, ibrutinib (a Bruton tyrosine kinase inhibitor) is approved by the Food and Drug Administration to treat MCL, while venetoclax (a BCL-2 inhibitor) is approved for chronic lymphocytic leukemia and previously untreated acute myeloid leukemia. “The combination of these two agents leverages complementary modes of action and has demonstrated synergistic anti-tumor activity in preclinical models of mantle cell lymphoma,” he said. And “in patients with relapsed/refractory mantle cell lymphoma, promising clinical activity has also been observed in early-phase studies.”

For the multinational, randomized, phase 3, double-blind SYMPATICO study, researchers assigned 267 adults with relapsed/refractory MCL after 1-5 prior therapies 1:1 to receive oral ibrutinib 560 mg daily with oral venetoclax (standard 5-wk ramp-up to a target dose of 400 mg once daily) or placebo for 2 years. Then they continued with ibrutinib alone until progressive disease or unacceptable toxicity.

The study began in 2017. The median age of patients was 68, and the numbers of patients in each group were 134 (both drugs) and 133 (ibrutinib plus placebo).

At a median of 51.2 months, median PFS — the primary endpoint — was higher in the combination group vs. ibrutinib alone (31.9 vs. 22.1 months, hazard ratio [HR]=0.65, 95% CI, 0.47–0.88, P = .0052). While overall survival was higher in the combination group vs. ibrutinib alone, an interim analysis found that the difference was not statistically significant (44.9 months vs. 38.6 months, 95% CI, HR = 0.85, 0.62-1.19, P = .3465).

When questioned about this finding at the ASH news briefing, Dr. Wang said that 170 events are needed for a full overall survival analysis, and there are just 144 now. The study may reach that point in early 2025, he said.

Over a median treatment duration of 22.0 months for the combination treatment and 17.7 months for ibrutinib alone, grade ≥ 3 adverse events occurred in 84% and 76% of patients, respectively. At 60%, the level of serious adverse events was the same in both groups.

In an interview, Brian T. Hill, MD, PhD, of Cleveland Clinic, noted that in general, MCL “has a pretty relentless pattern of relapses and disease progression without an easy cure in the vast majority of patients.”

Ibrutinib has revolutionized treatment over the past decade with generally manageable side effects, and clinicians are now turning to other Bruton tyrosine kinase inhibitors, he said. Still, “there is a need for improving the durability and the response rates second-line treatment or beyond,” Dr. Hill said.

The new study is important since it’s the first randomized trial “that demonstrates that additional venetoclax significantly improves not only response rates, but also progression-free survival with a trend toward overall survival,” he said. “The toxicity profile doesn’t really seem to be significantly more worse than what we might expect with each agent given individually.”

However, Dr. Hill noted that “it’s a relatively small study and relatively short follow-up.”

It may be difficult to get an ibrutinib-venetoclax combination approved today since ibrutinib is no longer the preferred Bruton tyrosine kinase inhibitor for clinicians, he said.

Pharmacyclics, maker of ibrutinib, is the study sponsor and Janssen is a collaborator.

Dr. Wang reports research funding Acerta Pharma, AstraZeneca, BeiGene, BioInvent, Celgene, Genentech, Innocare, Janssen, Juno Therapeutics, Kite Pharma, Lilly, Loxo Oncology, Molecular Templates, Oncternal, Pharmacyclics, and VelosBio. Other authors report multiple and various relationships with industry. Dr. Hill discloses research funding and consulting relationships with Pharmacyclics, AbbVie, BeiGene, and AstraZeneca.

SAN DIEGO — Median progression-free survival (PFS) improved by about 10 months in patients with relapsed/refractory mantle cell lymphoma (MCL) who were treated with both ibrutinib (Imbruvica) and venetoclax (Venclexta) vs. ibrutinib alone, an interim analysis of a new study finds. However, there was a statistically significant difference in overall survival between the groups.

Still, “in the countries where ibrutinib is indicated, this combination should be a new standard therapy for relapsed/refractory mantle cell lymphoma,” Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in a media briefing at the annual meeting of the American Society of Hematology.

Its use would be off label, according to the authors of the industry-funded trial, because no nation has approved the combination therapy for MCL, a rare, aggressive form of non-Hodgkin lymphoma.

As Dr. Wang noted, ibrutinib (a Bruton tyrosine kinase inhibitor) is approved by the Food and Drug Administration to treat MCL, while venetoclax (a BCL-2 inhibitor) is approved for chronic lymphocytic leukemia and previously untreated acute myeloid leukemia. “The combination of these two agents leverages complementary modes of action and has demonstrated synergistic anti-tumor activity in preclinical models of mantle cell lymphoma,” he said. And “in patients with relapsed/refractory mantle cell lymphoma, promising clinical activity has also been observed in early-phase studies.”

For the multinational, randomized, phase 3, double-blind SYMPATICO study, researchers assigned 267 adults with relapsed/refractory MCL after 1-5 prior therapies 1:1 to receive oral ibrutinib 560 mg daily with oral venetoclax (standard 5-wk ramp-up to a target dose of 400 mg once daily) or placebo for 2 years. Then they continued with ibrutinib alone until progressive disease or unacceptable toxicity.

The study began in 2017. The median age of patients was 68, and the numbers of patients in each group were 134 (both drugs) and 133 (ibrutinib plus placebo).

At a median of 51.2 months, median PFS — the primary endpoint — was higher in the combination group vs. ibrutinib alone (31.9 vs. 22.1 months, hazard ratio [HR]=0.65, 95% CI, 0.47–0.88, P = .0052). While overall survival was higher in the combination group vs. ibrutinib alone, an interim analysis found that the difference was not statistically significant (44.9 months vs. 38.6 months, 95% CI, HR = 0.85, 0.62-1.19, P = .3465).

When questioned about this finding at the ASH news briefing, Dr. Wang said that 170 events are needed for a full overall survival analysis, and there are just 144 now. The study may reach that point in early 2025, he said.

Over a median treatment duration of 22.0 months for the combination treatment and 17.7 months for ibrutinib alone, grade ≥ 3 adverse events occurred in 84% and 76% of patients, respectively. At 60%, the level of serious adverse events was the same in both groups.

In an interview, Brian T. Hill, MD, PhD, of Cleveland Clinic, noted that in general, MCL “has a pretty relentless pattern of relapses and disease progression without an easy cure in the vast majority of patients.”

Ibrutinib has revolutionized treatment over the past decade with generally manageable side effects, and clinicians are now turning to other Bruton tyrosine kinase inhibitors, he said. Still, “there is a need for improving the durability and the response rates second-line treatment or beyond,” Dr. Hill said.

The new study is important since it’s the first randomized trial “that demonstrates that additional venetoclax significantly improves not only response rates, but also progression-free survival with a trend toward overall survival,” he said. “The toxicity profile doesn’t really seem to be significantly more worse than what we might expect with each agent given individually.”

However, Dr. Hill noted that “it’s a relatively small study and relatively short follow-up.”

It may be difficult to get an ibrutinib-venetoclax combination approved today since ibrutinib is no longer the preferred Bruton tyrosine kinase inhibitor for clinicians, he said.

Pharmacyclics, maker of ibrutinib, is the study sponsor and Janssen is a collaborator.

Dr. Wang reports research funding Acerta Pharma, AstraZeneca, BeiGene, BioInvent, Celgene, Genentech, Innocare, Janssen, Juno Therapeutics, Kite Pharma, Lilly, Loxo Oncology, Molecular Templates, Oncternal, Pharmacyclics, and VelosBio. Other authors report multiple and various relationships with industry. Dr. Hill discloses research funding and consulting relationships with Pharmacyclics, AbbVie, BeiGene, and AstraZeneca.

SAN DIEGO — Median progression-free survival (PFS) improved by about 10 months in patients with relapsed/refractory mantle cell lymphoma (MCL) who were treated with both ibrutinib (Imbruvica) and venetoclax (Venclexta) vs. ibrutinib alone, an interim analysis of a new study finds. However, there was a statistically significant difference in overall survival between the groups.

Still, “in the countries where ibrutinib is indicated, this combination should be a new standard therapy for relapsed/refractory mantle cell lymphoma,” Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in a media briefing at the annual meeting of the American Society of Hematology.

Its use would be off label, according to the authors of the industry-funded trial, because no nation has approved the combination therapy for MCL, a rare, aggressive form of non-Hodgkin lymphoma.

As Dr. Wang noted, ibrutinib (a Bruton tyrosine kinase inhibitor) is approved by the Food and Drug Administration to treat MCL, while venetoclax (a BCL-2 inhibitor) is approved for chronic lymphocytic leukemia and previously untreated acute myeloid leukemia. “The combination of these two agents leverages complementary modes of action and has demonstrated synergistic anti-tumor activity in preclinical models of mantle cell lymphoma,” he said. And “in patients with relapsed/refractory mantle cell lymphoma, promising clinical activity has also been observed in early-phase studies.”

For the multinational, randomized, phase 3, double-blind SYMPATICO study, researchers assigned 267 adults with relapsed/refractory MCL after 1-5 prior therapies 1:1 to receive oral ibrutinib 560 mg daily with oral venetoclax (standard 5-wk ramp-up to a target dose of 400 mg once daily) or placebo for 2 years. Then they continued with ibrutinib alone until progressive disease or unacceptable toxicity.

The study began in 2017. The median age of patients was 68, and the numbers of patients in each group were 134 (both drugs) and 133 (ibrutinib plus placebo).

At a median of 51.2 months, median PFS — the primary endpoint — was higher in the combination group vs. ibrutinib alone (31.9 vs. 22.1 months, hazard ratio [HR]=0.65, 95% CI, 0.47–0.88, P = .0052). While overall survival was higher in the combination group vs. ibrutinib alone, an interim analysis found that the difference was not statistically significant (44.9 months vs. 38.6 months, 95% CI, HR = 0.85, 0.62-1.19, P = .3465).

When questioned about this finding at the ASH news briefing, Dr. Wang said that 170 events are needed for a full overall survival analysis, and there are just 144 now. The study may reach that point in early 2025, he said.

Over a median treatment duration of 22.0 months for the combination treatment and 17.7 months for ibrutinib alone, grade ≥ 3 adverse events occurred in 84% and 76% of patients, respectively. At 60%, the level of serious adverse events was the same in both groups.

In an interview, Brian T. Hill, MD, PhD, of Cleveland Clinic, noted that in general, MCL “has a pretty relentless pattern of relapses and disease progression without an easy cure in the vast majority of patients.”

Ibrutinib has revolutionized treatment over the past decade with generally manageable side effects, and clinicians are now turning to other Bruton tyrosine kinase inhibitors, he said. Still, “there is a need for improving the durability and the response rates second-line treatment or beyond,” Dr. Hill said.

The new study is important since it’s the first randomized trial “that demonstrates that additional venetoclax significantly improves not only response rates, but also progression-free survival with a trend toward overall survival,” he said. “The toxicity profile doesn’t really seem to be significantly more worse than what we might expect with each agent given individually.”

However, Dr. Hill noted that “it’s a relatively small study and relatively short follow-up.”

It may be difficult to get an ibrutinib-venetoclax combination approved today since ibrutinib is no longer the preferred Bruton tyrosine kinase inhibitor for clinicians, he said.

Pharmacyclics, maker of ibrutinib, is the study sponsor and Janssen is a collaborator.

Dr. Wang reports research funding Acerta Pharma, AstraZeneca, BeiGene, BioInvent, Celgene, Genentech, Innocare, Janssen, Juno Therapeutics, Kite Pharma, Lilly, Loxo Oncology, Molecular Templates, Oncternal, Pharmacyclics, and VelosBio. Other authors report multiple and various relationships with industry. Dr. Hill discloses research funding and consulting relationships with Pharmacyclics, AbbVie, BeiGene, and AstraZeneca.

SAN DIEGO — In the real world, outcomes for patients with multiple myeloma who received standard regimens were dramatically worse than those reported in clinical trials, a new study found. 

The analysis, which included nearly 4,000 patients with multiple myeloma, revealed that patients in a real-world setting demonstrated worse progression-free and overall survival on six of seven standard treatments compared with patients evaluated in randomized controlled trials.

Lead author Alissa Visram, MD, MPH, who spoke about the study at the annual meeting of the American Society of Hematology, said the findings will likely change the way she speaks to patients about their potential outcomes. 

“I’ll probably present both numbers [from real-life and clinical-trial data] and give them a sense of the best-case scenario,” Dr. Visram said during an ASH media briefing. But she said she will also caution her patients that the real-world numbers reflect how people on these drugs actually fare. 

The effectiveness of multiple myeloma drugs remains unclear outside the clinical trial setting, explained Dr. Visram, of the Division of Hematology at the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. Outcomes from randomized controlled trials form the basis of drug approvals but many patients in the real world do not meet the “stringent” trial inclusion criteria. 

Dr. Visram and colleagues launched the current study to better understand the potential differences between real-world and clinical trial outcomes. In the analysis, the researchers compared real-world outcomes among patients receiving seven standard multiple myeloma regimens covered by Ontario’s public health plan with patient outcomes reported in phase 3 randomized controlled trials. 

The retrospective study included 3951 patients with newly diagnosed and refractory multiple myeloma treated from 2007 to 2020 in Ontario. Regimens for newly diagnosed transplant ineligible patients included lenalidomide plus dexamethasone and triple therapy with bortezomib, lenalidomide, and dexamethasone. Regimens for patients with relapsed disease included pomalidomide plus dexamethasone or carfilzomib plus dexamethasone as well as triple combinations including carfilzomib, lenalidomide, and dexamethasone.

Overall, Dr. Visram and colleagues found that patients in the real-world setting demonstrated worse overall survival for six of the seven regimens evaluated (pooled hazard ratio [HR], 1.75; P = .010). 

The real-world patients also had worse progression-free survival for six of the seven regimens (pooled HR, 1.44; P = .034). 

For these regimens, progression-free survival was at least 3-18 months longer in the clinical trial cohort, while median overall survival was at least 19 months longer compared with real-world patients, Dr. Visram explained. 

The only regimen with comparable outcomes in the clinical trial and real-world settings was pomalidomide and dexamethasone, she said. One reason could be that patients receiving pomalidomide plus dexamethasone in the clinical trial setting had similar or more advanced disease than those in the real-world setting.

The study also found that adverse effects were similar between the clinical and real-world groups. 

The next step, Dr. Visram said, would be to explore what’s driving the differences in outcomes. 

Are patients in the real-world setting older or frailer? Do they have more advanced disease? Are providers using these regimens differently? 

Mikkael A. Sekeres, MD, MS, explained that the difference likely comes down to the health of the patient. 

Patients in these types of clinical trials “are just these pristine specimens of human beings except for the cancer that’s being treated,” Dr. Sekeres, of the Sylvester Comprehensive Cancer Center at the University of Miami, Florida, said in an earlier ASH press briefing.

Cynthia E. Dunbar, MD, noted that patients in clinical trials have other advantages as well.

“Patients who are able to enroll in clinical trials are more likely to be able to show up at the treatment center at the right time and for every dose, have transportation, and afford drugs to prevent side effects,” said Dr. Dunbar, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute and secretary of ASH. These patients also “might stay on the drug for longer, or they have nurses who are always encouraging them on how to make it through a toxicity.”

Dr. Dunbar said hematologists and patients should consider randomized controlled trials to be “the best possible outcome, and perhaps adjust their thinking if an individual patient is older, sicker, or less able to follow a regimen exactly.” 

No study funding was reported. Dr. Visram reported consulting and honoraria relationships with Apotex, Janssen, and Sanofi. Other study authors reported multiple relationships with industry. Disclosures for Dr. Dunbar and Dr. Sekeres were unavailable. 

A version of this article appeared on Medscape.com.

SAN DIEGO — In the real world, outcomes for patients with multiple myeloma who received standard regimens were dramatically worse than those reported in clinical trials, a new study found. 

The analysis, which included nearly 4,000 patients with multiple myeloma, revealed that patients in a real-world setting demonstrated worse progression-free and overall survival on six of seven standard treatments compared with patients evaluated in randomized controlled trials.

Lead author Alissa Visram, MD, MPH, who spoke about the study at the annual meeting of the American Society of Hematology, said the findings will likely change the way she speaks to patients about their potential outcomes. 

“I’ll probably present both numbers [from real-life and clinical-trial data] and give them a sense of the best-case scenario,” Dr. Visram said during an ASH media briefing. But she said she will also caution her patients that the real-world numbers reflect how people on these drugs actually fare. 

The effectiveness of multiple myeloma drugs remains unclear outside the clinical trial setting, explained Dr. Visram, of the Division of Hematology at the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. Outcomes from randomized controlled trials form the basis of drug approvals but many patients in the real world do not meet the “stringent” trial inclusion criteria. 

Dr. Visram and colleagues launched the current study to better understand the potential differences between real-world and clinical trial outcomes. In the analysis, the researchers compared real-world outcomes among patients receiving seven standard multiple myeloma regimens covered by Ontario’s public health plan with patient outcomes reported in phase 3 randomized controlled trials. 

The retrospective study included 3951 patients with newly diagnosed and refractory multiple myeloma treated from 2007 to 2020 in Ontario. Regimens for newly diagnosed transplant ineligible patients included lenalidomide plus dexamethasone and triple therapy with bortezomib, lenalidomide, and dexamethasone. Regimens for patients with relapsed disease included pomalidomide plus dexamethasone or carfilzomib plus dexamethasone as well as triple combinations including carfilzomib, lenalidomide, and dexamethasone.

Overall, Dr. Visram and colleagues found that patients in the real-world setting demonstrated worse overall survival for six of the seven regimens evaluated (pooled hazard ratio [HR], 1.75; P = .010). 

The real-world patients also had worse progression-free survival for six of the seven regimens (pooled HR, 1.44; P = .034). 

For these regimens, progression-free survival was at least 3-18 months longer in the clinical trial cohort, while median overall survival was at least 19 months longer compared with real-world patients, Dr. Visram explained. 

The only regimen with comparable outcomes in the clinical trial and real-world settings was pomalidomide and dexamethasone, she said. One reason could be that patients receiving pomalidomide plus dexamethasone in the clinical trial setting had similar or more advanced disease than those in the real-world setting.

The study also found that adverse effects were similar between the clinical and real-world groups. 

The next step, Dr. Visram said, would be to explore what’s driving the differences in outcomes. 

Are patients in the real-world setting older or frailer? Do they have more advanced disease? Are providers using these regimens differently? 

Mikkael A. Sekeres, MD, MS, explained that the difference likely comes down to the health of the patient. 

Patients in these types of clinical trials “are just these pristine specimens of human beings except for the cancer that’s being treated,” Dr. Sekeres, of the Sylvester Comprehensive Cancer Center at the University of Miami, Florida, said in an earlier ASH press briefing.

Cynthia E. Dunbar, MD, noted that patients in clinical trials have other advantages as well.

“Patients who are able to enroll in clinical trials are more likely to be able to show up at the treatment center at the right time and for every dose, have transportation, and afford drugs to prevent side effects,” said Dr. Dunbar, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute and secretary of ASH. These patients also “might stay on the drug for longer, or they have nurses who are always encouraging them on how to make it through a toxicity.”

Dr. Dunbar said hematologists and patients should consider randomized controlled trials to be “the best possible outcome, and perhaps adjust their thinking if an individual patient is older, sicker, or less able to follow a regimen exactly.” 

No study funding was reported. Dr. Visram reported consulting and honoraria relationships with Apotex, Janssen, and Sanofi. Other study authors reported multiple relationships with industry. Disclosures for Dr. Dunbar and Dr. Sekeres were unavailable. 

A version of this article appeared on Medscape.com.

SAN DIEGO — In the real world, outcomes for patients with multiple myeloma who received standard regimens were dramatically worse than those reported in clinical trials, a new study found. 

The analysis, which included nearly 4,000 patients with multiple myeloma, revealed that patients in a real-world setting demonstrated worse progression-free and overall survival on six of seven standard treatments compared with patients evaluated in randomized controlled trials.

Lead author Alissa Visram, MD, MPH, who spoke about the study at the annual meeting of the American Society of Hematology, said the findings will likely change the way she speaks to patients about their potential outcomes. 

“I’ll probably present both numbers [from real-life and clinical-trial data] and give them a sense of the best-case scenario,” Dr. Visram said during an ASH media briefing. But she said she will also caution her patients that the real-world numbers reflect how people on these drugs actually fare. 

The effectiveness of multiple myeloma drugs remains unclear outside the clinical trial setting, explained Dr. Visram, of the Division of Hematology at the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. Outcomes from randomized controlled trials form the basis of drug approvals but many patients in the real world do not meet the “stringent” trial inclusion criteria. 

Dr. Visram and colleagues launched the current study to better understand the potential differences between real-world and clinical trial outcomes. In the analysis, the researchers compared real-world outcomes among patients receiving seven standard multiple myeloma regimens covered by Ontario’s public health plan with patient outcomes reported in phase 3 randomized controlled trials. 

The retrospective study included 3951 patients with newly diagnosed and refractory multiple myeloma treated from 2007 to 2020 in Ontario. Regimens for newly diagnosed transplant ineligible patients included lenalidomide plus dexamethasone and triple therapy with bortezomib, lenalidomide, and dexamethasone. Regimens for patients with relapsed disease included pomalidomide plus dexamethasone or carfilzomib plus dexamethasone as well as triple combinations including carfilzomib, lenalidomide, and dexamethasone.

Overall, Dr. Visram and colleagues found that patients in the real-world setting demonstrated worse overall survival for six of the seven regimens evaluated (pooled hazard ratio [HR], 1.75; P = .010). 

The real-world patients also had worse progression-free survival for six of the seven regimens (pooled HR, 1.44; P = .034). 

For these regimens, progression-free survival was at least 3-18 months longer in the clinical trial cohort, while median overall survival was at least 19 months longer compared with real-world patients, Dr. Visram explained. 

The only regimen with comparable outcomes in the clinical trial and real-world settings was pomalidomide and dexamethasone, she said. One reason could be that patients receiving pomalidomide plus dexamethasone in the clinical trial setting had similar or more advanced disease than those in the real-world setting.

The study also found that adverse effects were similar between the clinical and real-world groups. 

The next step, Dr. Visram said, would be to explore what’s driving the differences in outcomes. 

Are patients in the real-world setting older or frailer? Do they have more advanced disease? Are providers using these regimens differently? 

Mikkael A. Sekeres, MD, MS, explained that the difference likely comes down to the health of the patient. 

Patients in these types of clinical trials “are just these pristine specimens of human beings except for the cancer that’s being treated,” Dr. Sekeres, of the Sylvester Comprehensive Cancer Center at the University of Miami, Florida, said in an earlier ASH press briefing.

Cynthia E. Dunbar, MD, noted that patients in clinical trials have other advantages as well.

“Patients who are able to enroll in clinical trials are more likely to be able to show up at the treatment center at the right time and for every dose, have transportation, and afford drugs to prevent side effects,” said Dr. Dunbar, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute and secretary of ASH. These patients also “might stay on the drug for longer, or they have nurses who are always encouraging them on how to make it through a toxicity.”

Dr. Dunbar said hematologists and patients should consider randomized controlled trials to be “the best possible outcome, and perhaps adjust their thinking if an individual patient is older, sicker, or less able to follow a regimen exactly.” 

No study funding was reported. Dr. Visram reported consulting and honoraria relationships with Apotex, Janssen, and Sanofi. Other study authors reported multiple relationships with industry. Disclosures for Dr. Dunbar and Dr. Sekeres were unavailable. 

A version of this article appeared on Medscape.com.

SAN DIEGO — A polygenic score can link outcomes in Black pediatric patients with acute myeloid leukemia (AML) to genetic traits that arise more frequently in this population, new data reveal. 

The score, dubbed ACS10 and initially highlighted in a 2022 report, predicts how well patients will respond to cytarabine based on their genetic make-up, and has the potential to personalize treatment for Black pediatric patients, a group that often has worse outcomes than White patients.

In the current study, presented at the annual meeting of the American Society of Hematology (ASH) , Black patients with low ACS10 scores had significantly worse outcomes compared with those with high scores when initially treated with low-dose cytarabine, daunorubicin, and etoposide. 

The difference in outcomes disappeared, however, for patients who received high-dose cytarabine, daunorubicin, and etoposide or clofarabine and cytarabine. 

The genetic traits revealed by the test likely help explain why Black patients with AML typically fare worse on certain regimens, Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute, commented in an ASH press preview briefing.

This study also suggests that clinicians should perform testing for genetic variants and biomarkers that impact outcomes “instead of assuming that a certain dose should be given simply based on perceived or reported race or ethnicity,” said Dr. Dunbar, also secretary of ASH. 

The ACS10 test, derived from a combination of 10 single nucleotide polymorphisms, is not yet available, but one could be developed to help guide treatment decisions for clinicians, especially those in developing countries where AML treatment can be very expensive, said study lead author Jatinder Lamba, PhD, MSc, of the University of Florida College of Pharmacy, Gainesville, at an ASH press briefing on Thursday. 

Prior research shows that Black pediatric patients with AML often have worse outcomes than White patients. A recent study , for instance, found Black patients with AML, especially those aged 18 to 29 years, had a higher early death rate compared with White patients (16% vs 3%) and significantly lower 5-year overall survival rates (22% vs 51%). The authors of this study suggested that genetic differences between young Black and White patients could help explain the disparity. 

In the new analysis, Dr. Lamba and colleagues explored how outcomes by race and cytarabine pharmacogenomics varied in pediatric patients with AML. 

The study included 86 Black patients and 359 White patients with newly diagnosed AML treated on two multi-institutional clinical trials. The patients received one of three initial treatments that included cytarabine: high-dose or low-dose cytarabine, daunorubicin, and etoposide, or clofarabine and cytarabine. 

Most Black patients in the analysis (73%) had low ACS10 scores compared with 30% of White patients.

Unlike other recent reports, this study found that Black and White patients had similar complete remission rates following two courses of induction therapy (92.6% vs 95%) as well as similar rates of minimal residual disease negativity after one course (55.8% vs 55.4%). 

Event-free survival (EFS) and overall survival rates were also similar, with 5-year EFS estimates at 58.3% for Black patients and 58.2% for White patients and overall survival rates at 63.8% vs 69.4%, respectively (P = .24). 

However, when separating outcomes by ACS10 scores, Black patients with low scores had significantly worse EFS following low-dose cytarabine, daunorubicin, and etoposide compared with those with high ACS10 scores. And when these patients received high-dose cytarabine, daunorubicin, and etoposide or clofarabine and cytarabine induction therapy instead, the differences went away. 

Overall, Black patients demonstrated significantly better EFS following treatment with clofarabine and cytarabine compared with the low-dose cytarabine triple therapy (hazard ratio, 0.17; P = .01). After adjusting for cofounders, clofarabine and cytarabine induction was the best treatment for Black patients with low ACS10 scores (HR for EFS, 0.2).

“Our results suggest that pharmacogenomics differences between Black and White patients should be considered when tailoring induction regimens to improve outcomes of Black patients and bridge the racial disparity gap in AML treatment,” the researchers concluded.

In developing countries, especially in Africa, starting patients on high-dose cytarabine, daunorubicin, and etoposide can lead to better results “without increasing much of the economic burden” since this treatment is the cheapest, Dr. Lamba said. “At the same time, if the patients have high ACS10 score, you can reduce their economic burden by giving them standard dose” cytarabine, daunorubicin, and etoposide and achieve similar results.

No study funding was reported. Dr. Lamba reported no relevant financial relationships, and three other authors reported various disclosures. Disclosures for Dr. Dunbar were unavailable.. 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — A polygenic score can link outcomes in Black pediatric patients with acute myeloid leukemia (AML) to genetic traits that arise more frequently in this population, new data reveal. 

The score, dubbed ACS10 and initially highlighted in a 2022 report, predicts how well patients will respond to cytarabine based on their genetic make-up, and has the potential to personalize treatment for Black pediatric patients, a group that often has worse outcomes than White patients.

In the current study, presented at the annual meeting of the American Society of Hematology (ASH) , Black patients with low ACS10 scores had significantly worse outcomes compared with those with high scores when initially treated with low-dose cytarabine, daunorubicin, and etoposide. 

The difference in outcomes disappeared, however, for patients who received high-dose cytarabine, daunorubicin, and etoposide or clofarabine and cytarabine. 

The genetic traits revealed by the test likely help explain why Black patients with AML typically fare worse on certain regimens, Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute, commented in an ASH press preview briefing.

This study also suggests that clinicians should perform testing for genetic variants and biomarkers that impact outcomes “instead of assuming that a certain dose should be given simply based on perceived or reported race or ethnicity,” said Dr. Dunbar, also secretary of ASH. 

The ACS10 test, derived from a combination of 10 single nucleotide polymorphisms, is not yet available, but one could be developed to help guide treatment decisions for clinicians, especially those in developing countries where AML treatment can be very expensive, said study lead author Jatinder Lamba, PhD, MSc, of the University of Florida College of Pharmacy, Gainesville, at an ASH press briefing on Thursday. 

Prior research shows that Black pediatric patients with AML often have worse outcomes than White patients. A recent study , for instance, found Black patients with AML, especially those aged 18 to 29 years, had a higher early death rate compared with White patients (16% vs 3%) and significantly lower 5-year overall survival rates (22% vs 51%). The authors of this study suggested that genetic differences between young Black and White patients could help explain the disparity. 

In the new analysis, Dr. Lamba and colleagues explored how outcomes by race and cytarabine pharmacogenomics varied in pediatric patients with AML. 

The study included 86 Black patients and 359 White patients with newly diagnosed AML treated on two multi-institutional clinical trials. The patients received one of three initial treatments that included cytarabine: high-dose or low-dose cytarabine, daunorubicin, and etoposide, or clofarabine and cytarabine. 

Most Black patients in the analysis (73%) had low ACS10 scores compared with 30% of White patients.

Unlike other recent reports, this study found that Black and White patients had similar complete remission rates following two courses of induction therapy (92.6% vs 95%) as well as similar rates of minimal residual disease negativity after one course (55.8% vs 55.4%). 

Event-free survival (EFS) and overall survival rates were also similar, with 5-year EFS estimates at 58.3% for Black patients and 58.2% for White patients and overall survival rates at 63.8% vs 69.4%, respectively (P = .24). 

However, when separating outcomes by ACS10 scores, Black patients with low scores had significantly worse EFS following low-dose cytarabine, daunorubicin, and etoposide compared with those with high ACS10 scores. And when these patients received high-dose cytarabine, daunorubicin, and etoposide or clofarabine and cytarabine induction therapy instead, the differences went away. 

Overall, Black patients demonstrated significantly better EFS following treatment with clofarabine and cytarabine compared with the low-dose cytarabine triple therapy (hazard ratio, 0.17; P = .01). After adjusting for cofounders, clofarabine and cytarabine induction was the best treatment for Black patients with low ACS10 scores (HR for EFS, 0.2).

“Our results suggest that pharmacogenomics differences between Black and White patients should be considered when tailoring induction regimens to improve outcomes of Black patients and bridge the racial disparity gap in AML treatment,” the researchers concluded.

In developing countries, especially in Africa, starting patients on high-dose cytarabine, daunorubicin, and etoposide can lead to better results “without increasing much of the economic burden” since this treatment is the cheapest, Dr. Lamba said. “At the same time, if the patients have high ACS10 score, you can reduce their economic burden by giving them standard dose” cytarabine, daunorubicin, and etoposide and achieve similar results.

No study funding was reported. Dr. Lamba reported no relevant financial relationships, and three other authors reported various disclosures. Disclosures for Dr. Dunbar were unavailable.. 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — A polygenic score can link outcomes in Black pediatric patients with acute myeloid leukemia (AML) to genetic traits that arise more frequently in this population, new data reveal. 

The score, dubbed ACS10 and initially highlighted in a 2022 report, predicts how well patients will respond to cytarabine based on their genetic make-up, and has the potential to personalize treatment for Black pediatric patients, a group that often has worse outcomes than White patients.

In the current study, presented at the annual meeting of the American Society of Hematology (ASH) , Black patients with low ACS10 scores had significantly worse outcomes compared with those with high scores when initially treated with low-dose cytarabine, daunorubicin, and etoposide. 

The difference in outcomes disappeared, however, for patients who received high-dose cytarabine, daunorubicin, and etoposide or clofarabine and cytarabine. 

The genetic traits revealed by the test likely help explain why Black patients with AML typically fare worse on certain regimens, Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute, commented in an ASH press preview briefing.

This study also suggests that clinicians should perform testing for genetic variants and biomarkers that impact outcomes “instead of assuming that a certain dose should be given simply based on perceived or reported race or ethnicity,” said Dr. Dunbar, also secretary of ASH. 

The ACS10 test, derived from a combination of 10 single nucleotide polymorphisms, is not yet available, but one could be developed to help guide treatment decisions for clinicians, especially those in developing countries where AML treatment can be very expensive, said study lead author Jatinder Lamba, PhD, MSc, of the University of Florida College of Pharmacy, Gainesville, at an ASH press briefing on Thursday. 

Prior research shows that Black pediatric patients with AML often have worse outcomes than White patients. A recent study , for instance, found Black patients with AML, especially those aged 18 to 29 years, had a higher early death rate compared with White patients (16% vs 3%) and significantly lower 5-year overall survival rates (22% vs 51%). The authors of this study suggested that genetic differences between young Black and White patients could help explain the disparity. 

In the new analysis, Dr. Lamba and colleagues explored how outcomes by race and cytarabine pharmacogenomics varied in pediatric patients with AML. 

The study included 86 Black patients and 359 White patients with newly diagnosed AML treated on two multi-institutional clinical trials. The patients received one of three initial treatments that included cytarabine: high-dose or low-dose cytarabine, daunorubicin, and etoposide, or clofarabine and cytarabine. 

Most Black patients in the analysis (73%) had low ACS10 scores compared with 30% of White patients.

Unlike other recent reports, this study found that Black and White patients had similar complete remission rates following two courses of induction therapy (92.6% vs 95%) as well as similar rates of minimal residual disease negativity after one course (55.8% vs 55.4%). 

Event-free survival (EFS) and overall survival rates were also similar, with 5-year EFS estimates at 58.3% for Black patients and 58.2% for White patients and overall survival rates at 63.8% vs 69.4%, respectively (P = .24). 

However, when separating outcomes by ACS10 scores, Black patients with low scores had significantly worse EFS following low-dose cytarabine, daunorubicin, and etoposide compared with those with high ACS10 scores. And when these patients received high-dose cytarabine, daunorubicin, and etoposide or clofarabine and cytarabine induction therapy instead, the differences went away. 

Overall, Black patients demonstrated significantly better EFS following treatment with clofarabine and cytarabine compared with the low-dose cytarabine triple therapy (hazard ratio, 0.17; P = .01). After adjusting for cofounders, clofarabine and cytarabine induction was the best treatment for Black patients with low ACS10 scores (HR for EFS, 0.2).

“Our results suggest that pharmacogenomics differences between Black and White patients should be considered when tailoring induction regimens to improve outcomes of Black patients and bridge the racial disparity gap in AML treatment,” the researchers concluded.

In developing countries, especially in Africa, starting patients on high-dose cytarabine, daunorubicin, and etoposide can lead to better results “without increasing much of the economic burden” since this treatment is the cheapest, Dr. Lamba said. “At the same time, if the patients have high ACS10 score, you can reduce their economic burden by giving them standard dose” cytarabine, daunorubicin, and etoposide and achieve similar results.

No study funding was reported. Dr. Lamba reported no relevant financial relationships, and three other authors reported various disclosures. Disclosures for Dr. Dunbar were unavailable.. 
 

A version of this article appeared on Medscape.com.

Talk about bloodlines: In the Brodsky family, the field of hematology tied father to son. Now a grandson is heading into the “family business.” This extraordinary legacy ties the late Isadore Brodsky, a pioneering hematologist, to his son Robert A. Brodsky, current president of the American Society of Hematology (ASH), and grandson Max Brodsky, now a second-year hematology fellow.

In interviews, Robert and Max Brodsky spoke about the appeal of hematology and the threads that unite them with family members who came before. The elder Brodsky also talked about the work that’s made him the proudest during his year-long presidency at ASH.

Courtesy Dr. Robert A. Brodsky

Robert A. Brodsky is professor of medicine and director of hematology at Johns Hopkins University, Baltimore. He is stepping down as ASH president at its annual meeting in San Diego, December 9-12. Here are excerpts from our conversation:

Q: What drew your dad into medicine?

Dr. Robert A. Brodsky: He was going through his medical training at the University of Pennsylvania, then the Vietnam War came, and he served at the National Institutes of Health in what they referred to as the Yellow Berets. He got very interested in retroviruses and viruses that lead to cancer, which was a foreign idea at the time. This led him into hematology, stem cells, and myeloproliferative disorders.

He had a very successful career in hematology and just loved it. He performed the first bone marrow transplant in the tristate area of Pennsylvania, Delaware, and New Jersey.

Q: What did he like about hematology specifically?

Dr. Robert A. Brodsky: It’s a fascinating field, probably the most scientific area of medicine. It’s so easy to access blood and bone marrow. You can grow it, you can look at it, you can see it. It’s hard to do that with a lung, heart, kidney, or brain. Even back then, they could translate some of the science. What really drew him to hematology — and me, for that matter — was looking at a blood smear or bone marrow and being able to make a diagnosis. The other thing is the personal aspect. Hematologists tend to like the long-term relationships that they develop with their patients over the years.

Q: What were the biggest transformations in hematology during his career?

Dr. Robert A. Brodsky: Bone marrow transplant had the biggest impact, and it’s an area he really pioneered. He was very much involved in some of the early bone marrow transplants and was very close with Dr. George W. Santos, who was at Johns Hopkins and one of the big pioneers in that area as well. To be able to take marrow from related donors, get it to grow without the patient rejecting it, and cure a disease, was really huge. When he started doing this, patients had no other option. To see patients be cured was incredibly satisfying to him.

Q: How did you end up following your father into hematology?

Dr. Robert A. Brodsky: My brother Jeff, who’s a surgeon and older than me, knew he was going into medicine — probably about 3 hours after he was born. I came to it late. I was a political science major as an undergrad and really trying to figure out what I wanted to do. In my sophomore year, I decided I wanted to give this a shot. My dad worked very hard, long hours, but you could tell he loved what he did. And he was never absent, always involved in our lives and still made time for everyone. At some level, that must have had an influence on me.

Q: What has changed in hematology over your 30-plus years in medicine?

A: When I look back at when I was a fellow, it’s just mind-boggling how many lethal or life-threatening diseases are now pretty easy to treat. I studied disorders like aplastic anemia, which was very fatal. Without treatment, patients would die within a year. Now, over 95% are cured. Another classic examples is chronic myeloid leukemia disorder. Back when I was a fellow, the median survival for CML was maybe 4 to 6 years. Now, Kareem Abdul Jabbar has had this[for about 15 years]. Also a lot of hematologic malignancies are being cured with immunotherapy approaches. We’ve figured out the pathophysiology of a lot of diseases, and there are incredible genetic diagnostic assays.

Q: What was your father’s relationship with ASH?

Dr. Robert A. Brodsky: The first ASH meeting was 1958 in Atlantic City, New Jersey. There were 300 hematologists there, and my dad was one of them. We’re going to have over 30,000 people in San Diego, which is a record, and another 5,000 or 6,000 virtually.

Q: As ASH president, what are your biggest accomplishments when it comes to addressing the shortage of hematologists and other issues?

Dr. Robert A. Brodsky: ASH is investing $19 million to develop fellowships with a focus on hematology.* This is going to put lots of new hematologists into the workforce over the next 5 to 10 years. We’ve also been working on the Maintenance of Certification [MOC] process to make it less onerous on physicians. It’s really a bad process, and it’s not just ASH [that’s complaining], it’s all of medicine. We’re hearing this from GI, endocrine, renal and the general internists.

[In a September 2023 letter to the American Board of Internal Medicine’s president and chief officer, Dr. Brodsky wrote that “ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program.” ASH is calling for a new and reformed MOC program.]

Q: What convinced ASH to expand its journals by adding Blood Neoplasia and Blood Vessels, Thrombosis & Hemostasis?

Dr. Robert A. Brodsky: ASH has two flagship journals right now, Blood and Blood Advances, and they’re both very competitive, high-impact journals. It turns out there’s not enough room to publish all the new science, and they end up rejecting the majority of the submissions that come to them. We decided to keep these journals in the ASH family because there’s some fantastic clinical trials and science that would be going elsewhere.

Dr. Brodsky’s sons both have medical degrees: Brett Brodsky, DO, is a resident at Virginia Commonwealth University who plans to become a sports medicine specialist, and Max Brodsky, MD, is a second-year fellow in hematology at Johns Hopkins University.

In an interview, Max Brodsky, MD, talked about the roots of his family’s dedication to caring for others.

Q: What drew you to hematology?

Dr. Max Brodsky: I’ve watched both my dad and my grandfather be leaders in the field as both physicians and scientists, and that was very inspirational for me to see. And I went to a medical school [Drexel University College of Medicine] that my dad went to and where my grandfather was on faculty. That was like walking in their footsteps in a major way.

Q: What do you hope to focus on as a hematologist?

Dr. Max Brodsky: I’m still working through that, but I am really interested in thrombotic thrombocytopenic purpura. Patients used to not be able to survive their initial episodes, but now we have good treatments and are able to follow them as outpatients. With this whole cohort of patients that are surviving, we’re seeing that they have more health problems — more heart disease, more strokes and kidney disease. There’s a whole growing field exploring how to treat these patients for their lifespan.

Q: How do you deal with the reality that more of your patients will die than in some other medical fields?

Dr. Max Brodsky: It is challenging, but I also see those moments as opportunities to support patients and families. I’m good at connecting to patients and families who are in scary situations. I’ve always had that skill of putting people at ease, making people feel calm, knowing that they can trust me, and I have their best interests in mind.

Q: Why do you think your family is so committed to medicine?

Dr. Max Brodsky: We’re Jewish, and looking to help the world is one of the main core values of Judaism. The Torah expects us to make this world better.  Actually, my great-grandfather Max, whom I’m named after, used to dig tunnels to help people escape Ukraine and get to freedom. He was always looking to help others as well. My great-grandmother was shot crossing the border escaping from Ukraine, and he carried her the whole way to the boat. They lived in very poor West Philadelphia and poured everything into my grandfather. He became a great doctor, and his sons and his grandchildren are in medicine today.

*Correction, 12/11: A previous version of this story misstated the amount of ASH’s $19 million investment in developing fellowships with a focus on hematology.

Talk about bloodlines: In the Brodsky family, the field of hematology tied father to son. Now a grandson is heading into the “family business.” This extraordinary legacy ties the late Isadore Brodsky, a pioneering hematologist, to his son Robert A. Brodsky, current president of the American Society of Hematology (ASH), and grandson Max Brodsky, now a second-year hematology fellow.

In interviews, Robert and Max Brodsky spoke about the appeal of hematology and the threads that unite them with family members who came before. The elder Brodsky also talked about the work that’s made him the proudest during his year-long presidency at ASH.

Courtesy Dr. Robert A. Brodsky

Robert A. Brodsky is professor of medicine and director of hematology at Johns Hopkins University, Baltimore. He is stepping down as ASH president at its annual meeting in San Diego, December 9-12. Here are excerpts from our conversation:

Q: What drew your dad into medicine?

Dr. Robert A. Brodsky: He was going through his medical training at the University of Pennsylvania, then the Vietnam War came, and he served at the National Institutes of Health in what they referred to as the Yellow Berets. He got very interested in retroviruses and viruses that lead to cancer, which was a foreign idea at the time. This led him into hematology, stem cells, and myeloproliferative disorders.

He had a very successful career in hematology and just loved it. He performed the first bone marrow transplant in the tristate area of Pennsylvania, Delaware, and New Jersey.

Q: What did he like about hematology specifically?

Dr. Robert A. Brodsky: It’s a fascinating field, probably the most scientific area of medicine. It’s so easy to access blood and bone marrow. You can grow it, you can look at it, you can see it. It’s hard to do that with a lung, heart, kidney, or brain. Even back then, they could translate some of the science. What really drew him to hematology — and me, for that matter — was looking at a blood smear or bone marrow and being able to make a diagnosis. The other thing is the personal aspect. Hematologists tend to like the long-term relationships that they develop with their patients over the years.

Q: What were the biggest transformations in hematology during his career?

Dr. Robert A. Brodsky: Bone marrow transplant had the biggest impact, and it’s an area he really pioneered. He was very much involved in some of the early bone marrow transplants and was very close with Dr. George W. Santos, who was at Johns Hopkins and one of the big pioneers in that area as well. To be able to take marrow from related donors, get it to grow without the patient rejecting it, and cure a disease, was really huge. When he started doing this, patients had no other option. To see patients be cured was incredibly satisfying to him.

Q: How did you end up following your father into hematology?

Dr. Robert A. Brodsky: My brother Jeff, who’s a surgeon and older than me, knew he was going into medicine — probably about 3 hours after he was born. I came to it late. I was a political science major as an undergrad and really trying to figure out what I wanted to do. In my sophomore year, I decided I wanted to give this a shot. My dad worked very hard, long hours, but you could tell he loved what he did. And he was never absent, always involved in our lives and still made time for everyone. At some level, that must have had an influence on me.

Q: What has changed in hematology over your 30-plus years in medicine?

A: When I look back at when I was a fellow, it’s just mind-boggling how many lethal or life-threatening diseases are now pretty easy to treat. I studied disorders like aplastic anemia, which was very fatal. Without treatment, patients would die within a year. Now, over 95% are cured. Another classic examples is chronic myeloid leukemia disorder. Back when I was a fellow, the median survival for CML was maybe 4 to 6 years. Now, Kareem Abdul Jabbar has had this[for about 15 years]. Also a lot of hematologic malignancies are being cured with immunotherapy approaches. We’ve figured out the pathophysiology of a lot of diseases, and there are incredible genetic diagnostic assays.

Q: What was your father’s relationship with ASH?

Dr. Robert A. Brodsky: The first ASH meeting was 1958 in Atlantic City, New Jersey. There were 300 hematologists there, and my dad was one of them. We’re going to have over 30,000 people in San Diego, which is a record, and another 5,000 or 6,000 virtually.

Q: As ASH president, what are your biggest accomplishments when it comes to addressing the shortage of hematologists and other issues?

Dr. Robert A. Brodsky: ASH is investing $19 million to develop fellowships with a focus on hematology.* This is going to put lots of new hematologists into the workforce over the next 5 to 10 years. We’ve also been working on the Maintenance of Certification [MOC] process to make it less onerous on physicians. It’s really a bad process, and it’s not just ASH [that’s complaining], it’s all of medicine. We’re hearing this from GI, endocrine, renal and the general internists.

[In a September 2023 letter to the American Board of Internal Medicine’s president and chief officer, Dr. Brodsky wrote that “ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program.” ASH is calling for a new and reformed MOC program.]

Q: What convinced ASH to expand its journals by adding Blood Neoplasia and Blood Vessels, Thrombosis & Hemostasis?

Dr. Robert A. Brodsky: ASH has two flagship journals right now, Blood and Blood Advances, and they’re both very competitive, high-impact journals. It turns out there’s not enough room to publish all the new science, and they end up rejecting the majority of the submissions that come to them. We decided to keep these journals in the ASH family because there’s some fantastic clinical trials and science that would be going elsewhere.

Dr. Brodsky’s sons both have medical degrees: Brett Brodsky, DO, is a resident at Virginia Commonwealth University who plans to become a sports medicine specialist, and Max Brodsky, MD, is a second-year fellow in hematology at Johns Hopkins University.

In an interview, Max Brodsky, MD, talked about the roots of his family’s dedication to caring for others.

Q: What drew you to hematology?

Dr. Max Brodsky: I’ve watched both my dad and my grandfather be leaders in the field as both physicians and scientists, and that was very inspirational for me to see. And I went to a medical school [Drexel University College of Medicine] that my dad went to and where my grandfather was on faculty. That was like walking in their footsteps in a major way.

Q: What do you hope to focus on as a hematologist?

Dr. Max Brodsky: I’m still working through that, but I am really interested in thrombotic thrombocytopenic purpura. Patients used to not be able to survive their initial episodes, but now we have good treatments and are able to follow them as outpatients. With this whole cohort of patients that are surviving, we’re seeing that they have more health problems — more heart disease, more strokes and kidney disease. There’s a whole growing field exploring how to treat these patients for their lifespan.

Q: How do you deal with the reality that more of your patients will die than in some other medical fields?

Dr. Max Brodsky: It is challenging, but I also see those moments as opportunities to support patients and families. I’m good at connecting to patients and families who are in scary situations. I’ve always had that skill of putting people at ease, making people feel calm, knowing that they can trust me, and I have their best interests in mind.

Q: Why do you think your family is so committed to medicine?

Dr. Max Brodsky: We’re Jewish, and looking to help the world is one of the main core values of Judaism. The Torah expects us to make this world better.  Actually, my great-grandfather Max, whom I’m named after, used to dig tunnels to help people escape Ukraine and get to freedom. He was always looking to help others as well. My great-grandmother was shot crossing the border escaping from Ukraine, and he carried her the whole way to the boat. They lived in very poor West Philadelphia and poured everything into my grandfather. He became a great doctor, and his sons and his grandchildren are in medicine today.

*Correction, 12/11: A previous version of this story misstated the amount of ASH’s $19 million investment in developing fellowships with a focus on hematology.

Talk about bloodlines: In the Brodsky family, the field of hematology tied father to son. Now a grandson is heading into the “family business.” This extraordinary legacy ties the late Isadore Brodsky, a pioneering hematologist, to his son Robert A. Brodsky, current president of the American Society of Hematology (ASH), and grandson Max Brodsky, now a second-year hematology fellow.

In interviews, Robert and Max Brodsky spoke about the appeal of hematology and the threads that unite them with family members who came before. The elder Brodsky also talked about the work that’s made him the proudest during his year-long presidency at ASH.

Courtesy Dr. Robert A. Brodsky

Robert A. Brodsky is professor of medicine and director of hematology at Johns Hopkins University, Baltimore. He is stepping down as ASH president at its annual meeting in San Diego, December 9-12. Here are excerpts from our conversation:

Q: What drew your dad into medicine?

Dr. Robert A. Brodsky: He was going through his medical training at the University of Pennsylvania, then the Vietnam War came, and he served at the National Institutes of Health in what they referred to as the Yellow Berets. He got very interested in retroviruses and viruses that lead to cancer, which was a foreign idea at the time. This led him into hematology, stem cells, and myeloproliferative disorders.

He had a very successful career in hematology and just loved it. He performed the first bone marrow transplant in the tristate area of Pennsylvania, Delaware, and New Jersey.

Q: What did he like about hematology specifically?

Dr. Robert A. Brodsky: It’s a fascinating field, probably the most scientific area of medicine. It’s so easy to access blood and bone marrow. You can grow it, you can look at it, you can see it. It’s hard to do that with a lung, heart, kidney, or brain. Even back then, they could translate some of the science. What really drew him to hematology — and me, for that matter — was looking at a blood smear or bone marrow and being able to make a diagnosis. The other thing is the personal aspect. Hematologists tend to like the long-term relationships that they develop with their patients over the years.

Q: What were the biggest transformations in hematology during his career?

Dr. Robert A. Brodsky: Bone marrow transplant had the biggest impact, and it’s an area he really pioneered. He was very much involved in some of the early bone marrow transplants and was very close with Dr. George W. Santos, who was at Johns Hopkins and one of the big pioneers in that area as well. To be able to take marrow from related donors, get it to grow without the patient rejecting it, and cure a disease, was really huge. When he started doing this, patients had no other option. To see patients be cured was incredibly satisfying to him.

Q: How did you end up following your father into hematology?

Dr. Robert A. Brodsky: My brother Jeff, who’s a surgeon and older than me, knew he was going into medicine — probably about 3 hours after he was born. I came to it late. I was a political science major as an undergrad and really trying to figure out what I wanted to do. In my sophomore year, I decided I wanted to give this a shot. My dad worked very hard, long hours, but you could tell he loved what he did. And he was never absent, always involved in our lives and still made time for everyone. At some level, that must have had an influence on me.

Q: What has changed in hematology over your 30-plus years in medicine?

A: When I look back at when I was a fellow, it’s just mind-boggling how many lethal or life-threatening diseases are now pretty easy to treat. I studied disorders like aplastic anemia, which was very fatal. Without treatment, patients would die within a year. Now, over 95% are cured. Another classic examples is chronic myeloid leukemia disorder. Back when I was a fellow, the median survival for CML was maybe 4 to 6 years. Now, Kareem Abdul Jabbar has had this[for about 15 years]. Also a lot of hematologic malignancies are being cured with immunotherapy approaches. We’ve figured out the pathophysiology of a lot of diseases, and there are incredible genetic diagnostic assays.

Q: What was your father’s relationship with ASH?

Dr. Robert A. Brodsky: The first ASH meeting was 1958 in Atlantic City, New Jersey. There were 300 hematologists there, and my dad was one of them. We’re going to have over 30,000 people in San Diego, which is a record, and another 5,000 or 6,000 virtually.

Q: As ASH president, what are your biggest accomplishments when it comes to addressing the shortage of hematologists and other issues?

Dr. Robert A. Brodsky: ASH is investing $19 million to develop fellowships with a focus on hematology.* This is going to put lots of new hematologists into the workforce over the next 5 to 10 years. We’ve also been working on the Maintenance of Certification [MOC] process to make it less onerous on physicians. It’s really a bad process, and it’s not just ASH [that’s complaining], it’s all of medicine. We’re hearing this from GI, endocrine, renal and the general internists.

[In a September 2023 letter to the American Board of Internal Medicine’s president and chief officer, Dr. Brodsky wrote that “ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program.” ASH is calling for a new and reformed MOC program.]

Q: What convinced ASH to expand its journals by adding Blood Neoplasia and Blood Vessels, Thrombosis & Hemostasis?

Dr. Robert A. Brodsky: ASH has two flagship journals right now, Blood and Blood Advances, and they’re both very competitive, high-impact journals. It turns out there’s not enough room to publish all the new science, and they end up rejecting the majority of the submissions that come to them. We decided to keep these journals in the ASH family because there’s some fantastic clinical trials and science that would be going elsewhere.

Dr. Brodsky’s sons both have medical degrees: Brett Brodsky, DO, is a resident at Virginia Commonwealth University who plans to become a sports medicine specialist, and Max Brodsky, MD, is a second-year fellow in hematology at Johns Hopkins University.

In an interview, Max Brodsky, MD, talked about the roots of his family’s dedication to caring for others.

Q: What drew you to hematology?

Dr. Max Brodsky: I’ve watched both my dad and my grandfather be leaders in the field as both physicians and scientists, and that was very inspirational for me to see. And I went to a medical school [Drexel University College of Medicine] that my dad went to and where my grandfather was on faculty. That was like walking in their footsteps in a major way.

Q: What do you hope to focus on as a hematologist?

Dr. Max Brodsky: I’m still working through that, but I am really interested in thrombotic thrombocytopenic purpura. Patients used to not be able to survive their initial episodes, but now we have good treatments and are able to follow them as outpatients. With this whole cohort of patients that are surviving, we’re seeing that they have more health problems — more heart disease, more strokes and kidney disease. There’s a whole growing field exploring how to treat these patients for their lifespan.

Q: How do you deal with the reality that more of your patients will die than in some other medical fields?

Dr. Max Brodsky: It is challenging, but I also see those moments as opportunities to support patients and families. I’m good at connecting to patients and families who are in scary situations. I’ve always had that skill of putting people at ease, making people feel calm, knowing that they can trust me, and I have their best interests in mind.

Q: Why do you think your family is so committed to medicine?

Dr. Max Brodsky: We’re Jewish, and looking to help the world is one of the main core values of Judaism. The Torah expects us to make this world better.  Actually, my great-grandfather Max, whom I’m named after, used to dig tunnels to help people escape Ukraine and get to freedom. He was always looking to help others as well. My great-grandmother was shot crossing the border escaping from Ukraine, and he carried her the whole way to the boat. They lived in very poor West Philadelphia and poured everything into my grandfather. He became a great doctor, and his sons and his grandchildren are in medicine today.

*Correction, 12/11: A previous version of this story misstated the amount of ASH’s $19 million investment in developing fellowships with a focus on hematology.

Health equity, sickle cell disease (SCD), and the thoughtful use of artificial intelligence (AI) and social media are among the key themes to be presented at the Dec. 9-12 annual meeting of the American Society of Hematology (ASH) in San Diego, association leaders told reporters in a media preview session.

Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute and secretary of ASH, added that insight into actual patient experiences also will be a major theme at ASH 2023.

“There is a huge growth in research on outcomes and focusing on using real-world data and how important that is,” Dr. Dunbar said. “Academic research and hematology is really focusing on patient-reported outcomes and how care is delivered in a real-world setting – actually looking at what matters to patients. Are they alive in a certain number of years? And how are they feeling?”

As an example, Dr. Dunbar pointed to an abstract that examined clinical databases in Canada and found that real-world outcomes in multiple myeloma treatments were much worse than those in the original clinical trials for the therapies. Patients reached relapse 44% faster and their overall survival was 75% worse.

In the media briefing, ASH chair of communications Mikkael A. Sekeres, MD, MS, of the Sylvester Comprehensive Cancer Center at the University of Miami, noted that patients in these types of clinical trials “are just these pristine specimens of human beings except for the cancer that’s being treated.”

Dr. Dunbar agreed, noting that “patients who are able to enroll in clinical trials are more likely to be able to show up at the treatment center at the right time and for every dose, have transportation, and afford drugs to prevent side effects. They might stay on the drug for longer, or they have nurses who are always encouraging them of how to make it through a toxicity.”

Hematologists and patients should consider randomized controlled trials to be “the best possible outcome, and perhaps adjust their thinking if an individual patient is older, sicker, or less able to follow a regimen exactly,” she said.

Another highlighted study linked worse outcomes in African-Americans with pediatric acute myeloid leukemia to genetic traits that are more common in that population. The traits “likely explain at least in part the worst outcomes in Black patients in prior studies and on some regimens,” Dr. Dunbar said.

She added that the findings emphasize how testing for genetic variants and biomarkers that impact outcomes should be performed “instead of assuming that a certain dose should be given simply based on perceived or reported race or ethnicity.”

ASH President Robert A. Brodsky, MD, of Johns Hopkins University School of Medicine, Baltimore, highlighted an abstract that reported on the use of AI as a clinical decision support tool to differentiate two easily confused conditions — prefibrotic primary myelofibrosis and essential thrombocythemia.

AI “is a tool that’s going to help pathologists make more accurate and faster diagnoses,” he said. He also spotlighted an abstract about the use of “social media listening” to understand the experiences of patients with SCD and their caregivers. “There can be a lot of misuse and waste of time with social media, but they used this in a way to try and gain insight as to what’s really important to the patients and the caregiver.”

Also, in regard to SCD, Dr. Dunbar pointed to a study that reports on outcomes in patients who received lovotibeglogene autotemcel (lovo-cel) gene therapy for up to 60 months. Both this treatment and a CRISPR-based therapy called exa-cel  “appear to result in comparable very impressive efficacy in terms of pain crises and organ dysfunction,” she said. “The hurdle is going to be figuring out how to deliver what will be very expensive and complicated therapies — but likely curative — therapies to patients.”

Another study to be presented at ASH — coauthored by Dr. Brodsky — shows promising results from reduced-intensity haploidentical bone marrow transplantation in adults with severe SCD. Results were similar to those seen with bone marrow from matched siblings, Dr. Sekeres said.

He added that more clarity is needed about new treatment options for SCD, perhaps through a “randomized trial where patients upfront get a haploidentical bone marrow transplant or fully matched bone marrow transplant. Then other patients are randomized to some of these other, newer technology therapies, and we follow them over time. We’re looking not only for overall survival but complications of the therapy itself and how many patients relapse from the treatment.”

Health equity, sickle cell disease (SCD), and the thoughtful use of artificial intelligence (AI) and social media are among the key themes to be presented at the Dec. 9-12 annual meeting of the American Society of Hematology (ASH) in San Diego, association leaders told reporters in a media preview session.

Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute and secretary of ASH, added that insight into actual patient experiences also will be a major theme at ASH 2023.

“There is a huge growth in research on outcomes and focusing on using real-world data and how important that is,” Dr. Dunbar said. “Academic research and hematology is really focusing on patient-reported outcomes and how care is delivered in a real-world setting – actually looking at what matters to patients. Are they alive in a certain number of years? And how are they feeling?”

As an example, Dr. Dunbar pointed to an abstract that examined clinical databases in Canada and found that real-world outcomes in multiple myeloma treatments were much worse than those in the original clinical trials for the therapies. Patients reached relapse 44% faster and their overall survival was 75% worse.

In the media briefing, ASH chair of communications Mikkael A. Sekeres, MD, MS, of the Sylvester Comprehensive Cancer Center at the University of Miami, noted that patients in these types of clinical trials “are just these pristine specimens of human beings except for the cancer that’s being treated.”

Dr. Dunbar agreed, noting that “patients who are able to enroll in clinical trials are more likely to be able to show up at the treatment center at the right time and for every dose, have transportation, and afford drugs to prevent side effects. They might stay on the drug for longer, or they have nurses who are always encouraging them of how to make it through a toxicity.”

Hematologists and patients should consider randomized controlled trials to be “the best possible outcome, and perhaps adjust their thinking if an individual patient is older, sicker, or less able to follow a regimen exactly,” she said.

Another highlighted study linked worse outcomes in African-Americans with pediatric acute myeloid leukemia to genetic traits that are more common in that population. The traits “likely explain at least in part the worst outcomes in Black patients in prior studies and on some regimens,” Dr. Dunbar said.

She added that the findings emphasize how testing for genetic variants and biomarkers that impact outcomes should be performed “instead of assuming that a certain dose should be given simply based on perceived or reported race or ethnicity.”

ASH President Robert A. Brodsky, MD, of Johns Hopkins University School of Medicine, Baltimore, highlighted an abstract that reported on the use of AI as a clinical decision support tool to differentiate two easily confused conditions — prefibrotic primary myelofibrosis and essential thrombocythemia.

AI “is a tool that’s going to help pathologists make more accurate and faster diagnoses,” he said. He also spotlighted an abstract about the use of “social media listening” to understand the experiences of patients with SCD and their caregivers. “There can be a lot of misuse and waste of time with social media, but they used this in a way to try and gain insight as to what’s really important to the patients and the caregiver.”

Also, in regard to SCD, Dr. Dunbar pointed to a study that reports on outcomes in patients who received lovotibeglogene autotemcel (lovo-cel) gene therapy for up to 60 months. Both this treatment and a CRISPR-based therapy called exa-cel  “appear to result in comparable very impressive efficacy in terms of pain crises and organ dysfunction,” she said. “The hurdle is going to be figuring out how to deliver what will be very expensive and complicated therapies — but likely curative — therapies to patients.”

Another study to be presented at ASH — coauthored by Dr. Brodsky — shows promising results from reduced-intensity haploidentical bone marrow transplantation in adults with severe SCD. Results were similar to those seen with bone marrow from matched siblings, Dr. Sekeres said.

He added that more clarity is needed about new treatment options for SCD, perhaps through a “randomized trial where patients upfront get a haploidentical bone marrow transplant or fully matched bone marrow transplant. Then other patients are randomized to some of these other, newer technology therapies, and we follow them over time. We’re looking not only for overall survival but complications of the therapy itself and how many patients relapse from the treatment.”

Health equity, sickle cell disease (SCD), and the thoughtful use of artificial intelligence (AI) and social media are among the key themes to be presented at the Dec. 9-12 annual meeting of the American Society of Hematology (ASH) in San Diego, association leaders told reporters in a media preview session.

Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute and secretary of ASH, added that insight into actual patient experiences also will be a major theme at ASH 2023.

“There is a huge growth in research on outcomes and focusing on using real-world data and how important that is,” Dr. Dunbar said. “Academic research and hematology is really focusing on patient-reported outcomes and how care is delivered in a real-world setting – actually looking at what matters to patients. Are they alive in a certain number of years? And how are they feeling?”

As an example, Dr. Dunbar pointed to an abstract that examined clinical databases in Canada and found that real-world outcomes in multiple myeloma treatments were much worse than those in the original clinical trials for the therapies. Patients reached relapse 44% faster and their overall survival was 75% worse.

In the media briefing, ASH chair of communications Mikkael A. Sekeres, MD, MS, of the Sylvester Comprehensive Cancer Center at the University of Miami, noted that patients in these types of clinical trials “are just these pristine specimens of human beings except for the cancer that’s being treated.”

Dr. Dunbar agreed, noting that “patients who are able to enroll in clinical trials are more likely to be able to show up at the treatment center at the right time and for every dose, have transportation, and afford drugs to prevent side effects. They might stay on the drug for longer, or they have nurses who are always encouraging them of how to make it through a toxicity.”

Hematologists and patients should consider randomized controlled trials to be “the best possible outcome, and perhaps adjust their thinking if an individual patient is older, sicker, or less able to follow a regimen exactly,” she said.

Another highlighted study linked worse outcomes in African-Americans with pediatric acute myeloid leukemia to genetic traits that are more common in that population. The traits “likely explain at least in part the worst outcomes in Black patients in prior studies and on some regimens,” Dr. Dunbar said.

She added that the findings emphasize how testing for genetic variants and biomarkers that impact outcomes should be performed “instead of assuming that a certain dose should be given simply based on perceived or reported race or ethnicity.”

ASH President Robert A. Brodsky, MD, of Johns Hopkins University School of Medicine, Baltimore, highlighted an abstract that reported on the use of AI as a clinical decision support tool to differentiate two easily confused conditions — prefibrotic primary myelofibrosis and essential thrombocythemia.

AI “is a tool that’s going to help pathologists make more accurate and faster diagnoses,” he said. He also spotlighted an abstract about the use of “social media listening” to understand the experiences of patients with SCD and their caregivers. “There can be a lot of misuse and waste of time with social media, but they used this in a way to try and gain insight as to what’s really important to the patients and the caregiver.”

Also, in regard to SCD, Dr. Dunbar pointed to a study that reports on outcomes in patients who received lovotibeglogene autotemcel (lovo-cel) gene therapy for up to 60 months. Both this treatment and a CRISPR-based therapy called exa-cel  “appear to result in comparable very impressive efficacy in terms of pain crises and organ dysfunction,” she said. “The hurdle is going to be figuring out how to deliver what will be very expensive and complicated therapies — but likely curative — therapies to patients.”

Another study to be presented at ASH — coauthored by Dr. Brodsky — shows promising results from reduced-intensity haploidentical bone marrow transplantation in adults with severe SCD. Results were similar to those seen with bone marrow from matched siblings, Dr. Sekeres said.

He added that more clarity is needed about new treatment options for SCD, perhaps through a “randomized trial where patients upfront get a haploidentical bone marrow transplant or fully matched bone marrow transplant. Then other patients are randomized to some of these other, newer technology therapies, and we follow them over time. We’re looking not only for overall survival but complications of the therapy itself and how many patients relapse from the treatment.”