Conference Coverage

ORLANDO — It’s important for pediatricians not only to understand the causes and effects of climate change but also to know how to discuss this issue with families and make risk-based adjustments to their clinical practice based on the individual health and circumstances of each patient. That’s one of the key messages delivered at the annual meeting of the American Academy of Pediatrics (AAP) by Elizabeth C. Matsui, MD, MHS, professor of population health and pediatrics and director of the Center for Health and Environment Education and Research at the University of Texas at Austin Dell Medical School. 

“Even though climate change has been here and has been affecting health already for a while, it’s just really impossible to ignore right now,” she told attendees in a session focused on climate change impacts on allergies and asthma. “The challenge is connecting the dots between something that is much larger, or feels much larger, than the patient and the family that’s in front of you.” 

The reality, however, is that climate change is now impacting patients’ health on an individual level, and pediatricians have a responsibility to understand how that’s happening and to help their families prepare for it. 

“From the perspective of someone who went into medicine to practice and take care of the individual patient, I think it has been more difficult to connect those dots, and for the people in this room, it’s our job to connect those dots,” Matsui said. She also acknowledged that many of the solutions are frustratingly limited to the policy level and challenging to implement, “but it doesn’t mean that we can’t make a difference for the patients who are in front of us.” 

Charles Moon, MD, a pediatrician and Pediatric Environmental Health Fellow at the Children’s Environmental Health Center, Icahn School of Medicine at Mount Sinai, New York City, found the talk particularly helpful in providing information about both the broader issue and what it means on a local practice level. 

“The biggest takeaway is that more people and more pediatricians are tuning in to this issue and realizing the dangers,” Moon said. “It’s clear that a larger community is forming around this, and I think we are at the cusp where more and more people will be coming in. We are really focusing on taking all the data and trying to figure out solutions. I think the solutions orientation is the most important part.” 
 

Understanding the Big Picture

Matsui opened with a general discussion of the human causes of climate change and the effects on a global scale presently and in the future. For example, over the past 800,000 years, carbon dioxide levels have never been above 300 ppm, but they surpassed that threshold in 1911 and have reached 420 ppm today. The trapping of heat in Earth’s atmosphere caused by the increase in carbon dioxide and other greenhouse gases is leading to multiple phenomena that impact health, such as longer growing seasons; increased droughts, heat waves, and wildfire seasons; and higher temperatures. These changes, in turn, affect allergens and asthma.

Children are particularly vulnerable to climate change impacts because they have a higher risk for developing asthma, allergic disease, and infections, Matsui said. Childhood is a critical period for lung and immune development, and the Environmental Protection Agency’s 2023 Climate Change and Children’s Health and Well-Being report projects that an increase of 2° C in global warming will result in an additional 34,500 pediatric asthma cases and 228,000 allergic rhinitis cases per year, driven largely by predicted increases in ozone and 2.5-µm particulate matter. The report also forecasts an increase in 6240 asthma emergency department visits and 332 additional respiratory hospitalizations per year. 

“We know that these associations that we see between climate change exposures and poor respiratory health outcomes in kids are biologically plausible,” Matsui said. “They’re not just correlation without causation. A lot of the mechanisms for how air pollution, allergies, and other factors directly affect the lungs of the airway epithelium have been worked out.” 
 

An Increase in Allergens and Viral Infections

Pediatricians should prepare for anticipated growth in allergens and viral infections. The longer growing seasons mean that pollen seasons will also lengthen. Meanwhile, higher concentrations of carbon dioxide cause individual plants to produce more pollen. 

“As the winters get warmer, mice that might not be able to survive during the winter are surviving, and mice reproduce at a very rapid rate,” she said. “The increase in moisture means that dust mites, which absorb their water — they drink by absorbing humidity that’s in the air — will be present in higher concentrations, and their range will expand.”

Fungal and mold exposures are also increasing, not just outdoors but also indoors, “and there are all sorts of allergic and respiratory health consequences of fungal exposure,” Matsui said. As hurricanes and flooding increase, storm damage can also make indoor environments more conducive to fungal and mold growth. 

Extreme weather from climate change also affects infrastructure. “When there’s healthcare infrastructure disruption and other infrastructure disruption, it adds to the challenge,” she said. “It compounds all the other threat to health from climate change, so this overall problem of climate change and health is multidimensional and very complicated.”

Then there’s the impact of climate change on respiratory viruses, which are a major driver of asthma exacerbations, Matsui said. The greater variability in daytime temperatures affects environmental reservoirs, transmission patterns, geographical ranges, and seasonality of various respiratory pathogens. The prevalence of respiratory syncytial virus infections, for example, increases during humid periods. 

“This is coupled with the fact that the projected increases in air pollution increase susceptibility to respiratory virus infections,” Matsui said. “In fact, climate change and air pollution are inextricably linked.” 
 

Climate Change and Air Pollution

Climate disruption creates extreme weather patterns that then lead to worsening air quality due to high temperatures; heavier precipitation; and more forest fires, droughts, dust storms, thunderstorms, hurricanes, stagnation events, and other extreme weather. Matsui shared a map showing the substantial increase in days with stagnant air since 1973. During stagnation events, air pollution builds up in the atmosphere because of a stable air mass that remains over a region for several days, with low-level winds and no precipitation. 

The pollutants can then contribute to rising temperatures. Black carbon particulate matter released from the burning of forests and other biomass absorbs more solar radiation, further contributing to temperature increases. Data from the National Bureau of Economic Research has shown that the US made big strides in reducing air pollution from 2009 through 2016, but it began to reverse in 2016 as severe weather events picked up. 

Pediatricians need to be cognizant of the synergistic effect of these different impacts as well. “We oftentimes talk about these problems in a silo, so we may talk about air pollution and health effects, or allergens and health effects, or heat and health effects, but all of these interact with each other and further compound the health effects,” compared to just one of them in isolation, Matsui said.

For example, air pollution increases sensitivity to allergen exposure and increases reaction severity, which disrupts the immune tolerance to allergens. “Heat and air pollution also interact, and the combination of the two is more deadly than either one alone,” she said. 

Air pollution from wildfire smoke is also more toxic to the lungs than air pollution from other sources, so if there’s wildfire-based air pollution, the impact on respiratory hospitalizations is significantly greater. Even in places that would not otherwise be at risk for wildfires, the threat remains of air pollution from more distant fires, as New York City experienced from Canadian wildfires last year. 

“This is a problem that is not just isolated to the parts of the world where the wildfires are located,” Matsui said.

Moon, who practices in New York City, said he really appreciated Matsui’s perspectives and nuanced advice as a subspecialist “because it’s obvious that the way we deliver healthcare is going to have to change based on climate change.” He hopes to see more subspecialists from other pediatric areas getting involved in looking at climate impacts and providing nuanced advice about changing clinical care similar to the examples Matsui provided. 

Air pollution can also be deadly, as a landmark case in the United Kingdom revealed a few years ago when the court ruled that a child’s death from an asthma attack was directly due to air pollution. In addition to causing worse asthma symptoms and exacerbations, air pollution also adds to the risk of developing asthma and impedes lung growth, all of which disproportionately affects disadvantaged and minoritized communities, she said. 
 

Greater Impact on Disadvantaged Populations

Matsui called attention to the equity implications of climate change impacts on health. 

“If you have a community that does not have the infrastructure and access to resources, and that same community has a prevalence of asthma that is double that of their more advantaged and white counterparts, then the impacts of climate change are going to be amplified even more,” she said.

For example, a 2019 study found that the biggest predictor of the location of ragweed plants has to do with vacant lots and demolition of housing. Ragweed plants being more common in neighborhoods with vacant lots will disproportionately affect disadvantaged neighborhoods, she said. Another study found in Baltimore that mouse allergens — specifically urine — were a bigger cause of asthma in low-income children than were cockroach allergens. 

“It’s important to consider context,” including age, gender and social and behavioral context, she said. “We as pediatricians know that children are particularly vulnerable, and what happens to them has an effect across the lifespan.” 

Furthermore, pediatricians are aware that disadvantaged and minoritized communities lack infrastructure; often live in areas with greater air pollution; often have heat islands in their communities without protection, such as tree canopy; and may be at greater flooding risk. “Poverty is also associated with increased vulnerability” because of poorer housing and infrastructure, less education, less access to care, more preexisting health conditions and greater discrimination, she said.
 

Three Cornerstone Interventions

Interventions fall into three main buckets, Matsui said: mitigation, adaption, and resilience. 

“Mitigation means reducing greenhouse gas and air pollution production and trying to enhance sinks for greenhouse gases,” she said. Mitigation strategies primarily occur at the policy level, with improved regulation, treaties, and market-based approaches, such as carbon tax and cap and trade. 

Adaptation includes actions that lessen the impact on health and environment, such as infrastructure changes and implementation of air conditioning. Examples of climate change adaptation strategies also mostly come from policy but largely at state and local levels, where individual pediatricians have a greater voice and influence. These can include changes in urban planning to address heat islands, flooding risk, and public transportation’s contribution to air pollution and climate change. It can also include changes in housing regulation and policy and investments in healthcare, such as expanded Medicaid and health insurance and investing in disaster planning and readiness. 

“Resilience is a more holistic concept,” Matsui said, “which advocates for system-wide, multilevel changes and involves a range of strategies to enhance social, human, natural, physical, and financial capacities.”
 

What Pediatricians Can Do

Pediatricians have an important role to play when it comes to climate change and health impacts. 

“The first step is sort of understanding the complexity of climate change in terms of its potential health effects, but also being prepared to talk with our patients and their families about it,” Matsui said. “The second step is advocacy.” She drew attention to the February policy statement in Pediatrics that discusses precisely the ways in which pediatricians can leverage their expertise and credibility. 

“Pediatricians are ideal advocates with whom to partner and uplift youth and community voices working to advance zero-carbon energy policy and climate justice,” she said. “There are many opportunities to advocate for climate solution policies at the local, state, national, and even international level.” 

These roles can include educating elected officials and health insurance entities about the risks that climate change poses to allergies, asthma, and child health more broadly, as well as the benefits of local solutions, including improved air quality, tree canopy, and green space. “There are lots of opportunities to engage with the community, including speaking at public hearings, serving as an expert testimony, and writing letters to the editor,” she said. 

The impact of these efforts can be further maximized by working with other healthcare professionals. Lori Byron, MD, a pediatrician from Red Lodge, Montana, who heads the AAP Chapter Climate Advocates program, noted during Q&A that every AAP chapter in the country has climate advocates. She added that the AAP is the first medical board to have climate modules in their maintenance of certification specifically designed to incorporate climate change education into well visits.
 

Adjusting Clinical Care

Meanwhile, in patient care, Matsui acknowledged it can be frustrating to think about what a massive impact climate has and simultaneously challenging to engage families in discussions about it. However, a wide range of resources are available that can be provided to patients. 

“For a patient in front of you, being informed and prepared to talk about it is the first step to being able to assess their climate change risk and provide tailored guidance,” she said. Tailored guidance takes into account the child’s specific health situation and the risks they’re most likely to encounter, such as wildfire smoke, air pollution, longer pollen seasons, environmental allergens, or disruption of infrastructure. 

“If I am seeing a patient with asthma who is allergic to a particular pollen, I can anticipate that pollen may be present in higher levels of the future, and that the season for that pollen may be longer,” Matsui said. “So if I’m thinking about allergen immunotherapy for that patient, future risk may be something that would push the conversation and the shared decision-making” from possible consideration to more serious consideration, depending on the child’s age. 

“Another example is a patient with asthma, thinking about wildfire risk and having them prepared, because we know from data that wildfire air pollution is going to be worse for that child than pollution from other sources, and there are ways for them to be prepared,” Matsui said. For instance, having an HVAC system with a high-grade air filter (at least a MERV 13) will filter the air better if a wildfire causes smoke to descend over an area. Portable, less expensive HEPA filters are also an option if a family cannot upgrade their system, and wearing an N95 or N95-equivalent mask can also reduce the impact of high air pollution levels. 

An example of thinking about the impact of potential infrastructure disruption could be ensuring patients have enough of all their medications if they’re close to running out. “It’s important for them to always have think about their medications and get those refills ahead of a storm,” she said.
 

Additional Resources 

Understanding that pediatricians may not have time to discuss all these issues or have broader conversations about climate change during visits, Matsui highlighted the AAP website of resources on climate change. In addition to resources for pediatricians, such as a basic fact sheet about climate change impacts on children’s health and the technical report that informed the policy statement, the site has multiple resources for families:

• Climate Change Impact: Safeguarding Your Family’s Health and Well-being (video), How to Talk With Children About Climate Change, Climate Change & Children’s Health: AAP Policy Explained, Climate Checkup for Children’s Health: Little Changes With Big Impact, How Climate Change Can Make Children Sick: What Parents Need to Know, Climate Change & Wildfires: Why Kids Are Most at Risk, Climate Change, Extreme Weather & Children: What Families Need to Know, Extreme Heat & Air Pollution: Health Effects on Babies & Pregnant People, and

The following resources can also be helpful to pediatricians and/or families:

• Ready.gov, AirNow, Patient Exposure and the Air Quality Index, Protecting Vulnerable Patient Populations from Climate Hazards: A Referral Guide for Health Professionals from the US Department of Health and Human Services, Low Income Home Energy Assistance Program (LIHEAP), Weatherization Assistance Program, and the Disaster Supplemental Nutrition Assistance Program (D-SNAP)

In some states, Medicaid will provide or cover the cost of air conditioning and/or air filters.

The presentation did not involve external funding. Drs. Matsui and Moon had no disclosures. 
 

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

ORLANDO — It’s important for pediatricians not only to understand the causes and effects of climate change but also to know how to discuss this issue with families and make risk-based adjustments to their clinical practice based on the individual health and circumstances of each patient. That’s one of the key messages delivered at the annual meeting of the American Academy of Pediatrics (AAP) by Elizabeth C. Matsui, MD, MHS, professor of population health and pediatrics and director of the Center for Health and Environment Education and Research at the University of Texas at Austin Dell Medical School. 

“Even though climate change has been here and has been affecting health already for a while, it’s just really impossible to ignore right now,” she told attendees in a session focused on climate change impacts on allergies and asthma. “The challenge is connecting the dots between something that is much larger, or feels much larger, than the patient and the family that’s in front of you.” 

The reality, however, is that climate change is now impacting patients’ health on an individual level, and pediatricians have a responsibility to understand how that’s happening and to help their families prepare for it. 

“From the perspective of someone who went into medicine to practice and take care of the individual patient, I think it has been more difficult to connect those dots, and for the people in this room, it’s our job to connect those dots,” Matsui said. She also acknowledged that many of the solutions are frustratingly limited to the policy level and challenging to implement, “but it doesn’t mean that we can’t make a difference for the patients who are in front of us.” 

Charles Moon, MD, a pediatrician and Pediatric Environmental Health Fellow at the Children’s Environmental Health Center, Icahn School of Medicine at Mount Sinai, New York City, found the talk particularly helpful in providing information about both the broader issue and what it means on a local practice level. 

“The biggest takeaway is that more people and more pediatricians are tuning in to this issue and realizing the dangers,” Moon said. “It’s clear that a larger community is forming around this, and I think we are at the cusp where more and more people will be coming in. We are really focusing on taking all the data and trying to figure out solutions. I think the solutions orientation is the most important part.” 
 

Understanding the Big Picture

Matsui opened with a general discussion of the human causes of climate change and the effects on a global scale presently and in the future. For example, over the past 800,000 years, carbon dioxide levels have never been above 300 ppm, but they surpassed that threshold in 1911 and have reached 420 ppm today. The trapping of heat in Earth’s atmosphere caused by the increase in carbon dioxide and other greenhouse gases is leading to multiple phenomena that impact health, such as longer growing seasons; increased droughts, heat waves, and wildfire seasons; and higher temperatures. These changes, in turn, affect allergens and asthma.

Children are particularly vulnerable to climate change impacts because they have a higher risk for developing asthma, allergic disease, and infections, Matsui said. Childhood is a critical period for lung and immune development, and the Environmental Protection Agency’s 2023 Climate Change and Children’s Health and Well-Being report projects that an increase of 2° C in global warming will result in an additional 34,500 pediatric asthma cases and 228,000 allergic rhinitis cases per year, driven largely by predicted increases in ozone and 2.5-µm particulate matter. The report also forecasts an increase in 6240 asthma emergency department visits and 332 additional respiratory hospitalizations per year. 

“We know that these associations that we see between climate change exposures and poor respiratory health outcomes in kids are biologically plausible,” Matsui said. “They’re not just correlation without causation. A lot of the mechanisms for how air pollution, allergies, and other factors directly affect the lungs of the airway epithelium have been worked out.” 
 

An Increase in Allergens and Viral Infections

Pediatricians should prepare for anticipated growth in allergens and viral infections. The longer growing seasons mean that pollen seasons will also lengthen. Meanwhile, higher concentrations of carbon dioxide cause individual plants to produce more pollen. 

“As the winters get warmer, mice that might not be able to survive during the winter are surviving, and mice reproduce at a very rapid rate,” she said. “The increase in moisture means that dust mites, which absorb their water — they drink by absorbing humidity that’s in the air — will be present in higher concentrations, and their range will expand.”

Fungal and mold exposures are also increasing, not just outdoors but also indoors, “and there are all sorts of allergic and respiratory health consequences of fungal exposure,” Matsui said. As hurricanes and flooding increase, storm damage can also make indoor environments more conducive to fungal and mold growth. 

Extreme weather from climate change also affects infrastructure. “When there’s healthcare infrastructure disruption and other infrastructure disruption, it adds to the challenge,” she said. “It compounds all the other threat to health from climate change, so this overall problem of climate change and health is multidimensional and very complicated.”

Then there’s the impact of climate change on respiratory viruses, which are a major driver of asthma exacerbations, Matsui said. The greater variability in daytime temperatures affects environmental reservoirs, transmission patterns, geographical ranges, and seasonality of various respiratory pathogens. The prevalence of respiratory syncytial virus infections, for example, increases during humid periods. 

“This is coupled with the fact that the projected increases in air pollution increase susceptibility to respiratory virus infections,” Matsui said. “In fact, climate change and air pollution are inextricably linked.” 
 

Climate Change and Air Pollution

Climate disruption creates extreme weather patterns that then lead to worsening air quality due to high temperatures; heavier precipitation; and more forest fires, droughts, dust storms, thunderstorms, hurricanes, stagnation events, and other extreme weather. Matsui shared a map showing the substantial increase in days with stagnant air since 1973. During stagnation events, air pollution builds up in the atmosphere because of a stable air mass that remains over a region for several days, with low-level winds and no precipitation. 

The pollutants can then contribute to rising temperatures. Black carbon particulate matter released from the burning of forests and other biomass absorbs more solar radiation, further contributing to temperature increases. Data from the National Bureau of Economic Research has shown that the US made big strides in reducing air pollution from 2009 through 2016, but it began to reverse in 2016 as severe weather events picked up. 

Pediatricians need to be cognizant of the synergistic effect of these different impacts as well. “We oftentimes talk about these problems in a silo, so we may talk about air pollution and health effects, or allergens and health effects, or heat and health effects, but all of these interact with each other and further compound the health effects,” compared to just one of them in isolation, Matsui said.

For example, air pollution increases sensitivity to allergen exposure and increases reaction severity, which disrupts the immune tolerance to allergens. “Heat and air pollution also interact, and the combination of the two is more deadly than either one alone,” she said. 

Air pollution from wildfire smoke is also more toxic to the lungs than air pollution from other sources, so if there’s wildfire-based air pollution, the impact on respiratory hospitalizations is significantly greater. Even in places that would not otherwise be at risk for wildfires, the threat remains of air pollution from more distant fires, as New York City experienced from Canadian wildfires last year. 

“This is a problem that is not just isolated to the parts of the world where the wildfires are located,” Matsui said.

Moon, who practices in New York City, said he really appreciated Matsui’s perspectives and nuanced advice as a subspecialist “because it’s obvious that the way we deliver healthcare is going to have to change based on climate change.” He hopes to see more subspecialists from other pediatric areas getting involved in looking at climate impacts and providing nuanced advice about changing clinical care similar to the examples Matsui provided. 

Air pollution can also be deadly, as a landmark case in the United Kingdom revealed a few years ago when the court ruled that a child’s death from an asthma attack was directly due to air pollution. In addition to causing worse asthma symptoms and exacerbations, air pollution also adds to the risk of developing asthma and impedes lung growth, all of which disproportionately affects disadvantaged and minoritized communities, she said. 
 

Greater Impact on Disadvantaged Populations

Matsui called attention to the equity implications of climate change impacts on health. 

“If you have a community that does not have the infrastructure and access to resources, and that same community has a prevalence of asthma that is double that of their more advantaged and white counterparts, then the impacts of climate change are going to be amplified even more,” she said.

For example, a 2019 study found that the biggest predictor of the location of ragweed plants has to do with vacant lots and demolition of housing. Ragweed plants being more common in neighborhoods with vacant lots will disproportionately affect disadvantaged neighborhoods, she said. Another study found in Baltimore that mouse allergens — specifically urine — were a bigger cause of asthma in low-income children than were cockroach allergens. 

“It’s important to consider context,” including age, gender and social and behavioral context, she said. “We as pediatricians know that children are particularly vulnerable, and what happens to them has an effect across the lifespan.” 

Furthermore, pediatricians are aware that disadvantaged and minoritized communities lack infrastructure; often live in areas with greater air pollution; often have heat islands in their communities without protection, such as tree canopy; and may be at greater flooding risk. “Poverty is also associated with increased vulnerability” because of poorer housing and infrastructure, less education, less access to care, more preexisting health conditions and greater discrimination, she said.
 

Three Cornerstone Interventions

Interventions fall into three main buckets, Matsui said: mitigation, adaption, and resilience. 

“Mitigation means reducing greenhouse gas and air pollution production and trying to enhance sinks for greenhouse gases,” she said. Mitigation strategies primarily occur at the policy level, with improved regulation, treaties, and market-based approaches, such as carbon tax and cap and trade. 

Adaptation includes actions that lessen the impact on health and environment, such as infrastructure changes and implementation of air conditioning. Examples of climate change adaptation strategies also mostly come from policy but largely at state and local levels, where individual pediatricians have a greater voice and influence. These can include changes in urban planning to address heat islands, flooding risk, and public transportation’s contribution to air pollution and climate change. It can also include changes in housing regulation and policy and investments in healthcare, such as expanded Medicaid and health insurance and investing in disaster planning and readiness. 

“Resilience is a more holistic concept,” Matsui said, “which advocates for system-wide, multilevel changes and involves a range of strategies to enhance social, human, natural, physical, and financial capacities.”
 

What Pediatricians Can Do

Pediatricians have an important role to play when it comes to climate change and health impacts. 

“The first step is sort of understanding the complexity of climate change in terms of its potential health effects, but also being prepared to talk with our patients and their families about it,” Matsui said. “The second step is advocacy.” She drew attention to the February policy statement in Pediatrics that discusses precisely the ways in which pediatricians can leverage their expertise and credibility. 

“Pediatricians are ideal advocates with whom to partner and uplift youth and community voices working to advance zero-carbon energy policy and climate justice,” she said. “There are many opportunities to advocate for climate solution policies at the local, state, national, and even international level.” 

These roles can include educating elected officials and health insurance entities about the risks that climate change poses to allergies, asthma, and child health more broadly, as well as the benefits of local solutions, including improved air quality, tree canopy, and green space. “There are lots of opportunities to engage with the community, including speaking at public hearings, serving as an expert testimony, and writing letters to the editor,” she said. 

The impact of these efforts can be further maximized by working with other healthcare professionals. Lori Byron, MD, a pediatrician from Red Lodge, Montana, who heads the AAP Chapter Climate Advocates program, noted during Q&A that every AAP chapter in the country has climate advocates. She added that the AAP is the first medical board to have climate modules in their maintenance of certification specifically designed to incorporate climate change education into well visits.
 

Adjusting Clinical Care

Meanwhile, in patient care, Matsui acknowledged it can be frustrating to think about what a massive impact climate has and simultaneously challenging to engage families in discussions about it. However, a wide range of resources are available that can be provided to patients. 

“For a patient in front of you, being informed and prepared to talk about it is the first step to being able to assess their climate change risk and provide tailored guidance,” she said. Tailored guidance takes into account the child’s specific health situation and the risks they’re most likely to encounter, such as wildfire smoke, air pollution, longer pollen seasons, environmental allergens, or disruption of infrastructure. 

“If I am seeing a patient with asthma who is allergic to a particular pollen, I can anticipate that pollen may be present in higher levels of the future, and that the season for that pollen may be longer,” Matsui said. “So if I’m thinking about allergen immunotherapy for that patient, future risk may be something that would push the conversation and the shared decision-making” from possible consideration to more serious consideration, depending on the child’s age. 

“Another example is a patient with asthma, thinking about wildfire risk and having them prepared, because we know from data that wildfire air pollution is going to be worse for that child than pollution from other sources, and there are ways for them to be prepared,” Matsui said. For instance, having an HVAC system with a high-grade air filter (at least a MERV 13) will filter the air better if a wildfire causes smoke to descend over an area. Portable, less expensive HEPA filters are also an option if a family cannot upgrade their system, and wearing an N95 or N95-equivalent mask can also reduce the impact of high air pollution levels. 

An example of thinking about the impact of potential infrastructure disruption could be ensuring patients have enough of all their medications if they’re close to running out. “It’s important for them to always have think about their medications and get those refills ahead of a storm,” she said.
 

Additional Resources 

Understanding that pediatricians may not have time to discuss all these issues or have broader conversations about climate change during visits, Matsui highlighted the AAP website of resources on climate change. In addition to resources for pediatricians, such as a basic fact sheet about climate change impacts on children’s health and the technical report that informed the policy statement, the site has multiple resources for families:

• Climate Change Impact: Safeguarding Your Family’s Health and Well-being (video), How to Talk With Children About Climate Change, Climate Change & Children’s Health: AAP Policy Explained, Climate Checkup for Children’s Health: Little Changes With Big Impact, How Climate Change Can Make Children Sick: What Parents Need to Know, Climate Change & Wildfires: Why Kids Are Most at Risk, Climate Change, Extreme Weather & Children: What Families Need to Know, Extreme Heat & Air Pollution: Health Effects on Babies & Pregnant People, and

The following resources can also be helpful to pediatricians and/or families:

• Ready.gov, AirNow, Patient Exposure and the Air Quality Index, Protecting Vulnerable Patient Populations from Climate Hazards: A Referral Guide for Health Professionals from the US Department of Health and Human Services, Low Income Home Energy Assistance Program (LIHEAP), Weatherization Assistance Program, and the Disaster Supplemental Nutrition Assistance Program (D-SNAP)

In some states, Medicaid will provide or cover the cost of air conditioning and/or air filters.

The presentation did not involve external funding. Drs. Matsui and Moon had no disclosures. 
 

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

ORLANDO — It’s important for pediatricians not only to understand the causes and effects of climate change but also to know how to discuss this issue with families and make risk-based adjustments to their clinical practice based on the individual health and circumstances of each patient. That’s one of the key messages delivered at the annual meeting of the American Academy of Pediatrics (AAP) by Elizabeth C. Matsui, MD, MHS, professor of population health and pediatrics and director of the Center for Health and Environment Education and Research at the University of Texas at Austin Dell Medical School. 

“Even though climate change has been here and has been affecting health already for a while, it’s just really impossible to ignore right now,” she told attendees in a session focused on climate change impacts on allergies and asthma. “The challenge is connecting the dots between something that is much larger, or feels much larger, than the patient and the family that’s in front of you.” 

The reality, however, is that climate change is now impacting patients’ health on an individual level, and pediatricians have a responsibility to understand how that’s happening and to help their families prepare for it. 

“From the perspective of someone who went into medicine to practice and take care of the individual patient, I think it has been more difficult to connect those dots, and for the people in this room, it’s our job to connect those dots,” Matsui said. She also acknowledged that many of the solutions are frustratingly limited to the policy level and challenging to implement, “but it doesn’t mean that we can’t make a difference for the patients who are in front of us.” 

Charles Moon, MD, a pediatrician and Pediatric Environmental Health Fellow at the Children’s Environmental Health Center, Icahn School of Medicine at Mount Sinai, New York City, found the talk particularly helpful in providing information about both the broader issue and what it means on a local practice level. 

“The biggest takeaway is that more people and more pediatricians are tuning in to this issue and realizing the dangers,” Moon said. “It’s clear that a larger community is forming around this, and I think we are at the cusp where more and more people will be coming in. We are really focusing on taking all the data and trying to figure out solutions. I think the solutions orientation is the most important part.” 
 

Understanding the Big Picture

Matsui opened with a general discussion of the human causes of climate change and the effects on a global scale presently and in the future. For example, over the past 800,000 years, carbon dioxide levels have never been above 300 ppm, but they surpassed that threshold in 1911 and have reached 420 ppm today. The trapping of heat in Earth’s atmosphere caused by the increase in carbon dioxide and other greenhouse gases is leading to multiple phenomena that impact health, such as longer growing seasons; increased droughts, heat waves, and wildfire seasons; and higher temperatures. These changes, in turn, affect allergens and asthma.

Children are particularly vulnerable to climate change impacts because they have a higher risk for developing asthma, allergic disease, and infections, Matsui said. Childhood is a critical period for lung and immune development, and the Environmental Protection Agency’s 2023 Climate Change and Children’s Health and Well-Being report projects that an increase of 2° C in global warming will result in an additional 34,500 pediatric asthma cases and 228,000 allergic rhinitis cases per year, driven largely by predicted increases in ozone and 2.5-µm particulate matter. The report also forecasts an increase in 6240 asthma emergency department visits and 332 additional respiratory hospitalizations per year. 

“We know that these associations that we see between climate change exposures and poor respiratory health outcomes in kids are biologically plausible,” Matsui said. “They’re not just correlation without causation. A lot of the mechanisms for how air pollution, allergies, and other factors directly affect the lungs of the airway epithelium have been worked out.” 
 

An Increase in Allergens and Viral Infections

Pediatricians should prepare for anticipated growth in allergens and viral infections. The longer growing seasons mean that pollen seasons will also lengthen. Meanwhile, higher concentrations of carbon dioxide cause individual plants to produce more pollen. 

“As the winters get warmer, mice that might not be able to survive during the winter are surviving, and mice reproduce at a very rapid rate,” she said. “The increase in moisture means that dust mites, which absorb their water — they drink by absorbing humidity that’s in the air — will be present in higher concentrations, and their range will expand.”

Fungal and mold exposures are also increasing, not just outdoors but also indoors, “and there are all sorts of allergic and respiratory health consequences of fungal exposure,” Matsui said. As hurricanes and flooding increase, storm damage can also make indoor environments more conducive to fungal and mold growth. 

Extreme weather from climate change also affects infrastructure. “When there’s healthcare infrastructure disruption and other infrastructure disruption, it adds to the challenge,” she said. “It compounds all the other threat to health from climate change, so this overall problem of climate change and health is multidimensional and very complicated.”

Then there’s the impact of climate change on respiratory viruses, which are a major driver of asthma exacerbations, Matsui said. The greater variability in daytime temperatures affects environmental reservoirs, transmission patterns, geographical ranges, and seasonality of various respiratory pathogens. The prevalence of respiratory syncytial virus infections, for example, increases during humid periods. 

“This is coupled with the fact that the projected increases in air pollution increase susceptibility to respiratory virus infections,” Matsui said. “In fact, climate change and air pollution are inextricably linked.” 
 

Climate Change and Air Pollution

Climate disruption creates extreme weather patterns that then lead to worsening air quality due to high temperatures; heavier precipitation; and more forest fires, droughts, dust storms, thunderstorms, hurricanes, stagnation events, and other extreme weather. Matsui shared a map showing the substantial increase in days with stagnant air since 1973. During stagnation events, air pollution builds up in the atmosphere because of a stable air mass that remains over a region for several days, with low-level winds and no precipitation. 

The pollutants can then contribute to rising temperatures. Black carbon particulate matter released from the burning of forests and other biomass absorbs more solar radiation, further contributing to temperature increases. Data from the National Bureau of Economic Research has shown that the US made big strides in reducing air pollution from 2009 through 2016, but it began to reverse in 2016 as severe weather events picked up. 

Pediatricians need to be cognizant of the synergistic effect of these different impacts as well. “We oftentimes talk about these problems in a silo, so we may talk about air pollution and health effects, or allergens and health effects, or heat and health effects, but all of these interact with each other and further compound the health effects,” compared to just one of them in isolation, Matsui said.

For example, air pollution increases sensitivity to allergen exposure and increases reaction severity, which disrupts the immune tolerance to allergens. “Heat and air pollution also interact, and the combination of the two is more deadly than either one alone,” she said. 

Air pollution from wildfire smoke is also more toxic to the lungs than air pollution from other sources, so if there’s wildfire-based air pollution, the impact on respiratory hospitalizations is significantly greater. Even in places that would not otherwise be at risk for wildfires, the threat remains of air pollution from more distant fires, as New York City experienced from Canadian wildfires last year. 

“This is a problem that is not just isolated to the parts of the world where the wildfires are located,” Matsui said.

Moon, who practices in New York City, said he really appreciated Matsui’s perspectives and nuanced advice as a subspecialist “because it’s obvious that the way we deliver healthcare is going to have to change based on climate change.” He hopes to see more subspecialists from other pediatric areas getting involved in looking at climate impacts and providing nuanced advice about changing clinical care similar to the examples Matsui provided. 

Air pollution can also be deadly, as a landmark case in the United Kingdom revealed a few years ago when the court ruled that a child’s death from an asthma attack was directly due to air pollution. In addition to causing worse asthma symptoms and exacerbations, air pollution also adds to the risk of developing asthma and impedes lung growth, all of which disproportionately affects disadvantaged and minoritized communities, she said. 
 

Greater Impact on Disadvantaged Populations

Matsui called attention to the equity implications of climate change impacts on health. 

“If you have a community that does not have the infrastructure and access to resources, and that same community has a prevalence of asthma that is double that of their more advantaged and white counterparts, then the impacts of climate change are going to be amplified even more,” she said.

For example, a 2019 study found that the biggest predictor of the location of ragweed plants has to do with vacant lots and demolition of housing. Ragweed plants being more common in neighborhoods with vacant lots will disproportionately affect disadvantaged neighborhoods, she said. Another study found in Baltimore that mouse allergens — specifically urine — were a bigger cause of asthma in low-income children than were cockroach allergens. 

“It’s important to consider context,” including age, gender and social and behavioral context, she said. “We as pediatricians know that children are particularly vulnerable, and what happens to them has an effect across the lifespan.” 

Furthermore, pediatricians are aware that disadvantaged and minoritized communities lack infrastructure; often live in areas with greater air pollution; often have heat islands in their communities without protection, such as tree canopy; and may be at greater flooding risk. “Poverty is also associated with increased vulnerability” because of poorer housing and infrastructure, less education, less access to care, more preexisting health conditions and greater discrimination, she said.
 

Three Cornerstone Interventions

Interventions fall into three main buckets, Matsui said: mitigation, adaption, and resilience. 

“Mitigation means reducing greenhouse gas and air pollution production and trying to enhance sinks for greenhouse gases,” she said. Mitigation strategies primarily occur at the policy level, with improved regulation, treaties, and market-based approaches, such as carbon tax and cap and trade. 

Adaptation includes actions that lessen the impact on health and environment, such as infrastructure changes and implementation of air conditioning. Examples of climate change adaptation strategies also mostly come from policy but largely at state and local levels, where individual pediatricians have a greater voice and influence. These can include changes in urban planning to address heat islands, flooding risk, and public transportation’s contribution to air pollution and climate change. It can also include changes in housing regulation and policy and investments in healthcare, such as expanded Medicaid and health insurance and investing in disaster planning and readiness. 

“Resilience is a more holistic concept,” Matsui said, “which advocates for system-wide, multilevel changes and involves a range of strategies to enhance social, human, natural, physical, and financial capacities.”
 

What Pediatricians Can Do

Pediatricians have an important role to play when it comes to climate change and health impacts. 

“The first step is sort of understanding the complexity of climate change in terms of its potential health effects, but also being prepared to talk with our patients and their families about it,” Matsui said. “The second step is advocacy.” She drew attention to the February policy statement in Pediatrics that discusses precisely the ways in which pediatricians can leverage their expertise and credibility. 

“Pediatricians are ideal advocates with whom to partner and uplift youth and community voices working to advance zero-carbon energy policy and climate justice,” she said. “There are many opportunities to advocate for climate solution policies at the local, state, national, and even international level.” 

These roles can include educating elected officials and health insurance entities about the risks that climate change poses to allergies, asthma, and child health more broadly, as well as the benefits of local solutions, including improved air quality, tree canopy, and green space. “There are lots of opportunities to engage with the community, including speaking at public hearings, serving as an expert testimony, and writing letters to the editor,” she said. 

The impact of these efforts can be further maximized by working with other healthcare professionals. Lori Byron, MD, a pediatrician from Red Lodge, Montana, who heads the AAP Chapter Climate Advocates program, noted during Q&A that every AAP chapter in the country has climate advocates. She added that the AAP is the first medical board to have climate modules in their maintenance of certification specifically designed to incorporate climate change education into well visits.
 

Adjusting Clinical Care

Meanwhile, in patient care, Matsui acknowledged it can be frustrating to think about what a massive impact climate has and simultaneously challenging to engage families in discussions about it. However, a wide range of resources are available that can be provided to patients. 

“For a patient in front of you, being informed and prepared to talk about it is the first step to being able to assess their climate change risk and provide tailored guidance,” she said. Tailored guidance takes into account the child’s specific health situation and the risks they’re most likely to encounter, such as wildfire smoke, air pollution, longer pollen seasons, environmental allergens, or disruption of infrastructure. 

“If I am seeing a patient with asthma who is allergic to a particular pollen, I can anticipate that pollen may be present in higher levels of the future, and that the season for that pollen may be longer,” Matsui said. “So if I’m thinking about allergen immunotherapy for that patient, future risk may be something that would push the conversation and the shared decision-making” from possible consideration to more serious consideration, depending on the child’s age. 

“Another example is a patient with asthma, thinking about wildfire risk and having them prepared, because we know from data that wildfire air pollution is going to be worse for that child than pollution from other sources, and there are ways for them to be prepared,” Matsui said. For instance, having an HVAC system with a high-grade air filter (at least a MERV 13) will filter the air better if a wildfire causes smoke to descend over an area. Portable, less expensive HEPA filters are also an option if a family cannot upgrade their system, and wearing an N95 or N95-equivalent mask can also reduce the impact of high air pollution levels. 

An example of thinking about the impact of potential infrastructure disruption could be ensuring patients have enough of all their medications if they’re close to running out. “It’s important for them to always have think about their medications and get those refills ahead of a storm,” she said.
 

Additional Resources 

Understanding that pediatricians may not have time to discuss all these issues or have broader conversations about climate change during visits, Matsui highlighted the AAP website of resources on climate change. In addition to resources for pediatricians, such as a basic fact sheet about climate change impacts on children’s health and the technical report that informed the policy statement, the site has multiple resources for families:

• Climate Change Impact: Safeguarding Your Family’s Health and Well-being (video), How to Talk With Children About Climate Change, Climate Change & Children’s Health: AAP Policy Explained, Climate Checkup for Children’s Health: Little Changes With Big Impact, How Climate Change Can Make Children Sick: What Parents Need to Know, Climate Change & Wildfires: Why Kids Are Most at Risk, Climate Change, Extreme Weather & Children: What Families Need to Know, Extreme Heat & Air Pollution: Health Effects on Babies & Pregnant People, and

The following resources can also be helpful to pediatricians and/or families:

• Ready.gov, AirNow, Patient Exposure and the Air Quality Index, Protecting Vulnerable Patient Populations from Climate Hazards: A Referral Guide for Health Professionals from the US Department of Health and Human Services, Low Income Home Energy Assistance Program (LIHEAP), Weatherization Assistance Program, and the Disaster Supplemental Nutrition Assistance Program (D-SNAP)

In some states, Medicaid will provide or cover the cost of air conditioning and/or air filters.

The presentation did not involve external funding. Drs. Matsui and Moon had no disclosures. 
 

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

ORLANDO — More than half of youth improved after receiving a dose of naloxone by emergency medical services (EMS) after an emergency dispatch call, according to research presented at the American Academy of Pediatrics 2024 National Conference.

“Emergency responders or EMS are often the first to arrive to an opioid poisoning, and they’re often the first to give naloxone, a potentially lifesaving medication,” said Christopher E. Gaw, MD, MPH, MBE, assistant professor of pediatrics at The Ohio State University College of Medicine and an emergency medicine physician at Nationwide Children’s Hospital in Columbus, Ohio.

Ohio State University

“Our study highlights and underscores its safety of use in the prehospital setting, and this is also supported by other data,” Gaw said. “Efforts to support public distribution and education on naloxone can really help each and every one of us as individual citizens prevent pediatric harm from the opioid crisis.”

Additional research at the meeting showed that teens’ knowledge, attitudes, and confidence about recognizing overdoses and assisting with naloxone administration improved following a peer-to-peer training program, suggesting that teens can play an important role in reducing youth mortality from overdoses.

An average of 22 American teens died from overdose every week in 2022, and as counterfeit pill use has increased among youth, research has found that fentanyl was detected in 93% of overdose deaths with counterfeit pills, according to Talia Puzantian, PharmD, BCPP, of the Keck Graduate Institute School of Pharmacy, Claremont, California, who led the study on peer education. Yet a recent survey had found that less than a third of teens (30%) knew what naloxone was, and only 14% knew how to administer it.

“Ensuring that adolescents have easy and confidential access to naloxone is important and can save lives,” said Taylor Nichols, MD, assistant clinical professor at the University of California San Francisco and an emergency medicine and addiction medicine–certified physician. “I have had teen patients who have told me that they have had to use naloxone obtained from our clinic on friends when they have accidentally overdosed.”

University of California

EMS Naloxone Administration to Youth

EMS clinicians are often the first healthcare providers to respond to an opioid overdose or poisoning event, and evidence-based guidelines for EMS naloxone administration were developed in 2019 to support this intervention. Gaw’s team investigated the frequency and demographics of pediatric administration of naloxone.

They analyzed data from the National Emergency Medical Services Information System on EMS activations for administration of at least one dose of naloxone during 2022 to those aged 0-17. There were 6215 EMS pediatric administrations of naloxone that year, and in the vast majority of cases (82%), the patient had not received a naloxone injection prior to EMS’s arrival.

Most patients (79%) were aged 13-17 years, but 10% were in the 6-12 age group. The remaining patients included 6% infants younger than 1 year and 4% aged 6-12 years. Just over half were for males (55%), and most were dispatched to a home or residential setting (61%). One in five incidents (22%) occurred at a non-healthcare business, 9% on a street or highway, and the rest at a healthcare facility or another location.

Most of the incidents occurred in urban areas (86%), followed by rural (7%), suburban (6%), and wilderness (1.4%). More occurred in the US South (42%) than in the West (29%), Midwest (22%), or Northeast (7.5%).

A key takeaway of those demographic findings is that ingestions and accidental poisonings with opioids can occur in children of any age, Nichols said. “Every single home that has any opioids in the home should absolutely have naloxone immediately available as well,” he said. “Every single person who is prescribed opioids should also have naloxone available and accessible and to be sure that the naloxone is not expired or otherwise tampered with and update that every few years.” He noted that Narcan expiration was recently extended from 3 years to 4 years by the US Food and Drug Administration (FDA).

“I always advise that people who have opioid medications keep them stored safely and securely,” Nichols said. “However, I also acknowledge that even perfect systems fail and that people make mistakes and may accidentally leave medication out, within reach, or otherwise unsecured. If that happens, and someone were to intentionally or unintentionally get into that medication and potentially overdose as a result, we want to have that reversal medication immediately available to reverse the overdose.”

In nearly all cases (91%), EMS provided advanced life support, with only 7.5% patients receiving basic life support and 1.5% receiving specialty critical care. Just under a third (29%) of the dispatch calls were for “overdose/poisoning/ingestion.” Other dispatch calls included “unconscious/fainting/near-fainting” (21%) or “cardiac arrest/death” (17%), but the frequency of each dispatch label varied by age groups.

For example, 38% of calls for infants were for cardiac arrest, compared with 15% of calls for older teens and 18% of calls for 6-12 year olds. An overdose/poisoning dispatch was meanwhile more common for teens (32%) than for infants (13%), younger children (23%), and older children/tweens (18%). Other dispatch complaints included “sick person/person down/unknown problem” (12%) and “breathing problem” (5%).

A possible reason for these variations is that “an overdose might be mistaken for another medical emergency, or vice versa, because opioid poisonings can be challenging to recognize, especially in young children and in the pediatric population,” Gaw said. “Both the public and emergency responders should maintain a high level of suspicion” of possible overdose for children with the signs or symptoms of it, such as low breathing, unresponsiveness, or small pupils.

In most cases (87%), the patient was not in cardiac arrest, though the patient had entered cardiac arrest before EMS’s arrival in 11.5% of cases. Two thirds of cases only involved one dose of naloxone, while the other 33% involved two doses.

Ryan Marino, MD, an addiction medicine specialist and an associate professor of emergency medicine at Case Western Reserve University School of Medicine in Cleveland, Ohio, who was not involved in the study, took note of the high proportion of cases in which two doses were administered.

“While there is, in my professional opinion, almost no downside to giving naloxone in situations like this, and everybody should have it available and know how to use it, I would caution people on the risk of anchor bias, especially when more than two doses of naloxone are given, since we know that one should be an effective amount for any known opioid overdose,” Marino said. Anchoring bias refers to the tendency for individuals to rely more heavily on the first piece of information they receive about a topic or situation.

“For first responders and healthcare professionals, the importance of additional resuscitation measures like oxygenation and ventilation are just as crucial,” Marino said. “People should not be discouraged if someone doesn’t immediately respond to naloxone as overdose physiology can cause mental status to stay impaired for other reasons beyond direct drug effect, such as hypercarbia, but continue to seek and/or provide additional emergency care in these situations.”

Patients improved after one dose in just over half the cases (54%), and their conditions were unchanged in 46% of cases. There were only 11 cases in which the patient’s condition worsened after a naloxone dose (0.2%). Most of the cases (88%) were transported by EMS, and there were 13 total deaths at the scene (0.2%).

Nichols found the low incidence of worsening clinical status particularly striking. “This is further evidence of a critically important point — naloxone is purely an opioid antagonist, and only binds to opioid receptors, such that if a person has not overdosed on opioids or does not otherwise have opioids in their system, naloxone will not have a significant effect and will not cause them harm,” Nichols said.

“The most common causes of harm are due to rapid reversal of overdose and the potential risks involved in the rapid reversal of opioid effects and potentially precipitating withdrawal, and as this paper demonstrates, these are exceedingly rare,” he said. “Given that, we should have an incredibly low barrier to administer naloxone appropriately.”

The study was limited by inability to know how many true pediatric opioid poisonings are managed by EMS, so future research could look at linking EMS and emergency room hospital databases.
 

Improved Self-Efficacy in Teens

Another study showed that a peer-to-peer training program increased teens’ knowledge about overdoses from 34% before training to 79% after (P < .0001), and it substantially improved their confidence in recognizing an overdose and administering naloxone.

Nichols said the study shows the importance of ensuring “that adolescents know how to keep themselves and their friends safe in the case that they or anyone they know does end up using illicit substances which either intentionally or unintentionally contain opioids.”

This study assessed a training program with 206 students in a Los Angeles County high school who were trained by their peers between November 2023 and March 2024. The training included trends in teen overdose deaths, defining what opioids and fentanyl are, recognizing an overdose, and responding to one with naloxone.

The teens were an average 16 years old, about evenly split between boys and girls, and mostly in 11th (40%) or 12th (28%) grade, though nearly a third (29%) were 9th graders.

The students’ knowledge about fentanyl’s presence in counterfeit pills increased from 21% before the training to 68% afterward, and their correct identification of an overdose increased from 47% of participants to 90%.

The students’ confidence and attitudes toward helping with an overdose also improved substantially after the training. About two thirds agreed that non-medical people should be able to carry naloxone before the training, and that rose to 88% agreeing after the training. The proportion who agreed they would be willing to assist in an overdose rose from 77% before to 89% after training.

More dramatically, the teens’ confidence after training more than doubled in recognizing an overdose (from 31% to 81%) and more than tripled in their ability to give naloxone during an overdose (from 26% to 83%).

“The critical piece to keep in mind is that the concern about opioid overdose is respiratory depression leading to a lack of oxygen getting to the brain,” Nichols explained. “In the event of an overdose, time is brain — the longer the brain is deprived of oxygen, the lower the chance of survival. There is no specific time at which naloxone would become less effective at reversing an overdose.”

Therefore, people do not need to know the exact time that someone may have overdosed or how long they have been passed out in order to administer naloxone, he said. “The sooner naloxone is administered to someone who is unresponsive and who may have overdosed on opioids, the higher the likelihood of a successful reversal of an overdose and of saving a life.”

The peer-to-peer program was sponsored by the CARLOW Center for Medical Innovation, and the EMS study used no external funding. The authors of both studies and Marino had no disclosures. Nichols has consulted or clinically advised TV shows and health tech startup companies and has no disclosures related to naloxone or the pharmaceutical industry.
 

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

ORLANDO — More than half of youth improved after receiving a dose of naloxone by emergency medical services (EMS) after an emergency dispatch call, according to research presented at the American Academy of Pediatrics 2024 National Conference.

“Emergency responders or EMS are often the first to arrive to an opioid poisoning, and they’re often the first to give naloxone, a potentially lifesaving medication,” said Christopher E. Gaw, MD, MPH, MBE, assistant professor of pediatrics at The Ohio State University College of Medicine and an emergency medicine physician at Nationwide Children’s Hospital in Columbus, Ohio.

Ohio State University

“Our study highlights and underscores its safety of use in the prehospital setting, and this is also supported by other data,” Gaw said. “Efforts to support public distribution and education on naloxone can really help each and every one of us as individual citizens prevent pediatric harm from the opioid crisis.”

Additional research at the meeting showed that teens’ knowledge, attitudes, and confidence about recognizing overdoses and assisting with naloxone administration improved following a peer-to-peer training program, suggesting that teens can play an important role in reducing youth mortality from overdoses.

An average of 22 American teens died from overdose every week in 2022, and as counterfeit pill use has increased among youth, research has found that fentanyl was detected in 93% of overdose deaths with counterfeit pills, according to Talia Puzantian, PharmD, BCPP, of the Keck Graduate Institute School of Pharmacy, Claremont, California, who led the study on peer education. Yet a recent survey had found that less than a third of teens (30%) knew what naloxone was, and only 14% knew how to administer it.

“Ensuring that adolescents have easy and confidential access to naloxone is important and can save lives,” said Taylor Nichols, MD, assistant clinical professor at the University of California San Francisco and an emergency medicine and addiction medicine–certified physician. “I have had teen patients who have told me that they have had to use naloxone obtained from our clinic on friends when they have accidentally overdosed.”

University of California

EMS Naloxone Administration to Youth

EMS clinicians are often the first healthcare providers to respond to an opioid overdose or poisoning event, and evidence-based guidelines for EMS naloxone administration were developed in 2019 to support this intervention. Gaw’s team investigated the frequency and demographics of pediatric administration of naloxone.

They analyzed data from the National Emergency Medical Services Information System on EMS activations for administration of at least one dose of naloxone during 2022 to those aged 0-17. There were 6215 EMS pediatric administrations of naloxone that year, and in the vast majority of cases (82%), the patient had not received a naloxone injection prior to EMS’s arrival.

Most patients (79%) were aged 13-17 years, but 10% were in the 6-12 age group. The remaining patients included 6% infants younger than 1 year and 4% aged 6-12 years. Just over half were for males (55%), and most were dispatched to a home or residential setting (61%). One in five incidents (22%) occurred at a non-healthcare business, 9% on a street or highway, and the rest at a healthcare facility or another location.

Most of the incidents occurred in urban areas (86%), followed by rural (7%), suburban (6%), and wilderness (1.4%). More occurred in the US South (42%) than in the West (29%), Midwest (22%), or Northeast (7.5%).

A key takeaway of those demographic findings is that ingestions and accidental poisonings with opioids can occur in children of any age, Nichols said. “Every single home that has any opioids in the home should absolutely have naloxone immediately available as well,” he said. “Every single person who is prescribed opioids should also have naloxone available and accessible and to be sure that the naloxone is not expired or otherwise tampered with and update that every few years.” He noted that Narcan expiration was recently extended from 3 years to 4 years by the US Food and Drug Administration (FDA).

“I always advise that people who have opioid medications keep them stored safely and securely,” Nichols said. “However, I also acknowledge that even perfect systems fail and that people make mistakes and may accidentally leave medication out, within reach, or otherwise unsecured. If that happens, and someone were to intentionally or unintentionally get into that medication and potentially overdose as a result, we want to have that reversal medication immediately available to reverse the overdose.”

In nearly all cases (91%), EMS provided advanced life support, with only 7.5% patients receiving basic life support and 1.5% receiving specialty critical care. Just under a third (29%) of the dispatch calls were for “overdose/poisoning/ingestion.” Other dispatch calls included “unconscious/fainting/near-fainting” (21%) or “cardiac arrest/death” (17%), but the frequency of each dispatch label varied by age groups.

For example, 38% of calls for infants were for cardiac arrest, compared with 15% of calls for older teens and 18% of calls for 6-12 year olds. An overdose/poisoning dispatch was meanwhile more common for teens (32%) than for infants (13%), younger children (23%), and older children/tweens (18%). Other dispatch complaints included “sick person/person down/unknown problem” (12%) and “breathing problem” (5%).

A possible reason for these variations is that “an overdose might be mistaken for another medical emergency, or vice versa, because opioid poisonings can be challenging to recognize, especially in young children and in the pediatric population,” Gaw said. “Both the public and emergency responders should maintain a high level of suspicion” of possible overdose for children with the signs or symptoms of it, such as low breathing, unresponsiveness, or small pupils.

In most cases (87%), the patient was not in cardiac arrest, though the patient had entered cardiac arrest before EMS’s arrival in 11.5% of cases. Two thirds of cases only involved one dose of naloxone, while the other 33% involved two doses.

Ryan Marino, MD, an addiction medicine specialist and an associate professor of emergency medicine at Case Western Reserve University School of Medicine in Cleveland, Ohio, who was not involved in the study, took note of the high proportion of cases in which two doses were administered.

“While there is, in my professional opinion, almost no downside to giving naloxone in situations like this, and everybody should have it available and know how to use it, I would caution people on the risk of anchor bias, especially when more than two doses of naloxone are given, since we know that one should be an effective amount for any known opioid overdose,” Marino said. Anchoring bias refers to the tendency for individuals to rely more heavily on the first piece of information they receive about a topic or situation.

“For first responders and healthcare professionals, the importance of additional resuscitation measures like oxygenation and ventilation are just as crucial,” Marino said. “People should not be discouraged if someone doesn’t immediately respond to naloxone as overdose physiology can cause mental status to stay impaired for other reasons beyond direct drug effect, such as hypercarbia, but continue to seek and/or provide additional emergency care in these situations.”

Patients improved after one dose in just over half the cases (54%), and their conditions were unchanged in 46% of cases. There were only 11 cases in which the patient’s condition worsened after a naloxone dose (0.2%). Most of the cases (88%) were transported by EMS, and there were 13 total deaths at the scene (0.2%).

Nichols found the low incidence of worsening clinical status particularly striking. “This is further evidence of a critically important point — naloxone is purely an opioid antagonist, and only binds to opioid receptors, such that if a person has not overdosed on opioids or does not otherwise have opioids in their system, naloxone will not have a significant effect and will not cause them harm,” Nichols said.

“The most common causes of harm are due to rapid reversal of overdose and the potential risks involved in the rapid reversal of opioid effects and potentially precipitating withdrawal, and as this paper demonstrates, these are exceedingly rare,” he said. “Given that, we should have an incredibly low barrier to administer naloxone appropriately.”

The study was limited by inability to know how many true pediatric opioid poisonings are managed by EMS, so future research could look at linking EMS and emergency room hospital databases.
 

Improved Self-Efficacy in Teens

Another study showed that a peer-to-peer training program increased teens’ knowledge about overdoses from 34% before training to 79% after (P < .0001), and it substantially improved their confidence in recognizing an overdose and administering naloxone.

Nichols said the study shows the importance of ensuring “that adolescents know how to keep themselves and their friends safe in the case that they or anyone they know does end up using illicit substances which either intentionally or unintentionally contain opioids.”

This study assessed a training program with 206 students in a Los Angeles County high school who were trained by their peers between November 2023 and March 2024. The training included trends in teen overdose deaths, defining what opioids and fentanyl are, recognizing an overdose, and responding to one with naloxone.

The teens were an average 16 years old, about evenly split between boys and girls, and mostly in 11th (40%) or 12th (28%) grade, though nearly a third (29%) were 9th graders.

The students’ knowledge about fentanyl’s presence in counterfeit pills increased from 21% before the training to 68% afterward, and their correct identification of an overdose increased from 47% of participants to 90%.

The students’ confidence and attitudes toward helping with an overdose also improved substantially after the training. About two thirds agreed that non-medical people should be able to carry naloxone before the training, and that rose to 88% agreeing after the training. The proportion who agreed they would be willing to assist in an overdose rose from 77% before to 89% after training.

More dramatically, the teens’ confidence after training more than doubled in recognizing an overdose (from 31% to 81%) and more than tripled in their ability to give naloxone during an overdose (from 26% to 83%).

“The critical piece to keep in mind is that the concern about opioid overdose is respiratory depression leading to a lack of oxygen getting to the brain,” Nichols explained. “In the event of an overdose, time is brain — the longer the brain is deprived of oxygen, the lower the chance of survival. There is no specific time at which naloxone would become less effective at reversing an overdose.”

Therefore, people do not need to know the exact time that someone may have overdosed or how long they have been passed out in order to administer naloxone, he said. “The sooner naloxone is administered to someone who is unresponsive and who may have overdosed on opioids, the higher the likelihood of a successful reversal of an overdose and of saving a life.”

The peer-to-peer program was sponsored by the CARLOW Center for Medical Innovation, and the EMS study used no external funding. The authors of both studies and Marino had no disclosures. Nichols has consulted or clinically advised TV shows and health tech startup companies and has no disclosures related to naloxone or the pharmaceutical industry.
 

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

ORLANDO — More than half of youth improved after receiving a dose of naloxone by emergency medical services (EMS) after an emergency dispatch call, according to research presented at the American Academy of Pediatrics 2024 National Conference.

“Emergency responders or EMS are often the first to arrive to an opioid poisoning, and they’re often the first to give naloxone, a potentially lifesaving medication,” said Christopher E. Gaw, MD, MPH, MBE, assistant professor of pediatrics at The Ohio State University College of Medicine and an emergency medicine physician at Nationwide Children’s Hospital in Columbus, Ohio.

Ohio State University

“Our study highlights and underscores its safety of use in the prehospital setting, and this is also supported by other data,” Gaw said. “Efforts to support public distribution and education on naloxone can really help each and every one of us as individual citizens prevent pediatric harm from the opioid crisis.”

Additional research at the meeting showed that teens’ knowledge, attitudes, and confidence about recognizing overdoses and assisting with naloxone administration improved following a peer-to-peer training program, suggesting that teens can play an important role in reducing youth mortality from overdoses.

An average of 22 American teens died from overdose every week in 2022, and as counterfeit pill use has increased among youth, research has found that fentanyl was detected in 93% of overdose deaths with counterfeit pills, according to Talia Puzantian, PharmD, BCPP, of the Keck Graduate Institute School of Pharmacy, Claremont, California, who led the study on peer education. Yet a recent survey had found that less than a third of teens (30%) knew what naloxone was, and only 14% knew how to administer it.

“Ensuring that adolescents have easy and confidential access to naloxone is important and can save lives,” said Taylor Nichols, MD, assistant clinical professor at the University of California San Francisco and an emergency medicine and addiction medicine–certified physician. “I have had teen patients who have told me that they have had to use naloxone obtained from our clinic on friends when they have accidentally overdosed.”

University of California

EMS Naloxone Administration to Youth

EMS clinicians are often the first healthcare providers to respond to an opioid overdose or poisoning event, and evidence-based guidelines for EMS naloxone administration were developed in 2019 to support this intervention. Gaw’s team investigated the frequency and demographics of pediatric administration of naloxone.

They analyzed data from the National Emergency Medical Services Information System on EMS activations for administration of at least one dose of naloxone during 2022 to those aged 0-17. There were 6215 EMS pediatric administrations of naloxone that year, and in the vast majority of cases (82%), the patient had not received a naloxone injection prior to EMS’s arrival.

Most patients (79%) were aged 13-17 years, but 10% were in the 6-12 age group. The remaining patients included 6% infants younger than 1 year and 4% aged 6-12 years. Just over half were for males (55%), and most were dispatched to a home or residential setting (61%). One in five incidents (22%) occurred at a non-healthcare business, 9% on a street or highway, and the rest at a healthcare facility or another location.

Most of the incidents occurred in urban areas (86%), followed by rural (7%), suburban (6%), and wilderness (1.4%). More occurred in the US South (42%) than in the West (29%), Midwest (22%), or Northeast (7.5%).

A key takeaway of those demographic findings is that ingestions and accidental poisonings with opioids can occur in children of any age, Nichols said. “Every single home that has any opioids in the home should absolutely have naloxone immediately available as well,” he said. “Every single person who is prescribed opioids should also have naloxone available and accessible and to be sure that the naloxone is not expired or otherwise tampered with and update that every few years.” He noted that Narcan expiration was recently extended from 3 years to 4 years by the US Food and Drug Administration (FDA).

“I always advise that people who have opioid medications keep them stored safely and securely,” Nichols said. “However, I also acknowledge that even perfect systems fail and that people make mistakes and may accidentally leave medication out, within reach, or otherwise unsecured. If that happens, and someone were to intentionally or unintentionally get into that medication and potentially overdose as a result, we want to have that reversal medication immediately available to reverse the overdose.”

In nearly all cases (91%), EMS provided advanced life support, with only 7.5% patients receiving basic life support and 1.5% receiving specialty critical care. Just under a third (29%) of the dispatch calls were for “overdose/poisoning/ingestion.” Other dispatch calls included “unconscious/fainting/near-fainting” (21%) or “cardiac arrest/death” (17%), but the frequency of each dispatch label varied by age groups.

For example, 38% of calls for infants were for cardiac arrest, compared with 15% of calls for older teens and 18% of calls for 6-12 year olds. An overdose/poisoning dispatch was meanwhile more common for teens (32%) than for infants (13%), younger children (23%), and older children/tweens (18%). Other dispatch complaints included “sick person/person down/unknown problem” (12%) and “breathing problem” (5%).

A possible reason for these variations is that “an overdose might be mistaken for another medical emergency, or vice versa, because opioid poisonings can be challenging to recognize, especially in young children and in the pediatric population,” Gaw said. “Both the public and emergency responders should maintain a high level of suspicion” of possible overdose for children with the signs or symptoms of it, such as low breathing, unresponsiveness, or small pupils.

In most cases (87%), the patient was not in cardiac arrest, though the patient had entered cardiac arrest before EMS’s arrival in 11.5% of cases. Two thirds of cases only involved one dose of naloxone, while the other 33% involved two doses.

Ryan Marino, MD, an addiction medicine specialist and an associate professor of emergency medicine at Case Western Reserve University School of Medicine in Cleveland, Ohio, who was not involved in the study, took note of the high proportion of cases in which two doses were administered.

“While there is, in my professional opinion, almost no downside to giving naloxone in situations like this, and everybody should have it available and know how to use it, I would caution people on the risk of anchor bias, especially when more than two doses of naloxone are given, since we know that one should be an effective amount for any known opioid overdose,” Marino said. Anchoring bias refers to the tendency for individuals to rely more heavily on the first piece of information they receive about a topic or situation.

“For first responders and healthcare professionals, the importance of additional resuscitation measures like oxygenation and ventilation are just as crucial,” Marino said. “People should not be discouraged if someone doesn’t immediately respond to naloxone as overdose physiology can cause mental status to stay impaired for other reasons beyond direct drug effect, such as hypercarbia, but continue to seek and/or provide additional emergency care in these situations.”

Patients improved after one dose in just over half the cases (54%), and their conditions were unchanged in 46% of cases. There were only 11 cases in which the patient’s condition worsened after a naloxone dose (0.2%). Most of the cases (88%) were transported by EMS, and there were 13 total deaths at the scene (0.2%).

Nichols found the low incidence of worsening clinical status particularly striking. “This is further evidence of a critically important point — naloxone is purely an opioid antagonist, and only binds to opioid receptors, such that if a person has not overdosed on opioids or does not otherwise have opioids in their system, naloxone will not have a significant effect and will not cause them harm,” Nichols said.

“The most common causes of harm are due to rapid reversal of overdose and the potential risks involved in the rapid reversal of opioid effects and potentially precipitating withdrawal, and as this paper demonstrates, these are exceedingly rare,” he said. “Given that, we should have an incredibly low barrier to administer naloxone appropriately.”

The study was limited by inability to know how many true pediatric opioid poisonings are managed by EMS, so future research could look at linking EMS and emergency room hospital databases.
 

Improved Self-Efficacy in Teens

Another study showed that a peer-to-peer training program increased teens’ knowledge about overdoses from 34% before training to 79% after (P < .0001), and it substantially improved their confidence in recognizing an overdose and administering naloxone.

Nichols said the study shows the importance of ensuring “that adolescents know how to keep themselves and their friends safe in the case that they or anyone they know does end up using illicit substances which either intentionally or unintentionally contain opioids.”

This study assessed a training program with 206 students in a Los Angeles County high school who were trained by their peers between November 2023 and March 2024. The training included trends in teen overdose deaths, defining what opioids and fentanyl are, recognizing an overdose, and responding to one with naloxone.

The teens were an average 16 years old, about evenly split between boys and girls, and mostly in 11th (40%) or 12th (28%) grade, though nearly a third (29%) were 9th graders.

The students’ knowledge about fentanyl’s presence in counterfeit pills increased from 21% before the training to 68% afterward, and their correct identification of an overdose increased from 47% of participants to 90%.

The students’ confidence and attitudes toward helping with an overdose also improved substantially after the training. About two thirds agreed that non-medical people should be able to carry naloxone before the training, and that rose to 88% agreeing after the training. The proportion who agreed they would be willing to assist in an overdose rose from 77% before to 89% after training.

More dramatically, the teens’ confidence after training more than doubled in recognizing an overdose (from 31% to 81%) and more than tripled in their ability to give naloxone during an overdose (from 26% to 83%).

“The critical piece to keep in mind is that the concern about opioid overdose is respiratory depression leading to a lack of oxygen getting to the brain,” Nichols explained. “In the event of an overdose, time is brain — the longer the brain is deprived of oxygen, the lower the chance of survival. There is no specific time at which naloxone would become less effective at reversing an overdose.”

Therefore, people do not need to know the exact time that someone may have overdosed or how long they have been passed out in order to administer naloxone, he said. “The sooner naloxone is administered to someone who is unresponsive and who may have overdosed on opioids, the higher the likelihood of a successful reversal of an overdose and of saving a life.”

The peer-to-peer program was sponsored by the CARLOW Center for Medical Innovation, and the EMS study used no external funding. The authors of both studies and Marino had no disclosures. Nichols has consulted or clinically advised TV shows and health tech startup companies and has no disclosures related to naloxone or the pharmaceutical industry.
 

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

BOSTON — With the remarkable advances made in therapy over the past decade, many patients with cystic fibrosis (CF) can expect to survive into their 50s and even well beyond. But as patients with CF live longer, they are increasingly likely to develop complications such as cardiovascular diseases (CVDs) that beset many older adults. And as evidence from a new study suggests, there is an increasing need for cardiovascular screening and specialized cardiac care for these patients.

Among more than 83,000 patients with CF hospitalized for any reason from 2016 through 2021, less than 1% of patients had a cardiac cause listed, but in unadjusted analyses, these patients had a more than twofold risk for in-hospital death than those with CF hospitalized for other causes, reported Adnan Bhat, MD, assistant professor of hospital medicine at the University of Florida, Gainesville.

Although the excess mortality was no longer statistically significant in analyses adjusted for potential confounding factors, the data highlight a trend that requires further exploration, he said during an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).

“There’s a trend for people with cystic fibrosis admitted for cardiac causes to have a higher in-hospital mortality and increased rate of discharge to nursing facilities, especially for patients admitted for heart failure. The clinical implication is that there is an increased need to start screening for cardiovascular risk factors,” he said.
 

National Database Sample

Bhat and colleagues conducted a retrospective study using the National Inpatient Sample database to identify all hospitalizations among patients with CF in the United States from 2016 through 2021.

They included all hospitalizations with a principal diagnosis code for atrial fibrillation, heart failure, or myocardial infarction.

Of 83,250 total hospitalizations during the study period, 415 (0.5%) were for primary cardiac causes. These included 170 hospitalizations for atrial fibrillation, 95 for heart failure, and 150 for myocardial infarction.

Patients hospitalized for cardiac causes had a higher mean age (59.5 vs 34.5 years) and more comorbidities than patients hospitalized for other causes. These comorbidities included hyperlipidemia, chronic kidney disease, obesity, and a family history of coronary artery disease.

In all, 5% of patients hospitalized for cardiac cause died in hospital, compared with 2% of patients hospitalized for other reasons (P = .044).

However, in logistic regression analyses adjusting for age, sex, and race, this difference was no longer significant.

Similarly, an unadjusted analysis showed that patients with cardiac disease were twice as likely to be discharged to a nursing facility (8% vs 4%, respectively), but this difference too disappeared in adjusted analyses.

The risk for in-hospital mortality appeared to be highest among those patients with a primary diagnosis of heart failure, who had an 11% rate of in-hospital death, compared with 2% among patients with CF hospitalized for other causes.

The total number of deaths was too small, however, to allow for regression analysis, Bhat said.

Nonetheless, taken together, the data indicate a trend toward increased mortality from cardiovascular causes among older patients with CF, as well as the need for further research into the cardiovascular health of these patients, Bhat concluded.
 

Better Nutrition, Higher Risk

In an interview, Yuqing A. Gao, MD, from the Santa Monica Pulmonary Sleep Clinic in California, who was not involved in the study, commented that with the advent of elexacaftor/tezacaftor/ivacaftor modulator therapy, patients with CF tend to have increases in body mass index and improved nutritional intake and absorption, which in turn could increase hyperlipidemia and other factors that might in turn contribute to increased CVD risk.

“It’s really an interesting area of research, and there’s hope that this will bring more focus on how to better screen [for CVD risk] because that’s something that’s very much not known at this time,” she said.

Gao was co-moderator for the session where Bhat presented the data. Bhat did not report a study funding source. Bhat and Gao reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

BOSTON — With the remarkable advances made in therapy over the past decade, many patients with cystic fibrosis (CF) can expect to survive into their 50s and even well beyond. But as patients with CF live longer, they are increasingly likely to develop complications such as cardiovascular diseases (CVDs) that beset many older adults. And as evidence from a new study suggests, there is an increasing need for cardiovascular screening and specialized cardiac care for these patients.

Among more than 83,000 patients with CF hospitalized for any reason from 2016 through 2021, less than 1% of patients had a cardiac cause listed, but in unadjusted analyses, these patients had a more than twofold risk for in-hospital death than those with CF hospitalized for other causes, reported Adnan Bhat, MD, assistant professor of hospital medicine at the University of Florida, Gainesville.

Although the excess mortality was no longer statistically significant in analyses adjusted for potential confounding factors, the data highlight a trend that requires further exploration, he said during an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).

“There’s a trend for people with cystic fibrosis admitted for cardiac causes to have a higher in-hospital mortality and increased rate of discharge to nursing facilities, especially for patients admitted for heart failure. The clinical implication is that there is an increased need to start screening for cardiovascular risk factors,” he said.
 

National Database Sample

Bhat and colleagues conducted a retrospective study using the National Inpatient Sample database to identify all hospitalizations among patients with CF in the United States from 2016 through 2021.

They included all hospitalizations with a principal diagnosis code for atrial fibrillation, heart failure, or myocardial infarction.

Of 83,250 total hospitalizations during the study period, 415 (0.5%) were for primary cardiac causes. These included 170 hospitalizations for atrial fibrillation, 95 for heart failure, and 150 for myocardial infarction.

Patients hospitalized for cardiac causes had a higher mean age (59.5 vs 34.5 years) and more comorbidities than patients hospitalized for other causes. These comorbidities included hyperlipidemia, chronic kidney disease, obesity, and a family history of coronary artery disease.

In all, 5% of patients hospitalized for cardiac cause died in hospital, compared with 2% of patients hospitalized for other reasons (P = .044).

However, in logistic regression analyses adjusting for age, sex, and race, this difference was no longer significant.

Similarly, an unadjusted analysis showed that patients with cardiac disease were twice as likely to be discharged to a nursing facility (8% vs 4%, respectively), but this difference too disappeared in adjusted analyses.

The risk for in-hospital mortality appeared to be highest among those patients with a primary diagnosis of heart failure, who had an 11% rate of in-hospital death, compared with 2% among patients with CF hospitalized for other causes.

The total number of deaths was too small, however, to allow for regression analysis, Bhat said.

Nonetheless, taken together, the data indicate a trend toward increased mortality from cardiovascular causes among older patients with CF, as well as the need for further research into the cardiovascular health of these patients, Bhat concluded.
 

Better Nutrition, Higher Risk

In an interview, Yuqing A. Gao, MD, from the Santa Monica Pulmonary Sleep Clinic in California, who was not involved in the study, commented that with the advent of elexacaftor/tezacaftor/ivacaftor modulator therapy, patients with CF tend to have increases in body mass index and improved nutritional intake and absorption, which in turn could increase hyperlipidemia and other factors that might in turn contribute to increased CVD risk.

“It’s really an interesting area of research, and there’s hope that this will bring more focus on how to better screen [for CVD risk] because that’s something that’s very much not known at this time,” she said.

Gao was co-moderator for the session where Bhat presented the data. Bhat did not report a study funding source. Bhat and Gao reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

BOSTON — With the remarkable advances made in therapy over the past decade, many patients with cystic fibrosis (CF) can expect to survive into their 50s and even well beyond. But as patients with CF live longer, they are increasingly likely to develop complications such as cardiovascular diseases (CVDs) that beset many older adults. And as evidence from a new study suggests, there is an increasing need for cardiovascular screening and specialized cardiac care for these patients.

Among more than 83,000 patients with CF hospitalized for any reason from 2016 through 2021, less than 1% of patients had a cardiac cause listed, but in unadjusted analyses, these patients had a more than twofold risk for in-hospital death than those with CF hospitalized for other causes, reported Adnan Bhat, MD, assistant professor of hospital medicine at the University of Florida, Gainesville.

Although the excess mortality was no longer statistically significant in analyses adjusted for potential confounding factors, the data highlight a trend that requires further exploration, he said during an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).

“There’s a trend for people with cystic fibrosis admitted for cardiac causes to have a higher in-hospital mortality and increased rate of discharge to nursing facilities, especially for patients admitted for heart failure. The clinical implication is that there is an increased need to start screening for cardiovascular risk factors,” he said.
 

National Database Sample

Bhat and colleagues conducted a retrospective study using the National Inpatient Sample database to identify all hospitalizations among patients with CF in the United States from 2016 through 2021.

They included all hospitalizations with a principal diagnosis code for atrial fibrillation, heart failure, or myocardial infarction.

Of 83,250 total hospitalizations during the study period, 415 (0.5%) were for primary cardiac causes. These included 170 hospitalizations for atrial fibrillation, 95 for heart failure, and 150 for myocardial infarction.

Patients hospitalized for cardiac causes had a higher mean age (59.5 vs 34.5 years) and more comorbidities than patients hospitalized for other causes. These comorbidities included hyperlipidemia, chronic kidney disease, obesity, and a family history of coronary artery disease.

In all, 5% of patients hospitalized for cardiac cause died in hospital, compared with 2% of patients hospitalized for other reasons (P = .044).

However, in logistic regression analyses adjusting for age, sex, and race, this difference was no longer significant.

Similarly, an unadjusted analysis showed that patients with cardiac disease were twice as likely to be discharged to a nursing facility (8% vs 4%, respectively), but this difference too disappeared in adjusted analyses.

The risk for in-hospital mortality appeared to be highest among those patients with a primary diagnosis of heart failure, who had an 11% rate of in-hospital death, compared with 2% among patients with CF hospitalized for other causes.

The total number of deaths was too small, however, to allow for regression analysis, Bhat said.

Nonetheless, taken together, the data indicate a trend toward increased mortality from cardiovascular causes among older patients with CF, as well as the need for further research into the cardiovascular health of these patients, Bhat concluded.
 

Better Nutrition, Higher Risk

In an interview, Yuqing A. Gao, MD, from the Santa Monica Pulmonary Sleep Clinic in California, who was not involved in the study, commented that with the advent of elexacaftor/tezacaftor/ivacaftor modulator therapy, patients with CF tend to have increases in body mass index and improved nutritional intake and absorption, which in turn could increase hyperlipidemia and other factors that might in turn contribute to increased CVD risk.

“It’s really an interesting area of research, and there’s hope that this will bring more focus on how to better screen [for CVD risk] because that’s something that’s very much not known at this time,” she said.

Gao was co-moderator for the session where Bhat presented the data. Bhat did not report a study funding source. Bhat and Gao reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

BOSTON — The sooner that patients with acute pulmonary embolism (PE) get treated with mechanical thrombectomy, the greater the likelihood that they will have favorable short- and long-term outcomes, regardless of their degree of initial risk, a study of registry data showed.

Among nearly 800 patients with acute PE whose data are recorded in the FlowTriever All-Comer Registry for Patient Safety and Hemodynamics (FLASH), a prospective multicenter registry of individuals treated with mechanical thrombectomy using the FlowTriever system (Inari Medical), shorter time from admission to mechanical thrombectomy was associated with significantly greater reductions in intraprocedural mean and systolic pulmonary artery pressures (PAP), greater reductions in the right ventricular/left ventricular (RV/LV) ratio, and longer 6-minute walk times at 6 months, reported Krunal H. Patel, MD, a pulmonary and critical care fellow at the Lewis Katz School of Medicine at Temple University Hospital in Philadelphia.

“Mechanical thrombectomy in the FLASH registry showed a mortality benefit. I think as time progresses and mechanical thrombectomy becomes more popular, we’re just going to need to figure out what is the ideal time for intervention,” he said during an oral abstract session at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.

“There’s mortality benefit in any case whether the patient is high-risk or intermediate-high. This is a thought-provoking retrospective analysis that says that early intervention is probably better than doing it late, but regardless, the FLASH registry trial showed that early thrombectomy or thrombectomy in general shows positive mortality benefit,” Patel said in an interview.

He likened the challenge for pulmonary and critical care specialists to that of interventional cardiologists, who have determined that the ideal window for starting percutaneous coronary interventions is within 90 minutes of the patient’s arrival at the facility.

“I think we have to get our ‘door-to-balloon’ time for PE care,” he said.
 

Study Details

Patel and colleague Parth M. Rali, MD, FCCP, associate professor of thoracic medicine at Temple, conducted a retrospective review of data on 787 US patients in the FLASH registry for whom time to mechanical thrombectomy data were available. They stratified the patients into short and long time to mechanical thrombectomy groups, with “short” defined as ≤ 12 hours of presentation and “long” as > 12 hours.

They found that the median time to thrombectomy was 19.68 hours. In all, 242 patients (31%) were treated within the short window, and the remaining 545 patients (69%) were treated after at least 12 hours had passed.

Comparing clinical characteristics between the groups, the investigators noted that significantly more patients in the short time group vs long time group were categorized as high-risk (11.2% vs 6.2%; P = .0026). This difference is likely due to the need for greater urgency among high-risk patients, Patel said.

Patients in the short time group also had significantly higher baseline RV/LV ratios and lactate levels, but baseline dyspnea scores and pre-procedure median and systolic PAP were similar between the groups.

The mean time to thrombectomy was 6.08 hours in the short time group vs 34.04 hours in the long time group. Their respective median times were 6.01 and 24.73 hours.

The procedural time was similar between the groups, at 45 and 42 minutes, respectively.

The location of the treated thrombus was central only in 35.1% and 26.5% patients in the short and long time groups, respectively. Lobar-only thrombi were treated in 7.9% and 14.3%, respectively, and both central and lobar thrombi were treated in 57.0% and 59.2%, respectively.

Both 48-hour and 30-day all-cause mortality rates were similar between the groups (0.4%/0.2% and 0.5%/1.0%).

Patients in the short time group had slightly but significantly longer post-procedure hospital and intensive care unit stays, but 30-day readmission rates — whether for PE- or non-PE–related causes — were similar.

Where the differences between the groups really showed, however, were PAP reductions over baseline, with decline in median pressures of −8.7 mm Hg in the short group vs −7.2 mm Hg in the long group (P = .0008), and drops in systolic PAP of −14.4 vs −12.1 mm Hg, respectively (P = .0011).

In addition, reductions in RV/LV ratios from baseline were also significantly greater among patients whose thrombectomies had been expedited at the 48-hour, 30-day, and 6-month follow-up periods.

At 6 months, patients who had received mechanical thrombectomy within 12 hours also had significantly longer 6-minute walk distances (442.2 vs 390.5 m; P = .0032).
 

Low Thrombolysis Rate

Following his presentation, session co-moderator Galina Glazman-Kuczaj, MD, from the Division of Pulmonary and Critical Care Medicine at Albany Med Health System, Albany, New York, asked Patel what percentage of patients, if any, had received thrombolytic therapy before the thrombectomy procedure.

He noted that only 1% or 2% patients in the FLASH registry received thrombolysis.

In an interview, Glazman-Kuczaj said that “it was reassuring for [Patel] to report that it was only a small population of patients who got thrombolysis beforehand in either group because you would expect that maybe people in the group that took longer to have a thrombectomy got some thrombolysis beforehand and that perhaps they were more stable, but it seems like thrombectomy was the first-line treatment in both groups.”

The FLASH Registry is funded by Inari Medical. Patel and Glazman-Kuczaj reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

BOSTON — The sooner that patients with acute pulmonary embolism (PE) get treated with mechanical thrombectomy, the greater the likelihood that they will have favorable short- and long-term outcomes, regardless of their degree of initial risk, a study of registry data showed.

Among nearly 800 patients with acute PE whose data are recorded in the FlowTriever All-Comer Registry for Patient Safety and Hemodynamics (FLASH), a prospective multicenter registry of individuals treated with mechanical thrombectomy using the FlowTriever system (Inari Medical), shorter time from admission to mechanical thrombectomy was associated with significantly greater reductions in intraprocedural mean and systolic pulmonary artery pressures (PAP), greater reductions in the right ventricular/left ventricular (RV/LV) ratio, and longer 6-minute walk times at 6 months, reported Krunal H. Patel, MD, a pulmonary and critical care fellow at the Lewis Katz School of Medicine at Temple University Hospital in Philadelphia.

“Mechanical thrombectomy in the FLASH registry showed a mortality benefit. I think as time progresses and mechanical thrombectomy becomes more popular, we’re just going to need to figure out what is the ideal time for intervention,” he said during an oral abstract session at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.

“There’s mortality benefit in any case whether the patient is high-risk or intermediate-high. This is a thought-provoking retrospective analysis that says that early intervention is probably better than doing it late, but regardless, the FLASH registry trial showed that early thrombectomy or thrombectomy in general shows positive mortality benefit,” Patel said in an interview.

He likened the challenge for pulmonary and critical care specialists to that of interventional cardiologists, who have determined that the ideal window for starting percutaneous coronary interventions is within 90 minutes of the patient’s arrival at the facility.

“I think we have to get our ‘door-to-balloon’ time for PE care,” he said.
 

Study Details

Patel and colleague Parth M. Rali, MD, FCCP, associate professor of thoracic medicine at Temple, conducted a retrospective review of data on 787 US patients in the FLASH registry for whom time to mechanical thrombectomy data were available. They stratified the patients into short and long time to mechanical thrombectomy groups, with “short” defined as ≤ 12 hours of presentation and “long” as > 12 hours.

They found that the median time to thrombectomy was 19.68 hours. In all, 242 patients (31%) were treated within the short window, and the remaining 545 patients (69%) were treated after at least 12 hours had passed.

Comparing clinical characteristics between the groups, the investigators noted that significantly more patients in the short time group vs long time group were categorized as high-risk (11.2% vs 6.2%; P = .0026). This difference is likely due to the need for greater urgency among high-risk patients, Patel said.

Patients in the short time group also had significantly higher baseline RV/LV ratios and lactate levels, but baseline dyspnea scores and pre-procedure median and systolic PAP were similar between the groups.

The mean time to thrombectomy was 6.08 hours in the short time group vs 34.04 hours in the long time group. Their respective median times were 6.01 and 24.73 hours.

The procedural time was similar between the groups, at 45 and 42 minutes, respectively.

The location of the treated thrombus was central only in 35.1% and 26.5% patients in the short and long time groups, respectively. Lobar-only thrombi were treated in 7.9% and 14.3%, respectively, and both central and lobar thrombi were treated in 57.0% and 59.2%, respectively.

Both 48-hour and 30-day all-cause mortality rates were similar between the groups (0.4%/0.2% and 0.5%/1.0%).

Patients in the short time group had slightly but significantly longer post-procedure hospital and intensive care unit stays, but 30-day readmission rates — whether for PE- or non-PE–related causes — were similar.

Where the differences between the groups really showed, however, were PAP reductions over baseline, with decline in median pressures of −8.7 mm Hg in the short group vs −7.2 mm Hg in the long group (P = .0008), and drops in systolic PAP of −14.4 vs −12.1 mm Hg, respectively (P = .0011).

In addition, reductions in RV/LV ratios from baseline were also significantly greater among patients whose thrombectomies had been expedited at the 48-hour, 30-day, and 6-month follow-up periods.

At 6 months, patients who had received mechanical thrombectomy within 12 hours also had significantly longer 6-minute walk distances (442.2 vs 390.5 m; P = .0032).
 

Low Thrombolysis Rate

Following his presentation, session co-moderator Galina Glazman-Kuczaj, MD, from the Division of Pulmonary and Critical Care Medicine at Albany Med Health System, Albany, New York, asked Patel what percentage of patients, if any, had received thrombolytic therapy before the thrombectomy procedure.

He noted that only 1% or 2% patients in the FLASH registry received thrombolysis.

In an interview, Glazman-Kuczaj said that “it was reassuring for [Patel] to report that it was only a small population of patients who got thrombolysis beforehand in either group because you would expect that maybe people in the group that took longer to have a thrombectomy got some thrombolysis beforehand and that perhaps they were more stable, but it seems like thrombectomy was the first-line treatment in both groups.”

The FLASH Registry is funded by Inari Medical. Patel and Glazman-Kuczaj reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

BOSTON — The sooner that patients with acute pulmonary embolism (PE) get treated with mechanical thrombectomy, the greater the likelihood that they will have favorable short- and long-term outcomes, regardless of their degree of initial risk, a study of registry data showed.

Among nearly 800 patients with acute PE whose data are recorded in the FlowTriever All-Comer Registry for Patient Safety and Hemodynamics (FLASH), a prospective multicenter registry of individuals treated with mechanical thrombectomy using the FlowTriever system (Inari Medical), shorter time from admission to mechanical thrombectomy was associated with significantly greater reductions in intraprocedural mean and systolic pulmonary artery pressures (PAP), greater reductions in the right ventricular/left ventricular (RV/LV) ratio, and longer 6-minute walk times at 6 months, reported Krunal H. Patel, MD, a pulmonary and critical care fellow at the Lewis Katz School of Medicine at Temple University Hospital in Philadelphia.

“Mechanical thrombectomy in the FLASH registry showed a mortality benefit. I think as time progresses and mechanical thrombectomy becomes more popular, we’re just going to need to figure out what is the ideal time for intervention,” he said during an oral abstract session at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.

“There’s mortality benefit in any case whether the patient is high-risk or intermediate-high. This is a thought-provoking retrospective analysis that says that early intervention is probably better than doing it late, but regardless, the FLASH registry trial showed that early thrombectomy or thrombectomy in general shows positive mortality benefit,” Patel said in an interview.

He likened the challenge for pulmonary and critical care specialists to that of interventional cardiologists, who have determined that the ideal window for starting percutaneous coronary interventions is within 90 minutes of the patient’s arrival at the facility.

“I think we have to get our ‘door-to-balloon’ time for PE care,” he said.
 

Study Details

Patel and colleague Parth M. Rali, MD, FCCP, associate professor of thoracic medicine at Temple, conducted a retrospective review of data on 787 US patients in the FLASH registry for whom time to mechanical thrombectomy data were available. They stratified the patients into short and long time to mechanical thrombectomy groups, with “short” defined as ≤ 12 hours of presentation and “long” as > 12 hours.

They found that the median time to thrombectomy was 19.68 hours. In all, 242 patients (31%) were treated within the short window, and the remaining 545 patients (69%) were treated after at least 12 hours had passed.

Comparing clinical characteristics between the groups, the investigators noted that significantly more patients in the short time group vs long time group were categorized as high-risk (11.2% vs 6.2%; P = .0026). This difference is likely due to the need for greater urgency among high-risk patients, Patel said.

Patients in the short time group also had significantly higher baseline RV/LV ratios and lactate levels, but baseline dyspnea scores and pre-procedure median and systolic PAP were similar between the groups.

The mean time to thrombectomy was 6.08 hours in the short time group vs 34.04 hours in the long time group. Their respective median times were 6.01 and 24.73 hours.

The procedural time was similar between the groups, at 45 and 42 minutes, respectively.

The location of the treated thrombus was central only in 35.1% and 26.5% patients in the short and long time groups, respectively. Lobar-only thrombi were treated in 7.9% and 14.3%, respectively, and both central and lobar thrombi were treated in 57.0% and 59.2%, respectively.

Both 48-hour and 30-day all-cause mortality rates were similar between the groups (0.4%/0.2% and 0.5%/1.0%).

Patients in the short time group had slightly but significantly longer post-procedure hospital and intensive care unit stays, but 30-day readmission rates — whether for PE- or non-PE–related causes — were similar.

Where the differences between the groups really showed, however, were PAP reductions over baseline, with decline in median pressures of −8.7 mm Hg in the short group vs −7.2 mm Hg in the long group (P = .0008), and drops in systolic PAP of −14.4 vs −12.1 mm Hg, respectively (P = .0011).

In addition, reductions in RV/LV ratios from baseline were also significantly greater among patients whose thrombectomies had been expedited at the 48-hour, 30-day, and 6-month follow-up periods.

At 6 months, patients who had received mechanical thrombectomy within 12 hours also had significantly longer 6-minute walk distances (442.2 vs 390.5 m; P = .0032).
 

Low Thrombolysis Rate

Following his presentation, session co-moderator Galina Glazman-Kuczaj, MD, from the Division of Pulmonary and Critical Care Medicine at Albany Med Health System, Albany, New York, asked Patel what percentage of patients, if any, had received thrombolytic therapy before the thrombectomy procedure.

He noted that only 1% or 2% patients in the FLASH registry received thrombolysis.

In an interview, Glazman-Kuczaj said that “it was reassuring for [Patel] to report that it was only a small population of patients who got thrombolysis beforehand in either group because you would expect that maybe people in the group that took longer to have a thrombectomy got some thrombolysis beforehand and that perhaps they were more stable, but it seems like thrombectomy was the first-line treatment in both groups.”

The FLASH Registry is funded by Inari Medical. Patel and Glazman-Kuczaj reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

A quadruplet induction regimen of isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in the treatment of newly diagnosed multiple myeloma (MM) shows a notably high response, with a favorable safety profile, according to the first findings of the ongoing, novel MIDAS trial.

“We found that this induction induced exceptionally high response and minimal residual disease (MRD) negativity rates,” said first author Aurore Perrot, MD, PhD, an associate professor of hematology at the University of Toulouse in France, in presenting the findings at the annual meeting of the International Myeloma Society (IMS).

“These rates are the highest reported to date regarding MRD negativity,” she said.

The results from a first interim analysis offer encouraging groundwork in the trial that is investigating the tailoring of subsequent therapeutic choices in patients with newly diagnosed MM based on MRD status after six cycles of induction therapy.

In the standard treatment regimen of induction therapy followed by up-front autologous stem cell transplant (ASCT), the use of ever-improving quadruplet regimens is bolstering prognoses, while the role of up-front ASCT continues to be debated, Perrot explained. She noted that no prospective trials have compared up-front transplant vs no transplant following a quadruplet regimen.

In reporting on the initial findings from the induction phase of the phase 3 IFM 2020-02 MIDAS study, Perrot described results among 791 transplant-eligible patients with newly diagnosed MM and a median age of 59 who were enrolled at 72 centers between December 2021 and July 2023.

The patients were treated with six cycles of 28 days of the Isa-KRd regimen, consisting of isatuximab 10 mg/kg (weekly for 4 weeks then biweekly), carfilzomib 20 mg/m2 on day 1 cycle 1, then 56 mg/m² (days 1, 8, and 15), lenalidomide 25 mg/d (from day 1 to day 21), and dexamethasone at 40 mg/wk.

Overall, MM was classified as International Staging System (ISS) III in 120 patients (15%) and revised-ISS III in 76 (10%) patients.

Of 757 patients undergoing cytogenetics, 8% were considered high risk on the basis of a linear predictor score > 1, while the t(11;14) translocation, a chromosomal abnormality, was present in 26% of patients.

Extramedullary disease was present in five patients, while 53 (7%) had circulating plasma cells.

All 791 patients initiated Isa-KRd induction, and most (766, 97%) had at least one peripheral stem cell mobilization course, with 761 having at least one apheresis. The median number of CD34+ cells collected was 7.106/kg.

The peripheral stem cells collected allowed for potential tandem transplants in 719 patients. In total, 757 patients completed six cycles of Isa-KRd, with an overall response rate of 95%.

In the intent-to-treat (ITT) population, a very good partial response or better was achieved in 92% of patients following induction, with a rate of 99% in the per-protocol [PP] population.

Of 751 patients in the post-induction ITT population, the MRD negativity rates were 63% at the threshold of 10⁻⁵ and 47% at the threshold of 10⁻⁶, with corresponding rates of 66% and 50%, respectively, in the PP population.

The rates of near-complete response and complete response were 64% and 66% in the ITT population, and 69% and 71% in the PP population.

Of note, no significant differences were observed in prognostic subgroups, with a trend for a higher MRD negative rate among poorer prognostic groups, Perrot said.

However, notable variability was observed in terms of MRD negativity at 10⁻⁵ after induction among some cytogenic groups, with an MRD negativity rate as high as 81% among patients with the t(4;14) translocation vs 62% among those without the abnormality (P = .002), while it was only 40% among patients with the t(11;14) translocation vs 64% without (P < .0001).

“This is the first time we have observed this correlation between the MRD negativity and these cytogenetic subgroups,” Perrot noted.

“For the moment, we are not saying that patients with the t(11;14) translocation have a poor prognosis,” she added. “But just that the early assessment of MRD shows the lower negativity rates.”
 

Safety

Seven patients experienced disease progression and five died during induction, with one dying from disease progression, two deaths related to cardiac adverse events (AEs), and two related to other AEs.

In terms of safety, the most common grade 3-4 AEs were neutropenia (25%), thrombocytopenia (5%), and infections (7%).

Peripheral neuropathy was reported among 13% of patients at any grade, and less than 1% grade 3-4.

“Our findings confirm that six cycles of Isa-KRd induce exceptionally high response and MRD negativity rates, not only at a sensitivity of 10⁻⁵ but also at 10⁻⁶,” Perrot said.

She noted that, in comparison, the MRD negativity rate at 10−5 in the related CASSIOPEIA, GRIFFIN, and IsKia trials were 35%, 22%, and 45%, respectively.

“A longer follow-up is needed to better interpret the significance of achieving MRD negativity in patients with different cytogenetic abnormalities,” Perrot added.

“Importantly, the Isa-KRd induction ensures successful stem cell collection, with no new safety signals,” she said.

The Isa-KRd regimen is not yet approved, hence only used in clinical trials, but Perrot told this publication the current evidence should help change that.

“The IsKia trial is comparing KRd and Isa-KRd, and Sanofi should try to approve the combo,” she said. “We hope the Midas data will support this approval.”
 

Questions Aplenty Moving Ahead

While the results are just the first from the ongoing trial, interest in the study and its design is high, Joseph Mikhael, MD, chief medical officer of the International Myeloma Foundation, told this publication.

“To have a large trial algorithm that is based on response and in particular MRD is novel and reflects the power of MRD in myeloma,” said Mikhael, a professor of applied cancer research and drug discovery at the Translational Genomics Research Institute, City of Hope Cancer Center, Phoenix, Arizona.

“Although the results are preliminary, these kinds of trials can inform our approach to MRD testing and may result in more personalized and effective treatments for patients,” he said. “This may include the potential to de-escalate or even stop therapies that have historically been given for longer or provide more intense therapies for patients with inadequate response.”

“We know the biology of myeloma is ‘one size fits all’, so the design of our trials should reflect that heterogeneity.”

Further commenting on the research, the meeting discussant Sagar Lonial, MD, professor and chair of the Department of Hematology and Medical Oncology and the Anne and Bernard Gray Professor in Cancer at the Winship Cancer Institute of Emory University, Atlanta, Georgia, offered cautious optimism.

Referencing the tale of Midas in Greek mythology as having a “be careful what you wish for” lesson, Lonial pondered that, likewise, a question that may be considered regarding MRD is “whether this is in fact a gift — or could this be a curse that’s going to get us into trouble at some point down the road. I don’t know the answer.”

Some cautionary lessons include prior research indicating that patients with high-risk disease may achieve a complete remission early — but they lose remission earlier down the road, he noted.

Other considerations as the research moves forward: “Recognizing that MRD may in fact be more important than genetics — which is a premise of the current trial,” Lonial pondered. “Does MRD override genetics, or do they travel together?”

The study is ongoing, with future results expected in terms of ASCT vs no ASCT for patients with high and low risk, as well as single vs tandem ASCT.

The trial received financial support from Amgen, Bristol-Myers Squibb, and Sanofi. Perrot reported ties with Amgen, Bristol Myers Squibb, and Sanofi. Mikhael disclosed ties with Amgen, Bristol Myers Squibb, and Sanofi. Lonial reported relationships with Celgene, Bristol-Myers Squibb, Amgen, and Sanofi.

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

A quadruplet induction regimen of isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in the treatment of newly diagnosed multiple myeloma (MM) shows a notably high response, with a favorable safety profile, according to the first findings of the ongoing, novel MIDAS trial.

“We found that this induction induced exceptionally high response and minimal residual disease (MRD) negativity rates,” said first author Aurore Perrot, MD, PhD, an associate professor of hematology at the University of Toulouse in France, in presenting the findings at the annual meeting of the International Myeloma Society (IMS).

“These rates are the highest reported to date regarding MRD negativity,” she said.

The results from a first interim analysis offer encouraging groundwork in the trial that is investigating the tailoring of subsequent therapeutic choices in patients with newly diagnosed MM based on MRD status after six cycles of induction therapy.

In the standard treatment regimen of induction therapy followed by up-front autologous stem cell transplant (ASCT), the use of ever-improving quadruplet regimens is bolstering prognoses, while the role of up-front ASCT continues to be debated, Perrot explained. She noted that no prospective trials have compared up-front transplant vs no transplant following a quadruplet regimen.

In reporting on the initial findings from the induction phase of the phase 3 IFM 2020-02 MIDAS study, Perrot described results among 791 transplant-eligible patients with newly diagnosed MM and a median age of 59 who were enrolled at 72 centers between December 2021 and July 2023.

The patients were treated with six cycles of 28 days of the Isa-KRd regimen, consisting of isatuximab 10 mg/kg (weekly for 4 weeks then biweekly), carfilzomib 20 mg/m2 on day 1 cycle 1, then 56 mg/m² (days 1, 8, and 15), lenalidomide 25 mg/d (from day 1 to day 21), and dexamethasone at 40 mg/wk.

Overall, MM was classified as International Staging System (ISS) III in 120 patients (15%) and revised-ISS III in 76 (10%) patients.

Of 757 patients undergoing cytogenetics, 8% were considered high risk on the basis of a linear predictor score > 1, while the t(11;14) translocation, a chromosomal abnormality, was present in 26% of patients.

Extramedullary disease was present in five patients, while 53 (7%) had circulating plasma cells.

All 791 patients initiated Isa-KRd induction, and most (766, 97%) had at least one peripheral stem cell mobilization course, with 761 having at least one apheresis. The median number of CD34+ cells collected was 7.106/kg.

The peripheral stem cells collected allowed for potential tandem transplants in 719 patients. In total, 757 patients completed six cycles of Isa-KRd, with an overall response rate of 95%.

In the intent-to-treat (ITT) population, a very good partial response or better was achieved in 92% of patients following induction, with a rate of 99% in the per-protocol [PP] population.

Of 751 patients in the post-induction ITT population, the MRD negativity rates were 63% at the threshold of 10⁻⁵ and 47% at the threshold of 10⁻⁶, with corresponding rates of 66% and 50%, respectively, in the PP population.

The rates of near-complete response and complete response were 64% and 66% in the ITT population, and 69% and 71% in the PP population.

Of note, no significant differences were observed in prognostic subgroups, with a trend for a higher MRD negative rate among poorer prognostic groups, Perrot said.

However, notable variability was observed in terms of MRD negativity at 10⁻⁵ after induction among some cytogenic groups, with an MRD negativity rate as high as 81% among patients with the t(4;14) translocation vs 62% among those without the abnormality (P = .002), while it was only 40% among patients with the t(11;14) translocation vs 64% without (P < .0001).

“This is the first time we have observed this correlation between the MRD negativity and these cytogenetic subgroups,” Perrot noted.

“For the moment, we are not saying that patients with the t(11;14) translocation have a poor prognosis,” she added. “But just that the early assessment of MRD shows the lower negativity rates.”
 

Safety

Seven patients experienced disease progression and five died during induction, with one dying from disease progression, two deaths related to cardiac adverse events (AEs), and two related to other AEs.

In terms of safety, the most common grade 3-4 AEs were neutropenia (25%), thrombocytopenia (5%), and infections (7%).

Peripheral neuropathy was reported among 13% of patients at any grade, and less than 1% grade 3-4.

“Our findings confirm that six cycles of Isa-KRd induce exceptionally high response and MRD negativity rates, not only at a sensitivity of 10⁻⁵ but also at 10⁻⁶,” Perrot said.

She noted that, in comparison, the MRD negativity rate at 10−5 in the related CASSIOPEIA, GRIFFIN, and IsKia trials were 35%, 22%, and 45%, respectively.

“A longer follow-up is needed to better interpret the significance of achieving MRD negativity in patients with different cytogenetic abnormalities,” Perrot added.

“Importantly, the Isa-KRd induction ensures successful stem cell collection, with no new safety signals,” she said.

The Isa-KRd regimen is not yet approved, hence only used in clinical trials, but Perrot told this publication the current evidence should help change that.

“The IsKia trial is comparing KRd and Isa-KRd, and Sanofi should try to approve the combo,” she said. “We hope the Midas data will support this approval.”
 

Questions Aplenty Moving Ahead

While the results are just the first from the ongoing trial, interest in the study and its design is high, Joseph Mikhael, MD, chief medical officer of the International Myeloma Foundation, told this publication.

“To have a large trial algorithm that is based on response and in particular MRD is novel and reflects the power of MRD in myeloma,” said Mikhael, a professor of applied cancer research and drug discovery at the Translational Genomics Research Institute, City of Hope Cancer Center, Phoenix, Arizona.

“Although the results are preliminary, these kinds of trials can inform our approach to MRD testing and may result in more personalized and effective treatments for patients,” he said. “This may include the potential to de-escalate or even stop therapies that have historically been given for longer or provide more intense therapies for patients with inadequate response.”

“We know the biology of myeloma is ‘one size fits all’, so the design of our trials should reflect that heterogeneity.”

Further commenting on the research, the meeting discussant Sagar Lonial, MD, professor and chair of the Department of Hematology and Medical Oncology and the Anne and Bernard Gray Professor in Cancer at the Winship Cancer Institute of Emory University, Atlanta, Georgia, offered cautious optimism.

Referencing the tale of Midas in Greek mythology as having a “be careful what you wish for” lesson, Lonial pondered that, likewise, a question that may be considered regarding MRD is “whether this is in fact a gift — or could this be a curse that’s going to get us into trouble at some point down the road. I don’t know the answer.”

Some cautionary lessons include prior research indicating that patients with high-risk disease may achieve a complete remission early — but they lose remission earlier down the road, he noted.

Other considerations as the research moves forward: “Recognizing that MRD may in fact be more important than genetics — which is a premise of the current trial,” Lonial pondered. “Does MRD override genetics, or do they travel together?”

The study is ongoing, with future results expected in terms of ASCT vs no ASCT for patients with high and low risk, as well as single vs tandem ASCT.

The trial received financial support from Amgen, Bristol-Myers Squibb, and Sanofi. Perrot reported ties with Amgen, Bristol Myers Squibb, and Sanofi. Mikhael disclosed ties with Amgen, Bristol Myers Squibb, and Sanofi. Lonial reported relationships with Celgene, Bristol-Myers Squibb, Amgen, and Sanofi.

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

A quadruplet induction regimen of isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in the treatment of newly diagnosed multiple myeloma (MM) shows a notably high response, with a favorable safety profile, according to the first findings of the ongoing, novel MIDAS trial.

“We found that this induction induced exceptionally high response and minimal residual disease (MRD) negativity rates,” said first author Aurore Perrot, MD, PhD, an associate professor of hematology at the University of Toulouse in France, in presenting the findings at the annual meeting of the International Myeloma Society (IMS).

“These rates are the highest reported to date regarding MRD negativity,” she said.

The results from a first interim analysis offer encouraging groundwork in the trial that is investigating the tailoring of subsequent therapeutic choices in patients with newly diagnosed MM based on MRD status after six cycles of induction therapy.

In the standard treatment regimen of induction therapy followed by up-front autologous stem cell transplant (ASCT), the use of ever-improving quadruplet regimens is bolstering prognoses, while the role of up-front ASCT continues to be debated, Perrot explained. She noted that no prospective trials have compared up-front transplant vs no transplant following a quadruplet regimen.

In reporting on the initial findings from the induction phase of the phase 3 IFM 2020-02 MIDAS study, Perrot described results among 791 transplant-eligible patients with newly diagnosed MM and a median age of 59 who were enrolled at 72 centers between December 2021 and July 2023.

The patients were treated with six cycles of 28 days of the Isa-KRd regimen, consisting of isatuximab 10 mg/kg (weekly for 4 weeks then biweekly), carfilzomib 20 mg/m2 on day 1 cycle 1, then 56 mg/m² (days 1, 8, and 15), lenalidomide 25 mg/d (from day 1 to day 21), and dexamethasone at 40 mg/wk.

Overall, MM was classified as International Staging System (ISS) III in 120 patients (15%) and revised-ISS III in 76 (10%) patients.

Of 757 patients undergoing cytogenetics, 8% were considered high risk on the basis of a linear predictor score > 1, while the t(11;14) translocation, a chromosomal abnormality, was present in 26% of patients.

Extramedullary disease was present in five patients, while 53 (7%) had circulating plasma cells.

All 791 patients initiated Isa-KRd induction, and most (766, 97%) had at least one peripheral stem cell mobilization course, with 761 having at least one apheresis. The median number of CD34+ cells collected was 7.106/kg.

The peripheral stem cells collected allowed for potential tandem transplants in 719 patients. In total, 757 patients completed six cycles of Isa-KRd, with an overall response rate of 95%.

In the intent-to-treat (ITT) population, a very good partial response or better was achieved in 92% of patients following induction, with a rate of 99% in the per-protocol [PP] population.

Of 751 patients in the post-induction ITT population, the MRD negativity rates were 63% at the threshold of 10⁻⁵ and 47% at the threshold of 10⁻⁶, with corresponding rates of 66% and 50%, respectively, in the PP population.

The rates of near-complete response and complete response were 64% and 66% in the ITT population, and 69% and 71% in the PP population.

Of note, no significant differences were observed in prognostic subgroups, with a trend for a higher MRD negative rate among poorer prognostic groups, Perrot said.

However, notable variability was observed in terms of MRD negativity at 10⁻⁵ after induction among some cytogenic groups, with an MRD negativity rate as high as 81% among patients with the t(4;14) translocation vs 62% among those without the abnormality (P = .002), while it was only 40% among patients with the t(11;14) translocation vs 64% without (P < .0001).

“This is the first time we have observed this correlation between the MRD negativity and these cytogenetic subgroups,” Perrot noted.

“For the moment, we are not saying that patients with the t(11;14) translocation have a poor prognosis,” she added. “But just that the early assessment of MRD shows the lower negativity rates.”
 

Safety

Seven patients experienced disease progression and five died during induction, with one dying from disease progression, two deaths related to cardiac adverse events (AEs), and two related to other AEs.

In terms of safety, the most common grade 3-4 AEs were neutropenia (25%), thrombocytopenia (5%), and infections (7%).

Peripheral neuropathy was reported among 13% of patients at any grade, and less than 1% grade 3-4.

“Our findings confirm that six cycles of Isa-KRd induce exceptionally high response and MRD negativity rates, not only at a sensitivity of 10⁻⁵ but also at 10⁻⁶,” Perrot said.

She noted that, in comparison, the MRD negativity rate at 10−5 in the related CASSIOPEIA, GRIFFIN, and IsKia trials were 35%, 22%, and 45%, respectively.

“A longer follow-up is needed to better interpret the significance of achieving MRD negativity in patients with different cytogenetic abnormalities,” Perrot added.

“Importantly, the Isa-KRd induction ensures successful stem cell collection, with no new safety signals,” she said.

The Isa-KRd regimen is not yet approved, hence only used in clinical trials, but Perrot told this publication the current evidence should help change that.

“The IsKia trial is comparing KRd and Isa-KRd, and Sanofi should try to approve the combo,” she said. “We hope the Midas data will support this approval.”
 

Questions Aplenty Moving Ahead

While the results are just the first from the ongoing trial, interest in the study and its design is high, Joseph Mikhael, MD, chief medical officer of the International Myeloma Foundation, told this publication.

“To have a large trial algorithm that is based on response and in particular MRD is novel and reflects the power of MRD in myeloma,” said Mikhael, a professor of applied cancer research and drug discovery at the Translational Genomics Research Institute, City of Hope Cancer Center, Phoenix, Arizona.

“Although the results are preliminary, these kinds of trials can inform our approach to MRD testing and may result in more personalized and effective treatments for patients,” he said. “This may include the potential to de-escalate or even stop therapies that have historically been given for longer or provide more intense therapies for patients with inadequate response.”

“We know the biology of myeloma is ‘one size fits all’, so the design of our trials should reflect that heterogeneity.”

Further commenting on the research, the meeting discussant Sagar Lonial, MD, professor and chair of the Department of Hematology and Medical Oncology and the Anne and Bernard Gray Professor in Cancer at the Winship Cancer Institute of Emory University, Atlanta, Georgia, offered cautious optimism.

Referencing the tale of Midas in Greek mythology as having a “be careful what you wish for” lesson, Lonial pondered that, likewise, a question that may be considered regarding MRD is “whether this is in fact a gift — or could this be a curse that’s going to get us into trouble at some point down the road. I don’t know the answer.”

Some cautionary lessons include prior research indicating that patients with high-risk disease may achieve a complete remission early — but they lose remission earlier down the road, he noted.

Other considerations as the research moves forward: “Recognizing that MRD may in fact be more important than genetics — which is a premise of the current trial,” Lonial pondered. “Does MRD override genetics, or do they travel together?”

The study is ongoing, with future results expected in terms of ASCT vs no ASCT for patients with high and low risk, as well as single vs tandem ASCT.

The trial received financial support from Amgen, Bristol-Myers Squibb, and Sanofi. Perrot reported ties with Amgen, Bristol Myers Squibb, and Sanofi. Mikhael disclosed ties with Amgen, Bristol Myers Squibb, and Sanofi. Lonial reported relationships with Celgene, Bristol-Myers Squibb, Amgen, and Sanofi.

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

BOSTON — Patients with pulmonary embolism (PE) who also present with interstitial lung disease (ILD) have worse outcomes with respect to in-hospital mortality, length of hospital stay, hospital cost, and all-cause readmission, according to results from a new retrospective analysis.

“There’s a lot of evidence now that demonstrates that ILD, in general, leads to worse mortality, morbidity in hospital complications, and overall [outcomes]. It’s not hard to extrapolate this to pulmonary embolism outcomes, too. Unfortunately, there’s not a whole lot of evidence out there to really demonstrate it,” Leah Yuan, MD, said during a presentation of the results at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.

The question is complicated by the nebulous nature of ILD, which includes a diverse set of diseases and etiologies, and different levels of inflammation and fibrosis. It has been employed in the Pulmonary Embolism Severity Index but counts for only 10 points out of 210. “If you look at ILD and PE outcomes, there’s nothing really out there [in the literature],” Yuan said in an interview. She is a resident physician at Cook County Health and Hospitals System.

The new study suggested that ILD could have an important influence and perhaps should have greater weight in risk stratification of patients with PE, she said. “We looked at all-cause readmissions and we looked at in-hospital mortality, [both] of which are significant for increased odds ratio. One thing that I’m very curious to see is whether there is increased PE readmissions [associated with ILD], which is something that we couldn’t find to be significant in our study,” said Yuan.

The researchers used data from hospitalizations for PE drawn from the Nationwide Readmissions Database in 2019, using International Classification of Diseases, Tenth Revision, codes to identify admissions. Among a total of 105,133 patients admitted for PE, 158 patients also had ILD. The mean age was 63.6 years for those without ILD (SD, 0.1) and 66.5 years for those with ILD (SD, 1.3).

Admission with ILD was associated with all-cause readmission (odds ratio [OR], 4.12; P < .01), in-hospital mortality (OR, 2.17; P = .01), a longer length of stay (+2.07 days; P < .01), and higher hospitalization charges (+$22,627; P < .01).

In the Q&A period after the presentation, Parth Rali, MD, professor of thoracic medicine and surgery at Temple University, Philadelphia, suggested phenotyping patients to better understand the location of the PE in relation to the ILD. “It may not fall into your classic PE classification. It may just depend on where the clot is in relationship to the interstitial lung disease. I think that’s where the field is going to evolve,” he later said in an interview.

“What is interesting is that patients with interstitial lung disease have a lot of fibrotic disease, and they do not need to have a large clot burden to make them sick. An example [is someone] who has undergone a lung transplant evaluation, and if their right lung is completely diseased from interstitial lung disease and if they get a big blood clot on the right side, it doesn’t affect them because the lung is already fibrotic, so the clot doesn’t matter. If they get a small clot [in the left lung], even though if you look at the standard PE classification they may qualify as a low-risk PE or even as an intermediate-low-risk PE, they are much sicker because that’s the functioning part of the lung,” said Rali.

He advised physicians to pay close attention to the location of PEs in relation to fibrotic tissue in patients with ILD. A PE in healthy lung tissue could have an outsized effect on hemodynamics, whereas a PE in fibrotic tissue may be clinically insignificant and not require treatment. “So it goes both ways: You don’t overtreat and you don’t undertreat,” Rali said.

Yuan and Rali disclosed no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

BOSTON — Patients with pulmonary embolism (PE) who also present with interstitial lung disease (ILD) have worse outcomes with respect to in-hospital mortality, length of hospital stay, hospital cost, and all-cause readmission, according to results from a new retrospective analysis.

“There’s a lot of evidence now that demonstrates that ILD, in general, leads to worse mortality, morbidity in hospital complications, and overall [outcomes]. It’s not hard to extrapolate this to pulmonary embolism outcomes, too. Unfortunately, there’s not a whole lot of evidence out there to really demonstrate it,” Leah Yuan, MD, said during a presentation of the results at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.

The question is complicated by the nebulous nature of ILD, which includes a diverse set of diseases and etiologies, and different levels of inflammation and fibrosis. It has been employed in the Pulmonary Embolism Severity Index but counts for only 10 points out of 210. “If you look at ILD and PE outcomes, there’s nothing really out there [in the literature],” Yuan said in an interview. She is a resident physician at Cook County Health and Hospitals System.

The new study suggested that ILD could have an important influence and perhaps should have greater weight in risk stratification of patients with PE, she said. “We looked at all-cause readmissions and we looked at in-hospital mortality, [both] of which are significant for increased odds ratio. One thing that I’m very curious to see is whether there is increased PE readmissions [associated with ILD], which is something that we couldn’t find to be significant in our study,” said Yuan.

The researchers used data from hospitalizations for PE drawn from the Nationwide Readmissions Database in 2019, using International Classification of Diseases, Tenth Revision, codes to identify admissions. Among a total of 105,133 patients admitted for PE, 158 patients also had ILD. The mean age was 63.6 years for those without ILD (SD, 0.1) and 66.5 years for those with ILD (SD, 1.3).

Admission with ILD was associated with all-cause readmission (odds ratio [OR], 4.12; P < .01), in-hospital mortality (OR, 2.17; P = .01), a longer length of stay (+2.07 days; P < .01), and higher hospitalization charges (+$22,627; P < .01).

In the Q&A period after the presentation, Parth Rali, MD, professor of thoracic medicine and surgery at Temple University, Philadelphia, suggested phenotyping patients to better understand the location of the PE in relation to the ILD. “It may not fall into your classic PE classification. It may just depend on where the clot is in relationship to the interstitial lung disease. I think that’s where the field is going to evolve,” he later said in an interview.

“What is interesting is that patients with interstitial lung disease have a lot of fibrotic disease, and they do not need to have a large clot burden to make them sick. An example [is someone] who has undergone a lung transplant evaluation, and if their right lung is completely diseased from interstitial lung disease and if they get a big blood clot on the right side, it doesn’t affect them because the lung is already fibrotic, so the clot doesn’t matter. If they get a small clot [in the left lung], even though if you look at the standard PE classification they may qualify as a low-risk PE or even as an intermediate-low-risk PE, they are much sicker because that’s the functioning part of the lung,” said Rali.

He advised physicians to pay close attention to the location of PEs in relation to fibrotic tissue in patients with ILD. A PE in healthy lung tissue could have an outsized effect on hemodynamics, whereas a PE in fibrotic tissue may be clinically insignificant and not require treatment. “So it goes both ways: You don’t overtreat and you don’t undertreat,” Rali said.

Yuan and Rali disclosed no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

BOSTON — Patients with pulmonary embolism (PE) who also present with interstitial lung disease (ILD) have worse outcomes with respect to in-hospital mortality, length of hospital stay, hospital cost, and all-cause readmission, according to results from a new retrospective analysis.

“There’s a lot of evidence now that demonstrates that ILD, in general, leads to worse mortality, morbidity in hospital complications, and overall [outcomes]. It’s not hard to extrapolate this to pulmonary embolism outcomes, too. Unfortunately, there’s not a whole lot of evidence out there to really demonstrate it,” Leah Yuan, MD, said during a presentation of the results at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.

The question is complicated by the nebulous nature of ILD, which includes a diverse set of diseases and etiologies, and different levels of inflammation and fibrosis. It has been employed in the Pulmonary Embolism Severity Index but counts for only 10 points out of 210. “If you look at ILD and PE outcomes, there’s nothing really out there [in the literature],” Yuan said in an interview. She is a resident physician at Cook County Health and Hospitals System.

The new study suggested that ILD could have an important influence and perhaps should have greater weight in risk stratification of patients with PE, she said. “We looked at all-cause readmissions and we looked at in-hospital mortality, [both] of which are significant for increased odds ratio. One thing that I’m very curious to see is whether there is increased PE readmissions [associated with ILD], which is something that we couldn’t find to be significant in our study,” said Yuan.

The researchers used data from hospitalizations for PE drawn from the Nationwide Readmissions Database in 2019, using International Classification of Diseases, Tenth Revision, codes to identify admissions. Among a total of 105,133 patients admitted for PE, 158 patients also had ILD. The mean age was 63.6 years for those without ILD (SD, 0.1) and 66.5 years for those with ILD (SD, 1.3).

Admission with ILD was associated with all-cause readmission (odds ratio [OR], 4.12; P < .01), in-hospital mortality (OR, 2.17; P = .01), a longer length of stay (+2.07 days; P < .01), and higher hospitalization charges (+$22,627; P < .01).

In the Q&A period after the presentation, Parth Rali, MD, professor of thoracic medicine and surgery at Temple University, Philadelphia, suggested phenotyping patients to better understand the location of the PE in relation to the ILD. “It may not fall into your classic PE classification. It may just depend on where the clot is in relationship to the interstitial lung disease. I think that’s where the field is going to evolve,” he later said in an interview.

“What is interesting is that patients with interstitial lung disease have a lot of fibrotic disease, and they do not need to have a large clot burden to make them sick. An example [is someone] who has undergone a lung transplant evaluation, and if their right lung is completely diseased from interstitial lung disease and if they get a big blood clot on the right side, it doesn’t affect them because the lung is already fibrotic, so the clot doesn’t matter. If they get a small clot [in the left lung], even though if you look at the standard PE classification they may qualify as a low-risk PE or even as an intermediate-low-risk PE, they are much sicker because that’s the functioning part of the lung,” said Rali.

He advised physicians to pay close attention to the location of PEs in relation to fibrotic tissue in patients with ILD. A PE in healthy lung tissue could have an outsized effect on hemodynamics, whereas a PE in fibrotic tissue may be clinically insignificant and not require treatment. “So it goes both ways: You don’t overtreat and you don’t undertreat,” Rali said.

Yuan and Rali disclosed no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

BOSTON — The use of sodium-glucose cotransporter-2 (SGLT2) inhibitors is associated with reduced short- and long-term mortality among patients with pulmonary arterial hypertension (PAH), according to results from a new propensity score–matched analysis.

“There are a lot of new studies that show benefits [of SGLT2 inhibitors] in heart failure, in [chronic kidney disease], and of course, in diabetes. Group one pulmonary hypertension includes not only the inflammatory cascades but also fibrotic and neurovascularization, and all these different parts of the pathophysiology are linked to each other. There are studies that show that SGLT2 inhibitors can have an impact on inflammatory cascades, fibrosis, and vascular remodeling in general. Together, all this data triggered this idea for me, and that’s when I decided to conduct further studies,” said Irakli Lemonjava, MD, who presented the study at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.

The researchers drew data on 125,634 adult patients from the TriNetX database who were diagnosed with PAH after January 1, 2013. They used propensity score matching to account for demographic characteristics and 10 organ system disorders to compare patients with exposure to SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin; n = 6238) with those without such exposure (n = 6243).

At 1 year, 8.1% of patients taking SGLT2 inhibitors had died, compared with 15.5% of patients not taking SGLT2 inhibitors (risk reduction [RR], 0.52; P < .0001). The values were 13% and 22.5% (RR, 0.579; P < .0001) at 3 years and 14.6% and 25% at 5 years (RR, 0.583; P < .0001).

The study generated discussion during the Q&A period following the talk. One audience member asked if the group was able to access patients both inside and outside the United States. “Because I wonder if access to GLP2 inhibitors is actually a surrogate marker for access to other medications,” the questioner said.

Although the finding is intriguing, it shouldn’t change clinical practice, according to Lemonjava. “I don’t think we can make any changes based on what I shared today. Our purpose was to trigger the question. I think the numbers are so impressive that it will trigger more studies. I think if in the future it’s demonstrated by clinical trials that [SGLT2 inhibitors are beneficial], it will not be a problem to prescribe for someone with pulmonary arterial hypertension because they do not have many side effects,” he said. Lemonjava is a resident physician at Jefferson Einstein Philadelphia Hospital, Philadelphia.

Session co-moderator said Syed Rehan Quadery, MD, praised the study but emphasized the remaining uncertainty. “It’s an excellent proof of concept study. More trials need to [be done] on it, and we don’t understand the mechanism of action in which it improves survival in patients with pulmonary artery hypertension. The majority of the patients with pulmonary hypertension are much older and they have comorbidities, including cardiovascular risk factors, and maybe that is one of the ways in which this drug helps. Plus, there are multiple mechanisms in which it may be working, including anti-inflammatory as well as antiproliferative mechanisms through inhibiting the Notch-3 signaling pathway,” said Quadery, who is a consultant respiratory physician at National Pulmonary Hypertension Unit, Dublin, Ireland.

Quadery and his co-moderator Zeenat Safdar, MD, both noted that SGLT2 inhibitors have already been demonstrated to improve outcomes in heart failure. “[SGLT2 inhibition] improves survival, it decreases hospitalization, it improves morbidity and mortality. There are a lot of things that can be shown in different [animal or in vitro] models. In humans, we actually don’t know exactly how it works, but we know that it does. If it works in left heart failure, it also [could] work in right heart failure,” said Safdar, who is the director of the Houston Methodist Lung Center, Houston Methodist Hospital, Houston.

The study was independently supported. Lemonjava, Quadery, and Safdar reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

BOSTON — The use of sodium-glucose cotransporter-2 (SGLT2) inhibitors is associated with reduced short- and long-term mortality among patients with pulmonary arterial hypertension (PAH), according to results from a new propensity score–matched analysis.

“There are a lot of new studies that show benefits [of SGLT2 inhibitors] in heart failure, in [chronic kidney disease], and of course, in diabetes. Group one pulmonary hypertension includes not only the inflammatory cascades but also fibrotic and neurovascularization, and all these different parts of the pathophysiology are linked to each other. There are studies that show that SGLT2 inhibitors can have an impact on inflammatory cascades, fibrosis, and vascular remodeling in general. Together, all this data triggered this idea for me, and that’s when I decided to conduct further studies,” said Irakli Lemonjava, MD, who presented the study at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.

The researchers drew data on 125,634 adult patients from the TriNetX database who were diagnosed with PAH after January 1, 2013. They used propensity score matching to account for demographic characteristics and 10 organ system disorders to compare patients with exposure to SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin; n = 6238) with those without such exposure (n = 6243).

At 1 year, 8.1% of patients taking SGLT2 inhibitors had died, compared with 15.5% of patients not taking SGLT2 inhibitors (risk reduction [RR], 0.52; P < .0001). The values were 13% and 22.5% (RR, 0.579; P < .0001) at 3 years and 14.6% and 25% at 5 years (RR, 0.583; P < .0001).

The study generated discussion during the Q&A period following the talk. One audience member asked if the group was able to access patients both inside and outside the United States. “Because I wonder if access to GLP2 inhibitors is actually a surrogate marker for access to other medications,” the questioner said.

Although the finding is intriguing, it shouldn’t change clinical practice, according to Lemonjava. “I don’t think we can make any changes based on what I shared today. Our purpose was to trigger the question. I think the numbers are so impressive that it will trigger more studies. I think if in the future it’s demonstrated by clinical trials that [SGLT2 inhibitors are beneficial], it will not be a problem to prescribe for someone with pulmonary arterial hypertension because they do not have many side effects,” he said. Lemonjava is a resident physician at Jefferson Einstein Philadelphia Hospital, Philadelphia.

Session co-moderator said Syed Rehan Quadery, MD, praised the study but emphasized the remaining uncertainty. “It’s an excellent proof of concept study. More trials need to [be done] on it, and we don’t understand the mechanism of action in which it improves survival in patients with pulmonary artery hypertension. The majority of the patients with pulmonary hypertension are much older and they have comorbidities, including cardiovascular risk factors, and maybe that is one of the ways in which this drug helps. Plus, there are multiple mechanisms in which it may be working, including anti-inflammatory as well as antiproliferative mechanisms through inhibiting the Notch-3 signaling pathway,” said Quadery, who is a consultant respiratory physician at National Pulmonary Hypertension Unit, Dublin, Ireland.

Quadery and his co-moderator Zeenat Safdar, MD, both noted that SGLT2 inhibitors have already been demonstrated to improve outcomes in heart failure. “[SGLT2 inhibition] improves survival, it decreases hospitalization, it improves morbidity and mortality. There are a lot of things that can be shown in different [animal or in vitro] models. In humans, we actually don’t know exactly how it works, but we know that it does. If it works in left heart failure, it also [could] work in right heart failure,” said Safdar, who is the director of the Houston Methodist Lung Center, Houston Methodist Hospital, Houston.

The study was independently supported. Lemonjava, Quadery, and Safdar reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

BOSTON — The use of sodium-glucose cotransporter-2 (SGLT2) inhibitors is associated with reduced short- and long-term mortality among patients with pulmonary arterial hypertension (PAH), according to results from a new propensity score–matched analysis.

“There are a lot of new studies that show benefits [of SGLT2 inhibitors] in heart failure, in [chronic kidney disease], and of course, in diabetes. Group one pulmonary hypertension includes not only the inflammatory cascades but also fibrotic and neurovascularization, and all these different parts of the pathophysiology are linked to each other. There are studies that show that SGLT2 inhibitors can have an impact on inflammatory cascades, fibrosis, and vascular remodeling in general. Together, all this data triggered this idea for me, and that’s when I decided to conduct further studies,” said Irakli Lemonjava, MD, who presented the study at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.

The researchers drew data on 125,634 adult patients from the TriNetX database who were diagnosed with PAH after January 1, 2013. They used propensity score matching to account for demographic characteristics and 10 organ system disorders to compare patients with exposure to SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin; n = 6238) with those without such exposure (n = 6243).

At 1 year, 8.1% of patients taking SGLT2 inhibitors had died, compared with 15.5% of patients not taking SGLT2 inhibitors (risk reduction [RR], 0.52; P < .0001). The values were 13% and 22.5% (RR, 0.579; P < .0001) at 3 years and 14.6% and 25% at 5 years (RR, 0.583; P < .0001).

The study generated discussion during the Q&A period following the talk. One audience member asked if the group was able to access patients both inside and outside the United States. “Because I wonder if access to GLP2 inhibitors is actually a surrogate marker for access to other medications,” the questioner said.

Although the finding is intriguing, it shouldn’t change clinical practice, according to Lemonjava. “I don’t think we can make any changes based on what I shared today. Our purpose was to trigger the question. I think the numbers are so impressive that it will trigger more studies. I think if in the future it’s demonstrated by clinical trials that [SGLT2 inhibitors are beneficial], it will not be a problem to prescribe for someone with pulmonary arterial hypertension because they do not have many side effects,” he said. Lemonjava is a resident physician at Jefferson Einstein Philadelphia Hospital, Philadelphia.

Session co-moderator said Syed Rehan Quadery, MD, praised the study but emphasized the remaining uncertainty. “It’s an excellent proof of concept study. More trials need to [be done] on it, and we don’t understand the mechanism of action in which it improves survival in patients with pulmonary artery hypertension. The majority of the patients with pulmonary hypertension are much older and they have comorbidities, including cardiovascular risk factors, and maybe that is one of the ways in which this drug helps. Plus, there are multiple mechanisms in which it may be working, including anti-inflammatory as well as antiproliferative mechanisms through inhibiting the Notch-3 signaling pathway,” said Quadery, who is a consultant respiratory physician at National Pulmonary Hypertension Unit, Dublin, Ireland.

Quadery and his co-moderator Zeenat Safdar, MD, both noted that SGLT2 inhibitors have already been demonstrated to improve outcomes in heart failure. “[SGLT2 inhibition] improves survival, it decreases hospitalization, it improves morbidity and mortality. There are a lot of things that can be shown in different [animal or in vitro] models. In humans, we actually don’t know exactly how it works, but we know that it does. If it works in left heart failure, it also [could] work in right heart failure,” said Safdar, who is the director of the Houston Methodist Lung Center, Houston Methodist Hospital, Houston.

The study was independently supported. Lemonjava, Quadery, and Safdar reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

WASHINGTON — Combining short-term androgen deprivation therapy (ADT) with high-dose radiotherapy improves disease-free survival in men with intermediate-risk prostate cancer, compared with high-dose radiotherapy alone, according to results of the phase 3 GETUG 14 trial.

The 5-year disease-free survival rate was 84% in patients who received short-term ADT plus radiotherapy, compared with 76% in those who received radiotherapy alone.

In addition, short-term ADT with high-dose radiotherapy didn’t increase genitourinary or gastrointestinal toxicities, said Nicolas Demogeot, MD, with the Cancer Institute of Lorraine, Vandœuvre-lès-Nancy, France, who presented the results at the annual meeting of the American Society for Radiation Oncology (ASTRO).

Adding short-term ADT to standard-dose radiotherapy has been shown to improve all clinical outcomes, Dr. Demogeot noted, but few trials have tested it with high-dose radiotherapy. GETUG 14 was designed to do just that.

The multicenter, randomized, phase 3 trial enrolled 376 patients with intermediate- or high-risk localized prostate cancer who had PSA levels under 30 ng/mL and no clinical involvement of the seminal vesicles.

Patients were randomly allocated to high-dose radiotherapy (80 Gy) alone or high-dose radiotherapy plus monthly triptorelin and daily flutamide for a total duration of 4 months, starting 2 months prior to radiotherapy.

Disease-free survival was the primary endpoint. Secondary endpoints were overall survival, biochemical failure, metastasis failure, toxicity, and quality of life.

The modified intention-to-treat cohort included 191 patients in the radiotherapy-only group and 179 in the short-term ADT plus radiotherapy group. The two groups were well balanced. In both, patients ranged in age from 64 to 73 years; about two thirds had intermediate-risk disease; 70% received three-dimensional conformal radiotherapy, and 30% received intensity-modulated radiotherapy.

Overall, adding short-term ADT to high-dose radiotherapy was associated with a 36% relative improvement in 5-year disease-free survival (84% vs 76% with radiotherapy alone, hazard ratio [HR], 0.64; P = .02).

In subgroup analyses, intermediate-risk patients who received short-term ADT with high-dose radiotherapy demonstrated a significant improvement in disease-free survival (87% vs 74% with radiotherapy alone; HR, 0.55; P = .02). However, there was no significant disease-free survival benefit with short-term ADT with high-dose radiotherapy in high-risk patients (79% vs 75%; HR, 0.76; P = .40).

On multivariable analysis, short-term ADT with high-dose radiotherapy was associated with significant disease-free survival benefits (HR, 0.66; P = .038).

Patients who received short-term ADT with high-dose radiotherapy were significantly less likely to experience biochemical failure (10% vs 21%; HR, 0.45; P = .001), but there was no significant difference in metastasis failure (HR, 0.5; P = .09) or overall survival (HR, 1.22; P = .54).

As for adverse events, the two groups did not demonstrate significant differences in the proportions of early or late grade 2 or higher gastrointestinal or genitourinary toxicities.

Patients in the short-term ADT with high-dose radiotherapy group did experience a greater frequency of early grade 2 or higher erectile dysfunction (31% vs 6%; P < .001), but not late grade 2 or higher erectile dysfunction (63% vs 61%; P = .89).

Limitations of the study include a low power to detect differences between intermediate- and high-risk patients and the short follow-up period.

The GETUG 14 trial “confirms that short-term ADT improves disease-free survival when combined with dose-escalated radiation therapy for intermediate-risk prostate cancer,” Mark A. Hallman, MD, PhD, with Fox Chase Cancer Center, Philadelphia, Pennsylvania, who was not involved in the study, said in an interview. “However, there was not a similar benefit among the smaller subpopulation with high-risk disease.”

Outside expert Amar Kishan, MD, radiation oncologist, UCLA Jonsson Comprehensive Cancer Center, agreed, adding that “it is also reassuring to see no increase in genitourinary or gastrointestinal toxicity and no longer-term impact on erectile dysfunction.”

The GETUG-14 trial was supported by the French Ministry of Health and Ipsen. Dr. Demogeot has disclosed relationships with Ipsen, Janssen, Accord Healthcare, Astellas, and Bayer. Dr. Hallman had no relevant disclosures. Dr. Kishan has disclosed relationships with Boston Scientific, Janssen, Varian Medical Systems, ViewRay, and POINT Biopharma.

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

WASHINGTON — Combining short-term androgen deprivation therapy (ADT) with high-dose radiotherapy improves disease-free survival in men with intermediate-risk prostate cancer, compared with high-dose radiotherapy alone, according to results of the phase 3 GETUG 14 trial.

The 5-year disease-free survival rate was 84% in patients who received short-term ADT plus radiotherapy, compared with 76% in those who received radiotherapy alone.

In addition, short-term ADT with high-dose radiotherapy didn’t increase genitourinary or gastrointestinal toxicities, said Nicolas Demogeot, MD, with the Cancer Institute of Lorraine, Vandœuvre-lès-Nancy, France, who presented the results at the annual meeting of the American Society for Radiation Oncology (ASTRO).

Adding short-term ADT to standard-dose radiotherapy has been shown to improve all clinical outcomes, Dr. Demogeot noted, but few trials have tested it with high-dose radiotherapy. GETUG 14 was designed to do just that.

The multicenter, randomized, phase 3 trial enrolled 376 patients with intermediate- or high-risk localized prostate cancer who had PSA levels under 30 ng/mL and no clinical involvement of the seminal vesicles.

Patients were randomly allocated to high-dose radiotherapy (80 Gy) alone or high-dose radiotherapy plus monthly triptorelin and daily flutamide for a total duration of 4 months, starting 2 months prior to radiotherapy.

Disease-free survival was the primary endpoint. Secondary endpoints were overall survival, biochemical failure, metastasis failure, toxicity, and quality of life.

The modified intention-to-treat cohort included 191 patients in the radiotherapy-only group and 179 in the short-term ADT plus radiotherapy group. The two groups were well balanced. In both, patients ranged in age from 64 to 73 years; about two thirds had intermediate-risk disease; 70% received three-dimensional conformal radiotherapy, and 30% received intensity-modulated radiotherapy.

Overall, adding short-term ADT to high-dose radiotherapy was associated with a 36% relative improvement in 5-year disease-free survival (84% vs 76% with radiotherapy alone, hazard ratio [HR], 0.64; P = .02).

In subgroup analyses, intermediate-risk patients who received short-term ADT with high-dose radiotherapy demonstrated a significant improvement in disease-free survival (87% vs 74% with radiotherapy alone; HR, 0.55; P = .02). However, there was no significant disease-free survival benefit with short-term ADT with high-dose radiotherapy in high-risk patients (79% vs 75%; HR, 0.76; P = .40).

On multivariable analysis, short-term ADT with high-dose radiotherapy was associated with significant disease-free survival benefits (HR, 0.66; P = .038).

Patients who received short-term ADT with high-dose radiotherapy were significantly less likely to experience biochemical failure (10% vs 21%; HR, 0.45; P = .001), but there was no significant difference in metastasis failure (HR, 0.5; P = .09) or overall survival (HR, 1.22; P = .54).

As for adverse events, the two groups did not demonstrate significant differences in the proportions of early or late grade 2 or higher gastrointestinal or genitourinary toxicities.

Patients in the short-term ADT with high-dose radiotherapy group did experience a greater frequency of early grade 2 or higher erectile dysfunction (31% vs 6%; P < .001), but not late grade 2 or higher erectile dysfunction (63% vs 61%; P = .89).

Limitations of the study include a low power to detect differences between intermediate- and high-risk patients and the short follow-up period.

The GETUG 14 trial “confirms that short-term ADT improves disease-free survival when combined with dose-escalated radiation therapy for intermediate-risk prostate cancer,” Mark A. Hallman, MD, PhD, with Fox Chase Cancer Center, Philadelphia, Pennsylvania, who was not involved in the study, said in an interview. “However, there was not a similar benefit among the smaller subpopulation with high-risk disease.”

Outside expert Amar Kishan, MD, radiation oncologist, UCLA Jonsson Comprehensive Cancer Center, agreed, adding that “it is also reassuring to see no increase in genitourinary or gastrointestinal toxicity and no longer-term impact on erectile dysfunction.”

The GETUG-14 trial was supported by the French Ministry of Health and Ipsen. Dr. Demogeot has disclosed relationships with Ipsen, Janssen, Accord Healthcare, Astellas, and Bayer. Dr. Hallman had no relevant disclosures. Dr. Kishan has disclosed relationships with Boston Scientific, Janssen, Varian Medical Systems, ViewRay, and POINT Biopharma.

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

WASHINGTON — Combining short-term androgen deprivation therapy (ADT) with high-dose radiotherapy improves disease-free survival in men with intermediate-risk prostate cancer, compared with high-dose radiotherapy alone, according to results of the phase 3 GETUG 14 trial.

The 5-year disease-free survival rate was 84% in patients who received short-term ADT plus radiotherapy, compared with 76% in those who received radiotherapy alone.

In addition, short-term ADT with high-dose radiotherapy didn’t increase genitourinary or gastrointestinal toxicities, said Nicolas Demogeot, MD, with the Cancer Institute of Lorraine, Vandœuvre-lès-Nancy, France, who presented the results at the annual meeting of the American Society for Radiation Oncology (ASTRO).

Adding short-term ADT to standard-dose radiotherapy has been shown to improve all clinical outcomes, Dr. Demogeot noted, but few trials have tested it with high-dose radiotherapy. GETUG 14 was designed to do just that.

The multicenter, randomized, phase 3 trial enrolled 376 patients with intermediate- or high-risk localized prostate cancer who had PSA levels under 30 ng/mL and no clinical involvement of the seminal vesicles.

Patients were randomly allocated to high-dose radiotherapy (80 Gy) alone or high-dose radiotherapy plus monthly triptorelin and daily flutamide for a total duration of 4 months, starting 2 months prior to radiotherapy.

Disease-free survival was the primary endpoint. Secondary endpoints were overall survival, biochemical failure, metastasis failure, toxicity, and quality of life.

The modified intention-to-treat cohort included 191 patients in the radiotherapy-only group and 179 in the short-term ADT plus radiotherapy group. The two groups were well balanced. In both, patients ranged in age from 64 to 73 years; about two thirds had intermediate-risk disease; 70% received three-dimensional conformal radiotherapy, and 30% received intensity-modulated radiotherapy.

Overall, adding short-term ADT to high-dose radiotherapy was associated with a 36% relative improvement in 5-year disease-free survival (84% vs 76% with radiotherapy alone, hazard ratio [HR], 0.64; P = .02).

In subgroup analyses, intermediate-risk patients who received short-term ADT with high-dose radiotherapy demonstrated a significant improvement in disease-free survival (87% vs 74% with radiotherapy alone; HR, 0.55; P = .02). However, there was no significant disease-free survival benefit with short-term ADT with high-dose radiotherapy in high-risk patients (79% vs 75%; HR, 0.76; P = .40).

On multivariable analysis, short-term ADT with high-dose radiotherapy was associated with significant disease-free survival benefits (HR, 0.66; P = .038).

Patients who received short-term ADT with high-dose radiotherapy were significantly less likely to experience biochemical failure (10% vs 21%; HR, 0.45; P = .001), but there was no significant difference in metastasis failure (HR, 0.5; P = .09) or overall survival (HR, 1.22; P = .54).

As for adverse events, the two groups did not demonstrate significant differences in the proportions of early or late grade 2 or higher gastrointestinal or genitourinary toxicities.

Patients in the short-term ADT with high-dose radiotherapy group did experience a greater frequency of early grade 2 or higher erectile dysfunction (31% vs 6%; P < .001), but not late grade 2 or higher erectile dysfunction (63% vs 61%; P = .89).

Limitations of the study include a low power to detect differences between intermediate- and high-risk patients and the short follow-up period.

The GETUG 14 trial “confirms that short-term ADT improves disease-free survival when combined with dose-escalated radiation therapy for intermediate-risk prostate cancer,” Mark A. Hallman, MD, PhD, with Fox Chase Cancer Center, Philadelphia, Pennsylvania, who was not involved in the study, said in an interview. “However, there was not a similar benefit among the smaller subpopulation with high-risk disease.”

Outside expert Amar Kishan, MD, radiation oncologist, UCLA Jonsson Comprehensive Cancer Center, agreed, adding that “it is also reassuring to see no increase in genitourinary or gastrointestinal toxicity and no longer-term impact on erectile dysfunction.”

The GETUG-14 trial was supported by the French Ministry of Health and Ipsen. Dr. Demogeot has disclosed relationships with Ipsen, Janssen, Accord Healthcare, Astellas, and Bayer. Dr. Hallman had no relevant disclosures. Dr. Kishan has disclosed relationships with Boston Scientific, Janssen, Varian Medical Systems, ViewRay, and POINT Biopharma.

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

HUNTINGTON BEACH, CALIFORNIA — When patients of Aaron Mangold, MD, first learn they have mycosis fungoides (MF), the most common form of primary cutaneous T-cell lymphoma (CTCL), some are concerned about whether the diagnosis means a shortened life expectancy.

“In most cases, mycosis fungoides will not shorten one’s life, but it can cause significant symptoms,” Dr. Mangold, codirector of the multidisciplinary cutaneous lymphoma clinic at Mayo Clinic, Scottsdale, Arizona, said at the annual meeting of the Pacific Dermatologic Association. “For early-stage disease, I think of it more like diabetes; this is really a chronic disease” that unlikely will be fatal but may be associated with increased morbidity as the disease progresses, and “the overall goal of therapy should be disease control to increase quality of life.”

courtesy Dr. Aaron Mangold

Patient- and lymphoma-specific factors drive the choice of therapy. The focus for patients with early-stage disease, Dr. Mangold said, is to treat comorbidities and symptoms, such as itch or skin pain, maximize their quality of life, and consider the potential for associated toxicities of therapy as the disease progresses. Start with the least toxic, targeted, nonimmunosuppressive therapy, “then work toward more toxic immunosuppressive therapies,” he advised. “Use toxic agents just long enough to control the disease, then transition to a maintenance regimen with less toxic immunosuppressive agents.”
 

When Close Follow-Up Is Advised

According to unpublished data from PROCLIPI (the Prospective Cutaneous Lymphoma International Prognostic Index) study presented at the fifth World Congress of Cutaneous Lymphomas earlier in 2024, the following factors warrant consideration for close follow-up and more aggressive treatment: Nodal enlargement greater than 15 mm, age over 60 years, presence of plaques, and large-cell transformation in skin. “These are some of the stigmata in early disease that might guide you toward referring” a patient to a CTCL expert, Dr. Mangold said. (Consensus-based recommendations on the management of MF in children were published in August of 2024.)

According to Dr. Mangold, topical/skin-directed therapies are best for early-stage disease or in combination with systemic therapies in advanced disease. For early-stage disease, one of his preferred options is daily application of a skin moisturizer plus a topical corticosteroid such as clobetasol, halobetasol, or augmented betamethasone, then evaluating the response at 3 months. “This is a cheap option, and we see response rates as high as 90%,” he said. “I don’t often see steroid atrophy when treating patients with active MF. There’s a tendency to think, ‘I don’t want to overtreat.’ I think you can be aggressive. If you look in the literature, people typically pulse twice daily for a couple of weeks with a 1-week break.”

Mechlorethamine, a topical alkylating gel approved in 2013 for the treatment of early-stage MF, is an option when patients fail to respond to topical steroids, prefer to avoid steroids, or have thick, plaque-like disease. With mechlorethamine, it is important to “start slow and be patient,” Dr. Mangold said. “Real-world data shows that it takes 12-18 months to get a good response. Counsel patients that they are likely to get a rash, and that the risk of rash is dose dependent.”

Other treatment options to consider include imiquimod, which can be used for single refractory spots. He typically recommends application 5 days per week with titration up to daily if tolerated for up to 3 months. “Treat until you get a brisk immune response,” he said. “We’ve seen patients with durable, long-term responses.”
 

UVB Phototherapy Effective

For patients with stage IB disease, topical therapies are less practical and may be focused on refractory areas of disease. Narrow-band UVB phototherapy is the most practical and cost-effective treatment, Dr. Mangold said. Earlier-stage patch disease responds to phototherapy in up to 80% of cases, while plaque-stage disease responds in up to half of cases. “More frequent use of phototherapy may decrease time to clearance, but overall response is similar.”

Dr. Mangold recommends phototherapy 2-3 days per week, titrating up to a maximal response dose, and maintaining that dose for about 3 months. Maintenance involves tapering the phototherapy dose to a minimal dose with continued response. “The goal is to prevent relapse,” he said.

For patients with MF of stage IIB and higher, he considers total skin electron beam therapy, an oral retinoid with phototherapy, systemic agents, and focal radiation with systemic treatment. One of his go-to systemic options is bexarotene, which he uses for early-stage disease refractory to treatment or for less aggressive advanced disease. “We typically use a low dose ... and about half of patients respond,” Dr. Mangold said. The time to response is about 6 months. Bexarotene causes elevated lipids and low thyroid function, so he initiates patients on fenofibrate and levothyroxine at baseline.

Another systemic option is brentuximab vedotin, a monoclonal antibody that targets cells with CD30 expression, which is typically administered in a specialty center every 3 weeks for up to 16 cycles. “In practice, we often use six to eight cycles to avoid neuropathy,” he said. “It’s a good debulking agent, the time to response is 6-9 weeks, and it has a sustained response of 60%.” Neuropathy can occur with treatment, but improves over time.

Other systemic options for MF include romidepsin, mogamulizumab, and extracorporeal photopheresis used in erythrodermic disease.
 

Radiation An Option in Some Cases

Dr. Mangold noted that low doses of radiation therapy can effectively treat MF lesions in as little as one dose. “We can use it as a cure for a single spot or to temporarily treat the disease while other therapies are being started,” he said. Long-term side effects need to be considered when using radiation. “The more radiation, the more side effects.”

Dr. Mangold disclosed that he is an investigator for Sun Pharmaceutical, Solagenix, Elorac, miRagen, Kyowa Kirin, the National Clinical Trials Network, and CRISPR Therapeutics. He has also received consulting fees/honoraria from Kirin and Solagenix.

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

HUNTINGTON BEACH, CALIFORNIA — When patients of Aaron Mangold, MD, first learn they have mycosis fungoides (MF), the most common form of primary cutaneous T-cell lymphoma (CTCL), some are concerned about whether the diagnosis means a shortened life expectancy.

“In most cases, mycosis fungoides will not shorten one’s life, but it can cause significant symptoms,” Dr. Mangold, codirector of the multidisciplinary cutaneous lymphoma clinic at Mayo Clinic, Scottsdale, Arizona, said at the annual meeting of the Pacific Dermatologic Association. “For early-stage disease, I think of it more like diabetes; this is really a chronic disease” that unlikely will be fatal but may be associated with increased morbidity as the disease progresses, and “the overall goal of therapy should be disease control to increase quality of life.”

courtesy Dr. Aaron Mangold

Patient- and lymphoma-specific factors drive the choice of therapy. The focus for patients with early-stage disease, Dr. Mangold said, is to treat comorbidities and symptoms, such as itch or skin pain, maximize their quality of life, and consider the potential for associated toxicities of therapy as the disease progresses. Start with the least toxic, targeted, nonimmunosuppressive therapy, “then work toward more toxic immunosuppressive therapies,” he advised. “Use toxic agents just long enough to control the disease, then transition to a maintenance regimen with less toxic immunosuppressive agents.”
 

When Close Follow-Up Is Advised

According to unpublished data from PROCLIPI (the Prospective Cutaneous Lymphoma International Prognostic Index) study presented at the fifth World Congress of Cutaneous Lymphomas earlier in 2024, the following factors warrant consideration for close follow-up and more aggressive treatment: Nodal enlargement greater than 15 mm, age over 60 years, presence of plaques, and large-cell transformation in skin. “These are some of the stigmata in early disease that might guide you toward referring” a patient to a CTCL expert, Dr. Mangold said. (Consensus-based recommendations on the management of MF in children were published in August of 2024.)

According to Dr. Mangold, topical/skin-directed therapies are best for early-stage disease or in combination with systemic therapies in advanced disease. For early-stage disease, one of his preferred options is daily application of a skin moisturizer plus a topical corticosteroid such as clobetasol, halobetasol, or augmented betamethasone, then evaluating the response at 3 months. “This is a cheap option, and we see response rates as high as 90%,” he said. “I don’t often see steroid atrophy when treating patients with active MF. There’s a tendency to think, ‘I don’t want to overtreat.’ I think you can be aggressive. If you look in the literature, people typically pulse twice daily for a couple of weeks with a 1-week break.”

Mechlorethamine, a topical alkylating gel approved in 2013 for the treatment of early-stage MF, is an option when patients fail to respond to topical steroids, prefer to avoid steroids, or have thick, plaque-like disease. With mechlorethamine, it is important to “start slow and be patient,” Dr. Mangold said. “Real-world data shows that it takes 12-18 months to get a good response. Counsel patients that they are likely to get a rash, and that the risk of rash is dose dependent.”

Other treatment options to consider include imiquimod, which can be used for single refractory spots. He typically recommends application 5 days per week with titration up to daily if tolerated for up to 3 months. “Treat until you get a brisk immune response,” he said. “We’ve seen patients with durable, long-term responses.”
 

UVB Phototherapy Effective

For patients with stage IB disease, topical therapies are less practical and may be focused on refractory areas of disease. Narrow-band UVB phototherapy is the most practical and cost-effective treatment, Dr. Mangold said. Earlier-stage patch disease responds to phototherapy in up to 80% of cases, while plaque-stage disease responds in up to half of cases. “More frequent use of phototherapy may decrease time to clearance, but overall response is similar.”

Dr. Mangold recommends phototherapy 2-3 days per week, titrating up to a maximal response dose, and maintaining that dose for about 3 months. Maintenance involves tapering the phototherapy dose to a minimal dose with continued response. “The goal is to prevent relapse,” he said.

For patients with MF of stage IIB and higher, he considers total skin electron beam therapy, an oral retinoid with phototherapy, systemic agents, and focal radiation with systemic treatment. One of his go-to systemic options is bexarotene, which he uses for early-stage disease refractory to treatment or for less aggressive advanced disease. “We typically use a low dose ... and about half of patients respond,” Dr. Mangold said. The time to response is about 6 months. Bexarotene causes elevated lipids and low thyroid function, so he initiates patients on fenofibrate and levothyroxine at baseline.

Another systemic option is brentuximab vedotin, a monoclonal antibody that targets cells with CD30 expression, which is typically administered in a specialty center every 3 weeks for up to 16 cycles. “In practice, we often use six to eight cycles to avoid neuropathy,” he said. “It’s a good debulking agent, the time to response is 6-9 weeks, and it has a sustained response of 60%.” Neuropathy can occur with treatment, but improves over time.

Other systemic options for MF include romidepsin, mogamulizumab, and extracorporeal photopheresis used in erythrodermic disease.
 

Radiation An Option in Some Cases

Dr. Mangold noted that low doses of radiation therapy can effectively treat MF lesions in as little as one dose. “We can use it as a cure for a single spot or to temporarily treat the disease while other therapies are being started,” he said. Long-term side effects need to be considered when using radiation. “The more radiation, the more side effects.”

Dr. Mangold disclosed that he is an investigator for Sun Pharmaceutical, Solagenix, Elorac, miRagen, Kyowa Kirin, the National Clinical Trials Network, and CRISPR Therapeutics. He has also received consulting fees/honoraria from Kirin and Solagenix.

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

HUNTINGTON BEACH, CALIFORNIA — When patients of Aaron Mangold, MD, first learn they have mycosis fungoides (MF), the most common form of primary cutaneous T-cell lymphoma (CTCL), some are concerned about whether the diagnosis means a shortened life expectancy.

“In most cases, mycosis fungoides will not shorten one’s life, but it can cause significant symptoms,” Dr. Mangold, codirector of the multidisciplinary cutaneous lymphoma clinic at Mayo Clinic, Scottsdale, Arizona, said at the annual meeting of the Pacific Dermatologic Association. “For early-stage disease, I think of it more like diabetes; this is really a chronic disease” that unlikely will be fatal but may be associated with increased morbidity as the disease progresses, and “the overall goal of therapy should be disease control to increase quality of life.”

courtesy Dr. Aaron Mangold

Patient- and lymphoma-specific factors drive the choice of therapy. The focus for patients with early-stage disease, Dr. Mangold said, is to treat comorbidities and symptoms, such as itch or skin pain, maximize their quality of life, and consider the potential for associated toxicities of therapy as the disease progresses. Start with the least toxic, targeted, nonimmunosuppressive therapy, “then work toward more toxic immunosuppressive therapies,” he advised. “Use toxic agents just long enough to control the disease, then transition to a maintenance regimen with less toxic immunosuppressive agents.”
 

When Close Follow-Up Is Advised

According to unpublished data from PROCLIPI (the Prospective Cutaneous Lymphoma International Prognostic Index) study presented at the fifth World Congress of Cutaneous Lymphomas earlier in 2024, the following factors warrant consideration for close follow-up and more aggressive treatment: Nodal enlargement greater than 15 mm, age over 60 years, presence of plaques, and large-cell transformation in skin. “These are some of the stigmata in early disease that might guide you toward referring” a patient to a CTCL expert, Dr. Mangold said. (Consensus-based recommendations on the management of MF in children were published in August of 2024.)

According to Dr. Mangold, topical/skin-directed therapies are best for early-stage disease or in combination with systemic therapies in advanced disease. For early-stage disease, one of his preferred options is daily application of a skin moisturizer plus a topical corticosteroid such as clobetasol, halobetasol, or augmented betamethasone, then evaluating the response at 3 months. “This is a cheap option, and we see response rates as high as 90%,” he said. “I don’t often see steroid atrophy when treating patients with active MF. There’s a tendency to think, ‘I don’t want to overtreat.’ I think you can be aggressive. If you look in the literature, people typically pulse twice daily for a couple of weeks with a 1-week break.”

Mechlorethamine, a topical alkylating gel approved in 2013 for the treatment of early-stage MF, is an option when patients fail to respond to topical steroids, prefer to avoid steroids, or have thick, plaque-like disease. With mechlorethamine, it is important to “start slow and be patient,” Dr. Mangold said. “Real-world data shows that it takes 12-18 months to get a good response. Counsel patients that they are likely to get a rash, and that the risk of rash is dose dependent.”

Other treatment options to consider include imiquimod, which can be used for single refractory spots. He typically recommends application 5 days per week with titration up to daily if tolerated for up to 3 months. “Treat until you get a brisk immune response,” he said. “We’ve seen patients with durable, long-term responses.”
 

UVB Phototherapy Effective

For patients with stage IB disease, topical therapies are less practical and may be focused on refractory areas of disease. Narrow-band UVB phototherapy is the most practical and cost-effective treatment, Dr. Mangold said. Earlier-stage patch disease responds to phototherapy in up to 80% of cases, while plaque-stage disease responds in up to half of cases. “More frequent use of phototherapy may decrease time to clearance, but overall response is similar.”

Dr. Mangold recommends phototherapy 2-3 days per week, titrating up to a maximal response dose, and maintaining that dose for about 3 months. Maintenance involves tapering the phototherapy dose to a minimal dose with continued response. “The goal is to prevent relapse,” he said.

For patients with MF of stage IIB and higher, he considers total skin electron beam therapy, an oral retinoid with phototherapy, systemic agents, and focal radiation with systemic treatment. One of his go-to systemic options is bexarotene, which he uses for early-stage disease refractory to treatment or for less aggressive advanced disease. “We typically use a low dose ... and about half of patients respond,” Dr. Mangold said. The time to response is about 6 months. Bexarotene causes elevated lipids and low thyroid function, so he initiates patients on fenofibrate and levothyroxine at baseline.

Another systemic option is brentuximab vedotin, a monoclonal antibody that targets cells with CD30 expression, which is typically administered in a specialty center every 3 weeks for up to 16 cycles. “In practice, we often use six to eight cycles to avoid neuropathy,” he said. “It’s a good debulking agent, the time to response is 6-9 weeks, and it has a sustained response of 60%.” Neuropathy can occur with treatment, but improves over time.

Other systemic options for MF include romidepsin, mogamulizumab, and extracorporeal photopheresis used in erythrodermic disease.
 

Radiation An Option in Some Cases

Dr. Mangold noted that low doses of radiation therapy can effectively treat MF lesions in as little as one dose. “We can use it as a cure for a single spot or to temporarily treat the disease while other therapies are being started,” he said. Long-term side effects need to be considered when using radiation. “The more radiation, the more side effects.”

Dr. Mangold disclosed that he is an investigator for Sun Pharmaceutical, Solagenix, Elorac, miRagen, Kyowa Kirin, the National Clinical Trials Network, and CRISPR Therapeutics. He has also received consulting fees/honoraria from Kirin and Solagenix.

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

Adding isatuximab, or Isa (Sarclisa, Sanofi-Aventis), to bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of patients with newly diagnosed, transplant-ineligible multiple myeloma reduced the risk for disease progression or death by more than 40% vs VRd alone in the randomized, global, open-label, phase 3 IMROZ trial.

The findings, presented on September 26 at the annual meeting of the International Myeloma Society, support the four-drug combination known as Isa-VRd as a potential new standard of care (SOC) supplanting VRd alone as the SOC in this setting, according to Meletios Dimopoulos, MD, of the University of Athens, Greece.

The IMROZ findings — the first from a phase 3 study of an anti-CD38 monoclonal antibody given in combination with VRd — were also reported in May at the annual meeting of the American Society of Clinical Oncology (ASCO) and published simultaneously in The New England Journal of Medicine. 

“The significant progression-free benefit observed with Sarclisa with combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma,” first author Thierry Facon, MD, told this news organization at ASCO.

Dr. Thierry, of the University of Lille, and the French Academy of Medicine in Paris, France, added that Isa-VRd has the potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients.”

Isatuximab in combination with VRd was subsequently approved by the US Food and Drug Administration (FDA) for this indication, as reported on September 23 by this news organization.

So, what will this quadruplet mean for the treatment of multiple myeloma? IMROZ study coauthors Meral Beksac, MD, of Istinye University, Istanbul, and Liv Hospital Ankara, Turkey, and Mohamad Mohty, MD, of Sorbonne University, Saint-Antoine Hospital, Paris, France, provided some insights in a recent interview, telling the European Medical Journal (EMJ) Hematology that Isa-VRd is a “welcome addition” to the multiple myeloma armamentarium.
 

Should Isa-VRd Be Considered the New First-Choice Frontline Treatment for Transplant-Ineligible Patients?

“The short answer is yes,” Dr. Mohty told EMJ. “Based on this trial, quadruplet should become the preferred regimen in the population of patients represented by these inclusion criteria.”

Dr. Beksac agreed that Isa-VRd will play a role in frontline management for transplant-ineligible patients.

However, both noted that despite having a favorable safety profile similar to VRd, Isa-VRd may not be well tolerated in elderly and frail patients. Demonstrably frail patients were excluded from IMROZ, and this is a factor that should be considered in the practice setting, they agreed.
 

Will Isa-VRd Change How Patients Are Evaluated for Transplant Eligibility?

“The cutoff for transplant eligibility differs from one country to another, and today, we do not have consensus around an agreed-upon age limit,” Dr. Beksac said. “We further rely on frailty and the patient’s performance status, not only at diagnosis but at later stages as well.”

She also noted that “[t]he introduction of very effective systemic regimens with similar efficacy to [hematopoietic stem cell transplant (HSCT)] has seen a shift towards non-transplant regimens, particularly in the USA.”

“In many centers in Europe, these patients [in IMROZ] would be considered transplant eligible. Hence, for this group of patients who are not too old, but not too young, and fit, IMROZ is offering a non-transplant-based treatment with similar efficacy to what can be achieved with HSCT,” Dr. Mohty added.

Patient preference and access are also important considerations, as is cost, he noted.

Younger transplant-eligible patients may prefer transplant over continuous treatment for life, whereas some might prefer long-term treatment over a stem cell protocol that will require months off of work, he and Dr. Beksac explained.

“Based on this trial, we will likely see a decline in the number of transplants,” Dr. Mohty predicted. “With the IMROZ data, we have something valid that we can offer patients without any prejudice to their outcome.”
 

How Will This Combination Be Integrated Into Daily Clinical Practice?

“My interpretation would be that this protocol will be conceived as an applicable protocol that can be adapted to our daily practice,” Dr. Beksac said.

Dr. Mohty added that the multiple myeloma story is changing and evolving.

“It’s not transplant versus no transplant, it’s who is going to receive quadruplet and who’s going to receive less than a quadruplet, who is fit and who is unfit,” he explained, adding that physicians will likely adapt the Isa-VRd regimen for real-world use based on clinical judgment.

For example, the quadruplet may be combined “in a kind of VRd-light version to start with, and maybe we can adapt later depending on the tolerability of the patient,” Dr. Beksac added.

“Until recently, we thought that transplant is the gold standard for everybody whenever possible. Now, we have a more nuanced answer, offering a regimen that actually is as effective, and may even be better, than transplant,” Dr. Mohty said. “So, it’s a most welcome addition to what we do.”

Both the IMROZ study and the EMJ article were funded by Sanofi.

Dr. Dimopoulos reported ties with Amgen, BeiGene, BMS, Janssen, Sanofi, and Takeda. Dr. Beksac disclosed relationships with Amgen, BMS, GSK, Janssen, Sanofi, and Takeda. Dr. Mohty reported ties with Adaptive Biotechnologies, Amgen, Astellas Pharma, BMS, GSK, Janssen-Cilag, Jazz Pharmaceuticals, and others.
 

A version of this article appeared on Medscape.com.

Adding isatuximab, or Isa (Sarclisa, Sanofi-Aventis), to bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of patients with newly diagnosed, transplant-ineligible multiple myeloma reduced the risk for disease progression or death by more than 40% vs VRd alone in the randomized, global, open-label, phase 3 IMROZ trial.

The findings, presented on September 26 at the annual meeting of the International Myeloma Society, support the four-drug combination known as Isa-VRd as a potential new standard of care (SOC) supplanting VRd alone as the SOC in this setting, according to Meletios Dimopoulos, MD, of the University of Athens, Greece.

The IMROZ findings — the first from a phase 3 study of an anti-CD38 monoclonal antibody given in combination with VRd — were also reported in May at the annual meeting of the American Society of Clinical Oncology (ASCO) and published simultaneously in The New England Journal of Medicine. 

“The significant progression-free benefit observed with Sarclisa with combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma,” first author Thierry Facon, MD, told this news organization at ASCO.

Dr. Thierry, of the University of Lille, and the French Academy of Medicine in Paris, France, added that Isa-VRd has the potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients.”

Isatuximab in combination with VRd was subsequently approved by the US Food and Drug Administration (FDA) for this indication, as reported on September 23 by this news organization.

So, what will this quadruplet mean for the treatment of multiple myeloma? IMROZ study coauthors Meral Beksac, MD, of Istinye University, Istanbul, and Liv Hospital Ankara, Turkey, and Mohamad Mohty, MD, of Sorbonne University, Saint-Antoine Hospital, Paris, France, provided some insights in a recent interview, telling the European Medical Journal (EMJ) Hematology that Isa-VRd is a “welcome addition” to the multiple myeloma armamentarium.
 

Should Isa-VRd Be Considered the New First-Choice Frontline Treatment for Transplant-Ineligible Patients?

“The short answer is yes,” Dr. Mohty told EMJ. “Based on this trial, quadruplet should become the preferred regimen in the population of patients represented by these inclusion criteria.”

Dr. Beksac agreed that Isa-VRd will play a role in frontline management for transplant-ineligible patients.

However, both noted that despite having a favorable safety profile similar to VRd, Isa-VRd may not be well tolerated in elderly and frail patients. Demonstrably frail patients were excluded from IMROZ, and this is a factor that should be considered in the practice setting, they agreed.
 

Will Isa-VRd Change How Patients Are Evaluated for Transplant Eligibility?

“The cutoff for transplant eligibility differs from one country to another, and today, we do not have consensus around an agreed-upon age limit,” Dr. Beksac said. “We further rely on frailty and the patient’s performance status, not only at diagnosis but at later stages as well.”

She also noted that “[t]he introduction of very effective systemic regimens with similar efficacy to [hematopoietic stem cell transplant (HSCT)] has seen a shift towards non-transplant regimens, particularly in the USA.”

“In many centers in Europe, these patients [in IMROZ] would be considered transplant eligible. Hence, for this group of patients who are not too old, but not too young, and fit, IMROZ is offering a non-transplant-based treatment with similar efficacy to what can be achieved with HSCT,” Dr. Mohty added.

Patient preference and access are also important considerations, as is cost, he noted.

Younger transplant-eligible patients may prefer transplant over continuous treatment for life, whereas some might prefer long-term treatment over a stem cell protocol that will require months off of work, he and Dr. Beksac explained.

“Based on this trial, we will likely see a decline in the number of transplants,” Dr. Mohty predicted. “With the IMROZ data, we have something valid that we can offer patients without any prejudice to their outcome.”
 

How Will This Combination Be Integrated Into Daily Clinical Practice?

“My interpretation would be that this protocol will be conceived as an applicable protocol that can be adapted to our daily practice,” Dr. Beksac said.

Dr. Mohty added that the multiple myeloma story is changing and evolving.

“It’s not transplant versus no transplant, it’s who is going to receive quadruplet and who’s going to receive less than a quadruplet, who is fit and who is unfit,” he explained, adding that physicians will likely adapt the Isa-VRd regimen for real-world use based on clinical judgment.

For example, the quadruplet may be combined “in a kind of VRd-light version to start with, and maybe we can adapt later depending on the tolerability of the patient,” Dr. Beksac added.

“Until recently, we thought that transplant is the gold standard for everybody whenever possible. Now, we have a more nuanced answer, offering a regimen that actually is as effective, and may even be better, than transplant,” Dr. Mohty said. “So, it’s a most welcome addition to what we do.”

Both the IMROZ study and the EMJ article were funded by Sanofi.

Dr. Dimopoulos reported ties with Amgen, BeiGene, BMS, Janssen, Sanofi, and Takeda. Dr. Beksac disclosed relationships with Amgen, BMS, GSK, Janssen, Sanofi, and Takeda. Dr. Mohty reported ties with Adaptive Biotechnologies, Amgen, Astellas Pharma, BMS, GSK, Janssen-Cilag, Jazz Pharmaceuticals, and others.
 

A version of this article appeared on Medscape.com.

Adding isatuximab, or Isa (Sarclisa, Sanofi-Aventis), to bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of patients with newly diagnosed, transplant-ineligible multiple myeloma reduced the risk for disease progression or death by more than 40% vs VRd alone in the randomized, global, open-label, phase 3 IMROZ trial.

The findings, presented on September 26 at the annual meeting of the International Myeloma Society, support the four-drug combination known as Isa-VRd as a potential new standard of care (SOC) supplanting VRd alone as the SOC in this setting, according to Meletios Dimopoulos, MD, of the University of Athens, Greece.

The IMROZ findings — the first from a phase 3 study of an anti-CD38 monoclonal antibody given in combination with VRd — were also reported in May at the annual meeting of the American Society of Clinical Oncology (ASCO) and published simultaneously in The New England Journal of Medicine. 

“The significant progression-free benefit observed with Sarclisa with combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma,” first author Thierry Facon, MD, told this news organization at ASCO.

Dr. Thierry, of the University of Lille, and the French Academy of Medicine in Paris, France, added that Isa-VRd has the potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients.”

Isatuximab in combination with VRd was subsequently approved by the US Food and Drug Administration (FDA) for this indication, as reported on September 23 by this news organization.

So, what will this quadruplet mean for the treatment of multiple myeloma? IMROZ study coauthors Meral Beksac, MD, of Istinye University, Istanbul, and Liv Hospital Ankara, Turkey, and Mohamad Mohty, MD, of Sorbonne University, Saint-Antoine Hospital, Paris, France, provided some insights in a recent interview, telling the European Medical Journal (EMJ) Hematology that Isa-VRd is a “welcome addition” to the multiple myeloma armamentarium.
 

Should Isa-VRd Be Considered the New First-Choice Frontline Treatment for Transplant-Ineligible Patients?

“The short answer is yes,” Dr. Mohty told EMJ. “Based on this trial, quadruplet should become the preferred regimen in the population of patients represented by these inclusion criteria.”

Dr. Beksac agreed that Isa-VRd will play a role in frontline management for transplant-ineligible patients.

However, both noted that despite having a favorable safety profile similar to VRd, Isa-VRd may not be well tolerated in elderly and frail patients. Demonstrably frail patients were excluded from IMROZ, and this is a factor that should be considered in the practice setting, they agreed.
 

Will Isa-VRd Change How Patients Are Evaluated for Transplant Eligibility?

“The cutoff for transplant eligibility differs from one country to another, and today, we do not have consensus around an agreed-upon age limit,” Dr. Beksac said. “We further rely on frailty and the patient’s performance status, not only at diagnosis but at later stages as well.”

She also noted that “[t]he introduction of very effective systemic regimens with similar efficacy to [hematopoietic stem cell transplant (HSCT)] has seen a shift towards non-transplant regimens, particularly in the USA.”

“In many centers in Europe, these patients [in IMROZ] would be considered transplant eligible. Hence, for this group of patients who are not too old, but not too young, and fit, IMROZ is offering a non-transplant-based treatment with similar efficacy to what can be achieved with HSCT,” Dr. Mohty added.

Patient preference and access are also important considerations, as is cost, he noted.

Younger transplant-eligible patients may prefer transplant over continuous treatment for life, whereas some might prefer long-term treatment over a stem cell protocol that will require months off of work, he and Dr. Beksac explained.

“Based on this trial, we will likely see a decline in the number of transplants,” Dr. Mohty predicted. “With the IMROZ data, we have something valid that we can offer patients without any prejudice to their outcome.”
 

How Will This Combination Be Integrated Into Daily Clinical Practice?

“My interpretation would be that this protocol will be conceived as an applicable protocol that can be adapted to our daily practice,” Dr. Beksac said.

Dr. Mohty added that the multiple myeloma story is changing and evolving.

“It’s not transplant versus no transplant, it’s who is going to receive quadruplet and who’s going to receive less than a quadruplet, who is fit and who is unfit,” he explained, adding that physicians will likely adapt the Isa-VRd regimen for real-world use based on clinical judgment.

For example, the quadruplet may be combined “in a kind of VRd-light version to start with, and maybe we can adapt later depending on the tolerability of the patient,” Dr. Beksac added.

“Until recently, we thought that transplant is the gold standard for everybody whenever possible. Now, we have a more nuanced answer, offering a regimen that actually is as effective, and may even be better, than transplant,” Dr. Mohty said. “So, it’s a most welcome addition to what we do.”

Both the IMROZ study and the EMJ article were funded by Sanofi.

Dr. Dimopoulos reported ties with Amgen, BeiGene, BMS, Janssen, Sanofi, and Takeda. Dr. Beksac disclosed relationships with Amgen, BMS, GSK, Janssen, Sanofi, and Takeda. Dr. Mohty reported ties with Adaptive Biotechnologies, Amgen, Astellas Pharma, BMS, GSK, Janssen-Cilag, Jazz Pharmaceuticals, and others.
 

A version of this article appeared on Medscape.com.