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Patients haunted by fears of living with and dying from severe lung disease
Many patients with chronic progressive pulmonary disease feel anxious and depressed as their conditions advance, as breathing becomes increasingly labored and difficult, and as performing even small daily tasks leaves them exhausted.
Persons with severe COPD frequently report fears of suffocation and death, as well as anxieties about abandoning family and friends, and these negative, intrusive thoughts can have an adverse effect on COPD outcomes.
Disease-related mental distress can lead to increased disability, more frequent use of costly health care resources, higher morbidity, and elevated risk of death, investigators say.
"Individuals with severe COPD are twice as likely to develop depression than patients with mild COPD. Prevalence rates for clinical anxiety in COPD range from 13% to 46% in outpatients and 10% to 55% among inpatients," wrote Abebaw Mengitsu Yohannes, PhD, then from Azusa Pacific University in Azusa, California and colleagues in an article published jointly by The Journal of Family Practice and The Cleveland Clinic Journal of Medicine.
Patients with COPD may experience major depressive disorders, chronic mild depression (dysthymias), and minor depression, as well as generalized anxiety disorder, phobias, and panic disorders, the investigators say.
"Growing evidence suggests that the relationship between mood disorders, particularly depression, and COPD is bidirectional, meaning that mood disorders adversely impact prognosis in COPD, whereas COPD increases the risk of developing depression," Yohannes et al wrote.
Jamie Garfield, MD, professor of thoracic medicine and surgery at Temple University's Lewis Katz School of Medicine in Philadelphia, told Chest Physician that the association between severe chronic diseases and mood disorders is well known.
"I don't think that it's specific to chronic lung diseases; in people with chronic heart disease or malignancies we see that co-existence of depression and anxiety will worsen the course of disease," she said.
Dr. Johannes, who is currently a professor of physical therapy at the University of Alabama School of Health Professionals in Birmingham, said that depression and anxiety are often underdiagnosed and undertreated in patients with obstructive pulmonary diseases because the conditions can share symptoms such as dyspnea (for example, in anxiety) or fatigue (in depression).
"Therefore, unless one begins to explore further, it's hard for physicians to be able to identify these conditions," he said in an interview with Chest Physician.
Fears of dying (and living)
The causes of depression and anxiety among patients with obstructive pulmonary disorders are multi-factorial, and may require a variety of treatment and coping strategies, according to Susann Strang, RN, PhD, and colleagues from the University of Gothenburg, Sweden.
They conducted qualitative in-depth interviews with 31 men and women with stage III or IV COPD, and found that the majority of patients had anxiety associated with their disease.
"Analyses revealed three major themes: death anxiety, life anxiety, and counterweights to anxiety," the investigators wrote in a study published in the journal Palliative and Supportive Care in 2014.
Factors contributing to anxiety surrounding death included fear of suffocation, awareness of impending death, fear of the process of death, and anxiety about being separated from loved ones.
In contrast, some patients expressed dread of living with the limitations and loneliness imposed on them by their disease, so called "life anxiety."
The patients also reported "counterweights" to anxiety as a way of coping. For some this involved trust in their health care professionals and adherence to medication, inhalers, and supplemental oxygen.
"The patients also placed hope in new treatments, better medication, surgery, stem cell treatment, or lung transplants," Dr. Strang and colleagues reported.
Others reported avoiding talking about death, sleeping more, or using humor to "laugh off this difficult subject."
Screening and diagnosis
Primary care practitioners are often the first health professionals that patients with COPD see, but these clinicians often don't have the time to add screening to their already crammed schedules. In addition, "the lack of a standardized approach in diagnosis, and inadequate knowledge or confidence in assessing psychological status (particularly given the number of strategies available for screening patients for mood disorders)," can make it difficult for PCPs to detect and manage anxiety and depression in their patients with significant health care burdens from COPD and other obstructive lung diseases, Dr. Yohannes and colleagues noted.
In addition to commonly used screening tools for anxiety and depression such as the Primary Care Evaluation of Mental Disorders (PRIME-MD) Patient Health Questionnaire (PHQ-9), there are at least two designed to evaluate patients with lung disease: the Anxiety Inventory for Respiratory (AIR) Disease scale, developed by Dr. Johannes and colleagues, and the COPD Anxiety Questionnaire.
The COPD Assessment Testand Clinical COPD Questionnaire, while not specifically designed to screen for mental disorders, include questions that can point to symptoms of distress in patients with COPD, Dr. Yohannes said.
"In truth I think that there are few providers who will routinely do this on all their patients in terms of quantifying the severity or the presence or absence of depression, but in my own practice I very much ask questions that align with the questions in these tools to determine whether my patient appears to have high levels of anxiety and depression," Dr. Garfield said.
Listen to patients and families
Among the most powerful tools that clinicians have at their disposal for treating anxiety and depression in patients with chronic lung disease are their ears and their minds, said Anthony Saleh, MD, a pulmonologist at New York-Presbyterian Brooklyn Methodist Hospital in Brooklyn, New York.
"I think just listening to the patient, that's a little bit forgotten yet so important," he said in an interview with Chest Physician.
"When I have someone with advanced lung disease, like idiopathic pulmonary fibrosis, like advanced emphysema, one of the most important things I think is to listen to the patient, and not just to listen to the answers of your perfunctory 'how's your breathing? Any chest pain?' and those sort of rote medical questions, but listen to their thoughts, and it will given them a safe space to say 'Hey, I'm nervous, hey I'm worried about my family, hey I'm worried if I die what's going to happen to my wife and kids,' and that's something I think is invaluable."
It's also vital to listen to the concerns of the patients family members, who may be the primary caregivers and may share the patient's stresses and anxieties, he said.
Pulmonary Rehabilitation
All of the experts interviewed for this article agreed that a combination of medical, social and mental health support services is important for treatment for patients with chronic obstructive lung diseases.
One of the most effective means of helping patients with both acute breathing problems and with disease-related anxiety and depression is pulmonary rehabilitation. Depending on disease severity, this multidisciplinary approach may involve exercise, patient education, psychological and nutrition counseling, and training patients how to conserve energy and adopt breathing strategies to help them better manage their symptoms.
"I think that pulmonary rehabilitation is one of the first interventions that we should be recommending for our patients," Dr. Garfield said. "It's physical therapy for patients with chronic lung diseases, backed by respiratory therapists, and it offers not only physical rehabilitation - improving strength and coordination, but also it helps our patients get as much as possible out of what they've got."
For example, patients can be taught how to decrease their respiratory rate when they're feeling a sense of urgency or panic. Patients can also learn how to change body positions to help them breathe more effectively when they feel that their breath is limited or restricted, she said.
"Once your into medical interventions, pulmonary rehab is phenomenal," Dr. Saleh said.
Pulmonary rehabilitation helps patients to feel better about themselves and about their abilities, but "unfortunately it's not as available as we like," he said.
Many patients don't live near a pulmonary rehabilitation center, and the typical two to three weekly sessions for 4 to 12 weeks or longer can be a significant burden for patients and caregivers, he acknowledged.
"You have to sit [with the patient] and be honest and tell them it's a lot of diligence involved and you have to be really motivated," he said.
Other treatment options include pharmacological therapy with antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and anxiolytic agents.
"SSRIs are the current first-line drug treatment for depression, and have been shown to significantly improve depression and anxiety in patients with COPD in some, but not all, trials published to date. However, it is important to note that a diagnosis of bipolar disorder must be ruled out before initiating standard antidepressant therapy," Dr. Johannes and colleagues wrote.
Defiant joy
Importantly, even with the burden of life with COPD, many patients found ways to experience what Strang et al called "a defiant joy."
"It was remarkable that when the patients were asked about what gave their lives meaning today, many talked about what had given their life meaning in the past, prior to becoming ill. In the light of the things they had lost because of the disease, many felt that their previous sources of joy no longer existed. Despite this, many still hoped to be able to get out into the fresh air, to be able to do errands or that tomorrow might be better," the investigators wrote.
Dr. Yohannes, Dr. Garfield, and Dr. Saleh all reported having no relevant conflicts of interest to report.
Many patients with chronic progressive pulmonary disease feel anxious and depressed as their conditions advance, as breathing becomes increasingly labored and difficult, and as performing even small daily tasks leaves them exhausted.
Persons with severe COPD frequently report fears of suffocation and death, as well as anxieties about abandoning family and friends, and these negative, intrusive thoughts can have an adverse effect on COPD outcomes.
Disease-related mental distress can lead to increased disability, more frequent use of costly health care resources, higher morbidity, and elevated risk of death, investigators say.
"Individuals with severe COPD are twice as likely to develop depression than patients with mild COPD. Prevalence rates for clinical anxiety in COPD range from 13% to 46% in outpatients and 10% to 55% among inpatients," wrote Abebaw Mengitsu Yohannes, PhD, then from Azusa Pacific University in Azusa, California and colleagues in an article published jointly by The Journal of Family Practice and The Cleveland Clinic Journal of Medicine.
Patients with COPD may experience major depressive disorders, chronic mild depression (dysthymias), and minor depression, as well as generalized anxiety disorder, phobias, and panic disorders, the investigators say.
"Growing evidence suggests that the relationship between mood disorders, particularly depression, and COPD is bidirectional, meaning that mood disorders adversely impact prognosis in COPD, whereas COPD increases the risk of developing depression," Yohannes et al wrote.
Jamie Garfield, MD, professor of thoracic medicine and surgery at Temple University's Lewis Katz School of Medicine in Philadelphia, told Chest Physician that the association between severe chronic diseases and mood disorders is well known.
"I don't think that it's specific to chronic lung diseases; in people with chronic heart disease or malignancies we see that co-existence of depression and anxiety will worsen the course of disease," she said.
Dr. Johannes, who is currently a professor of physical therapy at the University of Alabama School of Health Professionals in Birmingham, said that depression and anxiety are often underdiagnosed and undertreated in patients with obstructive pulmonary diseases because the conditions can share symptoms such as dyspnea (for example, in anxiety) or fatigue (in depression).
"Therefore, unless one begins to explore further, it's hard for physicians to be able to identify these conditions," he said in an interview with Chest Physician.
Fears of dying (and living)
The causes of depression and anxiety among patients with obstructive pulmonary disorders are multi-factorial, and may require a variety of treatment and coping strategies, according to Susann Strang, RN, PhD, and colleagues from the University of Gothenburg, Sweden.
They conducted qualitative in-depth interviews with 31 men and women with stage III or IV COPD, and found that the majority of patients had anxiety associated with their disease.
"Analyses revealed three major themes: death anxiety, life anxiety, and counterweights to anxiety," the investigators wrote in a study published in the journal Palliative and Supportive Care in 2014.
Factors contributing to anxiety surrounding death included fear of suffocation, awareness of impending death, fear of the process of death, and anxiety about being separated from loved ones.
In contrast, some patients expressed dread of living with the limitations and loneliness imposed on them by their disease, so called "life anxiety."
The patients also reported "counterweights" to anxiety as a way of coping. For some this involved trust in their health care professionals and adherence to medication, inhalers, and supplemental oxygen.
"The patients also placed hope in new treatments, better medication, surgery, stem cell treatment, or lung transplants," Dr. Strang and colleagues reported.
Others reported avoiding talking about death, sleeping more, or using humor to "laugh off this difficult subject."
Screening and diagnosis
Primary care practitioners are often the first health professionals that patients with COPD see, but these clinicians often don't have the time to add screening to their already crammed schedules. In addition, "the lack of a standardized approach in diagnosis, and inadequate knowledge or confidence in assessing psychological status (particularly given the number of strategies available for screening patients for mood disorders)," can make it difficult for PCPs to detect and manage anxiety and depression in their patients with significant health care burdens from COPD and other obstructive lung diseases, Dr. Yohannes and colleagues noted.
In addition to commonly used screening tools for anxiety and depression such as the Primary Care Evaluation of Mental Disorders (PRIME-MD) Patient Health Questionnaire (PHQ-9), there are at least two designed to evaluate patients with lung disease: the Anxiety Inventory for Respiratory (AIR) Disease scale, developed by Dr. Johannes and colleagues, and the COPD Anxiety Questionnaire.
The COPD Assessment Testand Clinical COPD Questionnaire, while not specifically designed to screen for mental disorders, include questions that can point to symptoms of distress in patients with COPD, Dr. Yohannes said.
"In truth I think that there are few providers who will routinely do this on all their patients in terms of quantifying the severity or the presence or absence of depression, but in my own practice I very much ask questions that align with the questions in these tools to determine whether my patient appears to have high levels of anxiety and depression," Dr. Garfield said.
Listen to patients and families
Among the most powerful tools that clinicians have at their disposal for treating anxiety and depression in patients with chronic lung disease are their ears and their minds, said Anthony Saleh, MD, a pulmonologist at New York-Presbyterian Brooklyn Methodist Hospital in Brooklyn, New York.
"I think just listening to the patient, that's a little bit forgotten yet so important," he said in an interview with Chest Physician.
"When I have someone with advanced lung disease, like idiopathic pulmonary fibrosis, like advanced emphysema, one of the most important things I think is to listen to the patient, and not just to listen to the answers of your perfunctory 'how's your breathing? Any chest pain?' and those sort of rote medical questions, but listen to their thoughts, and it will given them a safe space to say 'Hey, I'm nervous, hey I'm worried about my family, hey I'm worried if I die what's going to happen to my wife and kids,' and that's something I think is invaluable."
It's also vital to listen to the concerns of the patients family members, who may be the primary caregivers and may share the patient's stresses and anxieties, he said.
Pulmonary Rehabilitation
All of the experts interviewed for this article agreed that a combination of medical, social and mental health support services is important for treatment for patients with chronic obstructive lung diseases.
One of the most effective means of helping patients with both acute breathing problems and with disease-related anxiety and depression is pulmonary rehabilitation. Depending on disease severity, this multidisciplinary approach may involve exercise, patient education, psychological and nutrition counseling, and training patients how to conserve energy and adopt breathing strategies to help them better manage their symptoms.
"I think that pulmonary rehabilitation is one of the first interventions that we should be recommending for our patients," Dr. Garfield said. "It's physical therapy for patients with chronic lung diseases, backed by respiratory therapists, and it offers not only physical rehabilitation - improving strength and coordination, but also it helps our patients get as much as possible out of what they've got."
For example, patients can be taught how to decrease their respiratory rate when they're feeling a sense of urgency or panic. Patients can also learn how to change body positions to help them breathe more effectively when they feel that their breath is limited or restricted, she said.
"Once your into medical interventions, pulmonary rehab is phenomenal," Dr. Saleh said.
Pulmonary rehabilitation helps patients to feel better about themselves and about their abilities, but "unfortunately it's not as available as we like," he said.
Many patients don't live near a pulmonary rehabilitation center, and the typical two to three weekly sessions for 4 to 12 weeks or longer can be a significant burden for patients and caregivers, he acknowledged.
"You have to sit [with the patient] and be honest and tell them it's a lot of diligence involved and you have to be really motivated," he said.
Other treatment options include pharmacological therapy with antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and anxiolytic agents.
"SSRIs are the current first-line drug treatment for depression, and have been shown to significantly improve depression and anxiety in patients with COPD in some, but not all, trials published to date. However, it is important to note that a diagnosis of bipolar disorder must be ruled out before initiating standard antidepressant therapy," Dr. Johannes and colleagues wrote.
Defiant joy
Importantly, even with the burden of life with COPD, many patients found ways to experience what Strang et al called "a defiant joy."
"It was remarkable that when the patients were asked about what gave their lives meaning today, many talked about what had given their life meaning in the past, prior to becoming ill. In the light of the things they had lost because of the disease, many felt that their previous sources of joy no longer existed. Despite this, many still hoped to be able to get out into the fresh air, to be able to do errands or that tomorrow might be better," the investigators wrote.
Dr. Yohannes, Dr. Garfield, and Dr. Saleh all reported having no relevant conflicts of interest to report.
Many patients with chronic progressive pulmonary disease feel anxious and depressed as their conditions advance, as breathing becomes increasingly labored and difficult, and as performing even small daily tasks leaves them exhausted.
Persons with severe COPD frequently report fears of suffocation and death, as well as anxieties about abandoning family and friends, and these negative, intrusive thoughts can have an adverse effect on COPD outcomes.
Disease-related mental distress can lead to increased disability, more frequent use of costly health care resources, higher morbidity, and elevated risk of death, investigators say.
"Individuals with severe COPD are twice as likely to develop depression than patients with mild COPD. Prevalence rates for clinical anxiety in COPD range from 13% to 46% in outpatients and 10% to 55% among inpatients," wrote Abebaw Mengitsu Yohannes, PhD, then from Azusa Pacific University in Azusa, California and colleagues in an article published jointly by The Journal of Family Practice and The Cleveland Clinic Journal of Medicine.
Patients with COPD may experience major depressive disorders, chronic mild depression (dysthymias), and minor depression, as well as generalized anxiety disorder, phobias, and panic disorders, the investigators say.
"Growing evidence suggests that the relationship between mood disorders, particularly depression, and COPD is bidirectional, meaning that mood disorders adversely impact prognosis in COPD, whereas COPD increases the risk of developing depression," Yohannes et al wrote.
Jamie Garfield, MD, professor of thoracic medicine and surgery at Temple University's Lewis Katz School of Medicine in Philadelphia, told Chest Physician that the association between severe chronic diseases and mood disorders is well known.
"I don't think that it's specific to chronic lung diseases; in people with chronic heart disease or malignancies we see that co-existence of depression and anxiety will worsen the course of disease," she said.
Dr. Johannes, who is currently a professor of physical therapy at the University of Alabama School of Health Professionals in Birmingham, said that depression and anxiety are often underdiagnosed and undertreated in patients with obstructive pulmonary diseases because the conditions can share symptoms such as dyspnea (for example, in anxiety) or fatigue (in depression).
"Therefore, unless one begins to explore further, it's hard for physicians to be able to identify these conditions," he said in an interview with Chest Physician.
Fears of dying (and living)
The causes of depression and anxiety among patients with obstructive pulmonary disorders are multi-factorial, and may require a variety of treatment and coping strategies, according to Susann Strang, RN, PhD, and colleagues from the University of Gothenburg, Sweden.
They conducted qualitative in-depth interviews with 31 men and women with stage III or IV COPD, and found that the majority of patients had anxiety associated with their disease.
"Analyses revealed three major themes: death anxiety, life anxiety, and counterweights to anxiety," the investigators wrote in a study published in the journal Palliative and Supportive Care in 2014.
Factors contributing to anxiety surrounding death included fear of suffocation, awareness of impending death, fear of the process of death, and anxiety about being separated from loved ones.
In contrast, some patients expressed dread of living with the limitations and loneliness imposed on them by their disease, so called "life anxiety."
The patients also reported "counterweights" to anxiety as a way of coping. For some this involved trust in their health care professionals and adherence to medication, inhalers, and supplemental oxygen.
"The patients also placed hope in new treatments, better medication, surgery, stem cell treatment, or lung transplants," Dr. Strang and colleagues reported.
Others reported avoiding talking about death, sleeping more, or using humor to "laugh off this difficult subject."
Screening and diagnosis
Primary care practitioners are often the first health professionals that patients with COPD see, but these clinicians often don't have the time to add screening to their already crammed schedules. In addition, "the lack of a standardized approach in diagnosis, and inadequate knowledge or confidence in assessing psychological status (particularly given the number of strategies available for screening patients for mood disorders)," can make it difficult for PCPs to detect and manage anxiety and depression in their patients with significant health care burdens from COPD and other obstructive lung diseases, Dr. Yohannes and colleagues noted.
In addition to commonly used screening tools for anxiety and depression such as the Primary Care Evaluation of Mental Disorders (PRIME-MD) Patient Health Questionnaire (PHQ-9), there are at least two designed to evaluate patients with lung disease: the Anxiety Inventory for Respiratory (AIR) Disease scale, developed by Dr. Johannes and colleagues, and the COPD Anxiety Questionnaire.
The COPD Assessment Testand Clinical COPD Questionnaire, while not specifically designed to screen for mental disorders, include questions that can point to symptoms of distress in patients with COPD, Dr. Yohannes said.
"In truth I think that there are few providers who will routinely do this on all their patients in terms of quantifying the severity or the presence or absence of depression, but in my own practice I very much ask questions that align with the questions in these tools to determine whether my patient appears to have high levels of anxiety and depression," Dr. Garfield said.
Listen to patients and families
Among the most powerful tools that clinicians have at their disposal for treating anxiety and depression in patients with chronic lung disease are their ears and their minds, said Anthony Saleh, MD, a pulmonologist at New York-Presbyterian Brooklyn Methodist Hospital in Brooklyn, New York.
"I think just listening to the patient, that's a little bit forgotten yet so important," he said in an interview with Chest Physician.
"When I have someone with advanced lung disease, like idiopathic pulmonary fibrosis, like advanced emphysema, one of the most important things I think is to listen to the patient, and not just to listen to the answers of your perfunctory 'how's your breathing? Any chest pain?' and those sort of rote medical questions, but listen to their thoughts, and it will given them a safe space to say 'Hey, I'm nervous, hey I'm worried about my family, hey I'm worried if I die what's going to happen to my wife and kids,' and that's something I think is invaluable."
It's also vital to listen to the concerns of the patients family members, who may be the primary caregivers and may share the patient's stresses and anxieties, he said.
Pulmonary Rehabilitation
All of the experts interviewed for this article agreed that a combination of medical, social and mental health support services is important for treatment for patients with chronic obstructive lung diseases.
One of the most effective means of helping patients with both acute breathing problems and with disease-related anxiety and depression is pulmonary rehabilitation. Depending on disease severity, this multidisciplinary approach may involve exercise, patient education, psychological and nutrition counseling, and training patients how to conserve energy and adopt breathing strategies to help them better manage their symptoms.
"I think that pulmonary rehabilitation is one of the first interventions that we should be recommending for our patients," Dr. Garfield said. "It's physical therapy for patients with chronic lung diseases, backed by respiratory therapists, and it offers not only physical rehabilitation - improving strength and coordination, but also it helps our patients get as much as possible out of what they've got."
For example, patients can be taught how to decrease their respiratory rate when they're feeling a sense of urgency or panic. Patients can also learn how to change body positions to help them breathe more effectively when they feel that their breath is limited or restricted, she said.
"Once your into medical interventions, pulmonary rehab is phenomenal," Dr. Saleh said.
Pulmonary rehabilitation helps patients to feel better about themselves and about their abilities, but "unfortunately it's not as available as we like," he said.
Many patients don't live near a pulmonary rehabilitation center, and the typical two to three weekly sessions for 4 to 12 weeks or longer can be a significant burden for patients and caregivers, he acknowledged.
"You have to sit [with the patient] and be honest and tell them it's a lot of diligence involved and you have to be really motivated," he said.
Other treatment options include pharmacological therapy with antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and anxiolytic agents.
"SSRIs are the current first-line drug treatment for depression, and have been shown to significantly improve depression and anxiety in patients with COPD in some, but not all, trials published to date. However, it is important to note that a diagnosis of bipolar disorder must be ruled out before initiating standard antidepressant therapy," Dr. Johannes and colleagues wrote.
Defiant joy
Importantly, even with the burden of life with COPD, many patients found ways to experience what Strang et al called "a defiant joy."
"It was remarkable that when the patients were asked about what gave their lives meaning today, many talked about what had given their life meaning in the past, prior to becoming ill. In the light of the things they had lost because of the disease, many felt that their previous sources of joy no longer existed. Despite this, many still hoped to be able to get out into the fresh air, to be able to do errands or that tomorrow might be better," the investigators wrote.
Dr. Yohannes, Dr. Garfield, and Dr. Saleh all reported having no relevant conflicts of interest to report.
FDA Removes Harmful Chemicals From Food Packaging
Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.
In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.
PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
Endocrine Society Report Sounds the Alarm About PFAS and Others
The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.
“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.
The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.
At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”
Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”
While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.
Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.
Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.
“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
New Data on Four Classes of EDCs
Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.
The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.
Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.
Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.
The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’
Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.
The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”
The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.
A version of this article appeared on Medscape.com.
Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.
In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.
PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
Endocrine Society Report Sounds the Alarm About PFAS and Others
The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.
“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.
The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.
At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”
Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”
While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.
Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.
Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.
“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
New Data on Four Classes of EDCs
Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.
The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.
Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.
Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.
The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’
Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.
The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”
The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.
A version of this article appeared on Medscape.com.
Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.
In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.
PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
Endocrine Society Report Sounds the Alarm About PFAS and Others
The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.
“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.
The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.
At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”
Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”
While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.
Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.
Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.
“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
New Data on Four Classes of EDCs
Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.
The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.
Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.
Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.
The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’
Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.
The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”
The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.
A version of this article appeared on Medscape.com.
Biological Sex Differences: Key to Understanding Long COVID?
Letícia Soares was infected with COVID-19 in April 2020, in the final year of postdoctoral studies in disease ecology at a Canadian University. What started with piercing migraines and severe fatigue in 2020 soon spiraled into a myriad of long COVID symptoms: Gastrointestinal issues, sleep problems, joint and muscle pain, along with unexpected menstrual changes.
After an absence of menstrual bleeding and its usual signs, she later suffered from severe periods and symptoms that worsened her long COVID condition. “It just baffled me,” said Soares, now 39. “It was debilitating.”
Cases like Soares’s are leading scientists to spend more time trying to understand the biological sex disparity in chronic illnesses such as long COVID that until recently have all but been ignored. According to the Centers for Disease Control and Prevention, long COVID affects nearly twice as many women as men.
What’s more, up to two thirds of female patients with long COVID report an increase in symptoms related to menstruation, which suggests a possible link between sex hormone fluctuations and immune dysfunction in the illness.
“These illnesses are underfunded and understudied relative to their disease burdens,” said Beth Pollack, a research scientist at the Massachusetts Institute of Technology, Cambridge, Massachusetts, who studies complex chronic illnesses.
Addressing knowledge gaps, especially around sex differences, could significantly improve our understanding of complex chronic illnesses, said Pollack, who coauthored a 2023 literature review of female reproductive health impacts of long COVID.
Emerging ‘Menstrual Science’ Could Be Key
There is a critical need, she said, for studies on these illnesses to include considerations of sex differences, hormones, reproductive phases, and reproductive conditions. This research could potentially inform doctors and other clinicians or lead to treatments, both for reproductive symptoms and for the illnesses themselves.
Pollack noted that reproductive symptoms are prevalent across a group of infection-associated chronic illnesses she studies, all of which disproportionately affect women. These associated conditions, traditionally studied in isolation, share pathologies like reproductive health concerns, signaling a need for focused research on their shared mechanisms.
Recognizing this critical gap, “menstrual science” is emerging as a pivotal area of study, aiming to connect these dots through focused research on hormonal influences.
Researchers at the University of Melbourne, Melbourne, Australia, for example, are studying whether hormones play a role in causing or worsening the symptoms of long COVID. By comparing hormone levels in people with these conditions with those in healthy people and by tracking how symptoms change with hormone levels over time and across menstrual cycles, scientists hope to find patterns that could help diagnose these conditions more easily and lead to new treatments. They’re also examining how hormonal life phases such as puberty, pregnancy, or perimenopause and hormone treatments like birth control might affect these illnesses.
How Gender and Long COVID Intertwine
The pathologies of long COVID, affecting at least 65 million people worldwide, currently focus on four hypotheses: Persistent viral infection, reactivation of dormant viruses (such as common herpes viruses), inflammation-related damage to tissues and organs, and autoimmunity (the body attacking itself).
It’s this last reason that holds some of the most interesting clues on biological sex differences, said Akiko Iwasaki, PhD, a Yale University, New Haven, Connecticut, immunologist who has led numerous research breakthroughs on long COVID since the start of the pandemic. Women have two X chromosomes, for example, and although one is inactivated, the inactivation is incomplete.
Some cells still express genes from the “inactivated genes” on the X chromosome, Iwasaki said. Those include key immune genes, which trigger a more robust response to infections and vaccinations but also predispose them to autoimmune reactions. “It comes at the cost of triggering too much immune response,” Iwasaki said.
Sex hormones also factor in. Testosterone, which is higher in males, is immunosuppressive, so it can dampen immune responses, Iwasaki said. That may contribute to making males more likely to get severe acute infections of COVID-19 but have fewer long-term effects.
Estrogen, on the other hand, is known to enhance the immune response. It can increase the production of antibodies and the activation of T cells, which are critical for fighting off infections. This heightened immune response, however, might also contribute to the persistent inflammation observed in long COVID, where the immune system continues to react even after the acute infection has resolved.
Sex-Specific Symptoms and Marginalized Communities
Of the more than 200 symptoms long haulers experience, Iwasaki said, several are also sex-specific. A recent draft study by Iwasaki and another leading COVID researcher, David Putrino, PhD, at Mount Sinai Health System in New York City, shows hair loss as one of the most female-dominant symptoms and sexual dysfunction among males.
In examining sex differences, another question is why long COVID rates in the trans community are disproportionately high. One of the reasons Iwasaki’s lab is looking at testosterone closely is because anecdotal evidence from female-to-male trans individuals indicates that testosterone therapy improved their long COVID symptoms significantly. It also raises the possibility that hormone therapy could help.
However, patients and advocates say it’s also important to consider socioeconomic factors in the trans community. “We need to start at this population and social structure level to understand why trans people over and over are put in harm’s way,” said JD Davids, a trans patient-researcher with long COVID and the cofounder and codirector of Strategies for High Impact and its Long COVID Justice project.
For trans people, said Davids, risk factors for both severe COVID and long COVID include being part of low-income groups, belonging to marginalized racial and ethnic communities, and living in crowded environments such as shelters or prisons.
The disproportionate impact of long COVID on marginalized communities, especially when seen through the lens of historical medical neglect, also demands attention, said Iwasaki. “Women used to be labeled hysteric when they complained about these kinds of symptoms.”
Where It All Leads
The possibility of diagnosing long COVID with a simple blood test could radically change some doctors’ false perceptions that it is not a real condition, Iwasaki said, ensuring it is recognized and treated with the seriousness it deserves.
“I feel like we need to get there with long COVID. If we can order a blood test and say somebody has a long COVID because of these values, then suddenly the diseases become medically explainable,” Iwasaki added. This advancement is critical for propelling research forward, she said, refining treatment approaches — including those that target sex-specific hormone, immunity, and inflammation issues — and improving the well-being of those living with long COVID.
This hope resonates with scientists like Pollack, who recently led the first National Institutes of Health-sponsored research webinar on less studied pathologies in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID, and with the experiences of individuals like Soares, who navigates through the unpredictable nature of both of these conditions with resilience.
“This illness never ceases to surprise me in how it changes my body. I feel like it’s a constant adaptation,” said Soares. Now living in Salvador, Brazil, her daily life has dramatically shifted to the confines of her home.
“It’s how I have more predictability in my symptoms,” she said, pointing out the pressing need for the scientific advancements that Iwasaki envisions and a deepening of our understanding of the disease’s impacts on patients’ lives.
A version of this article appeared on Medscape.com.
Letícia Soares was infected with COVID-19 in April 2020, in the final year of postdoctoral studies in disease ecology at a Canadian University. What started with piercing migraines and severe fatigue in 2020 soon spiraled into a myriad of long COVID symptoms: Gastrointestinal issues, sleep problems, joint and muscle pain, along with unexpected menstrual changes.
After an absence of menstrual bleeding and its usual signs, she later suffered from severe periods and symptoms that worsened her long COVID condition. “It just baffled me,” said Soares, now 39. “It was debilitating.”
Cases like Soares’s are leading scientists to spend more time trying to understand the biological sex disparity in chronic illnesses such as long COVID that until recently have all but been ignored. According to the Centers for Disease Control and Prevention, long COVID affects nearly twice as many women as men.
What’s more, up to two thirds of female patients with long COVID report an increase in symptoms related to menstruation, which suggests a possible link between sex hormone fluctuations and immune dysfunction in the illness.
“These illnesses are underfunded and understudied relative to their disease burdens,” said Beth Pollack, a research scientist at the Massachusetts Institute of Technology, Cambridge, Massachusetts, who studies complex chronic illnesses.
Addressing knowledge gaps, especially around sex differences, could significantly improve our understanding of complex chronic illnesses, said Pollack, who coauthored a 2023 literature review of female reproductive health impacts of long COVID.
Emerging ‘Menstrual Science’ Could Be Key
There is a critical need, she said, for studies on these illnesses to include considerations of sex differences, hormones, reproductive phases, and reproductive conditions. This research could potentially inform doctors and other clinicians or lead to treatments, both for reproductive symptoms and for the illnesses themselves.
Pollack noted that reproductive symptoms are prevalent across a group of infection-associated chronic illnesses she studies, all of which disproportionately affect women. These associated conditions, traditionally studied in isolation, share pathologies like reproductive health concerns, signaling a need for focused research on their shared mechanisms.
Recognizing this critical gap, “menstrual science” is emerging as a pivotal area of study, aiming to connect these dots through focused research on hormonal influences.
Researchers at the University of Melbourne, Melbourne, Australia, for example, are studying whether hormones play a role in causing or worsening the symptoms of long COVID. By comparing hormone levels in people with these conditions with those in healthy people and by tracking how symptoms change with hormone levels over time and across menstrual cycles, scientists hope to find patterns that could help diagnose these conditions more easily and lead to new treatments. They’re also examining how hormonal life phases such as puberty, pregnancy, or perimenopause and hormone treatments like birth control might affect these illnesses.
How Gender and Long COVID Intertwine
The pathologies of long COVID, affecting at least 65 million people worldwide, currently focus on four hypotheses: Persistent viral infection, reactivation of dormant viruses (such as common herpes viruses), inflammation-related damage to tissues and organs, and autoimmunity (the body attacking itself).
It’s this last reason that holds some of the most interesting clues on biological sex differences, said Akiko Iwasaki, PhD, a Yale University, New Haven, Connecticut, immunologist who has led numerous research breakthroughs on long COVID since the start of the pandemic. Women have two X chromosomes, for example, and although one is inactivated, the inactivation is incomplete.
Some cells still express genes from the “inactivated genes” on the X chromosome, Iwasaki said. Those include key immune genes, which trigger a more robust response to infections and vaccinations but also predispose them to autoimmune reactions. “It comes at the cost of triggering too much immune response,” Iwasaki said.
Sex hormones also factor in. Testosterone, which is higher in males, is immunosuppressive, so it can dampen immune responses, Iwasaki said. That may contribute to making males more likely to get severe acute infections of COVID-19 but have fewer long-term effects.
Estrogen, on the other hand, is known to enhance the immune response. It can increase the production of antibodies and the activation of T cells, which are critical for fighting off infections. This heightened immune response, however, might also contribute to the persistent inflammation observed in long COVID, where the immune system continues to react even after the acute infection has resolved.
Sex-Specific Symptoms and Marginalized Communities
Of the more than 200 symptoms long haulers experience, Iwasaki said, several are also sex-specific. A recent draft study by Iwasaki and another leading COVID researcher, David Putrino, PhD, at Mount Sinai Health System in New York City, shows hair loss as one of the most female-dominant symptoms and sexual dysfunction among males.
In examining sex differences, another question is why long COVID rates in the trans community are disproportionately high. One of the reasons Iwasaki’s lab is looking at testosterone closely is because anecdotal evidence from female-to-male trans individuals indicates that testosterone therapy improved their long COVID symptoms significantly. It also raises the possibility that hormone therapy could help.
However, patients and advocates say it’s also important to consider socioeconomic factors in the trans community. “We need to start at this population and social structure level to understand why trans people over and over are put in harm’s way,” said JD Davids, a trans patient-researcher with long COVID and the cofounder and codirector of Strategies for High Impact and its Long COVID Justice project.
For trans people, said Davids, risk factors for both severe COVID and long COVID include being part of low-income groups, belonging to marginalized racial and ethnic communities, and living in crowded environments such as shelters or prisons.
The disproportionate impact of long COVID on marginalized communities, especially when seen through the lens of historical medical neglect, also demands attention, said Iwasaki. “Women used to be labeled hysteric when they complained about these kinds of symptoms.”
Where It All Leads
The possibility of diagnosing long COVID with a simple blood test could radically change some doctors’ false perceptions that it is not a real condition, Iwasaki said, ensuring it is recognized and treated with the seriousness it deserves.
“I feel like we need to get there with long COVID. If we can order a blood test and say somebody has a long COVID because of these values, then suddenly the diseases become medically explainable,” Iwasaki added. This advancement is critical for propelling research forward, she said, refining treatment approaches — including those that target sex-specific hormone, immunity, and inflammation issues — and improving the well-being of those living with long COVID.
This hope resonates with scientists like Pollack, who recently led the first National Institutes of Health-sponsored research webinar on less studied pathologies in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID, and with the experiences of individuals like Soares, who navigates through the unpredictable nature of both of these conditions with resilience.
“This illness never ceases to surprise me in how it changes my body. I feel like it’s a constant adaptation,” said Soares. Now living in Salvador, Brazil, her daily life has dramatically shifted to the confines of her home.
“It’s how I have more predictability in my symptoms,” she said, pointing out the pressing need for the scientific advancements that Iwasaki envisions and a deepening of our understanding of the disease’s impacts on patients’ lives.
A version of this article appeared on Medscape.com.
Letícia Soares was infected with COVID-19 in April 2020, in the final year of postdoctoral studies in disease ecology at a Canadian University. What started with piercing migraines and severe fatigue in 2020 soon spiraled into a myriad of long COVID symptoms: Gastrointestinal issues, sleep problems, joint and muscle pain, along with unexpected menstrual changes.
After an absence of menstrual bleeding and its usual signs, she later suffered from severe periods and symptoms that worsened her long COVID condition. “It just baffled me,” said Soares, now 39. “It was debilitating.”
Cases like Soares’s are leading scientists to spend more time trying to understand the biological sex disparity in chronic illnesses such as long COVID that until recently have all but been ignored. According to the Centers for Disease Control and Prevention, long COVID affects nearly twice as many women as men.
What’s more, up to two thirds of female patients with long COVID report an increase in symptoms related to menstruation, which suggests a possible link between sex hormone fluctuations and immune dysfunction in the illness.
“These illnesses are underfunded and understudied relative to their disease burdens,” said Beth Pollack, a research scientist at the Massachusetts Institute of Technology, Cambridge, Massachusetts, who studies complex chronic illnesses.
Addressing knowledge gaps, especially around sex differences, could significantly improve our understanding of complex chronic illnesses, said Pollack, who coauthored a 2023 literature review of female reproductive health impacts of long COVID.
Emerging ‘Menstrual Science’ Could Be Key
There is a critical need, she said, for studies on these illnesses to include considerations of sex differences, hormones, reproductive phases, and reproductive conditions. This research could potentially inform doctors and other clinicians or lead to treatments, both for reproductive symptoms and for the illnesses themselves.
Pollack noted that reproductive symptoms are prevalent across a group of infection-associated chronic illnesses she studies, all of which disproportionately affect women. These associated conditions, traditionally studied in isolation, share pathologies like reproductive health concerns, signaling a need for focused research on their shared mechanisms.
Recognizing this critical gap, “menstrual science” is emerging as a pivotal area of study, aiming to connect these dots through focused research on hormonal influences.
Researchers at the University of Melbourne, Melbourne, Australia, for example, are studying whether hormones play a role in causing or worsening the symptoms of long COVID. By comparing hormone levels in people with these conditions with those in healthy people and by tracking how symptoms change with hormone levels over time and across menstrual cycles, scientists hope to find patterns that could help diagnose these conditions more easily and lead to new treatments. They’re also examining how hormonal life phases such as puberty, pregnancy, or perimenopause and hormone treatments like birth control might affect these illnesses.
How Gender and Long COVID Intertwine
The pathologies of long COVID, affecting at least 65 million people worldwide, currently focus on four hypotheses: Persistent viral infection, reactivation of dormant viruses (such as common herpes viruses), inflammation-related damage to tissues and organs, and autoimmunity (the body attacking itself).
It’s this last reason that holds some of the most interesting clues on biological sex differences, said Akiko Iwasaki, PhD, a Yale University, New Haven, Connecticut, immunologist who has led numerous research breakthroughs on long COVID since the start of the pandemic. Women have two X chromosomes, for example, and although one is inactivated, the inactivation is incomplete.
Some cells still express genes from the “inactivated genes” on the X chromosome, Iwasaki said. Those include key immune genes, which trigger a more robust response to infections and vaccinations but also predispose them to autoimmune reactions. “It comes at the cost of triggering too much immune response,” Iwasaki said.
Sex hormones also factor in. Testosterone, which is higher in males, is immunosuppressive, so it can dampen immune responses, Iwasaki said. That may contribute to making males more likely to get severe acute infections of COVID-19 but have fewer long-term effects.
Estrogen, on the other hand, is known to enhance the immune response. It can increase the production of antibodies and the activation of T cells, which are critical for fighting off infections. This heightened immune response, however, might also contribute to the persistent inflammation observed in long COVID, where the immune system continues to react even after the acute infection has resolved.
Sex-Specific Symptoms and Marginalized Communities
Of the more than 200 symptoms long haulers experience, Iwasaki said, several are also sex-specific. A recent draft study by Iwasaki and another leading COVID researcher, David Putrino, PhD, at Mount Sinai Health System in New York City, shows hair loss as one of the most female-dominant symptoms and sexual dysfunction among males.
In examining sex differences, another question is why long COVID rates in the trans community are disproportionately high. One of the reasons Iwasaki’s lab is looking at testosterone closely is because anecdotal evidence from female-to-male trans individuals indicates that testosterone therapy improved their long COVID symptoms significantly. It also raises the possibility that hormone therapy could help.
However, patients and advocates say it’s also important to consider socioeconomic factors in the trans community. “We need to start at this population and social structure level to understand why trans people over and over are put in harm’s way,” said JD Davids, a trans patient-researcher with long COVID and the cofounder and codirector of Strategies for High Impact and its Long COVID Justice project.
For trans people, said Davids, risk factors for both severe COVID and long COVID include being part of low-income groups, belonging to marginalized racial and ethnic communities, and living in crowded environments such as shelters or prisons.
The disproportionate impact of long COVID on marginalized communities, especially when seen through the lens of historical medical neglect, also demands attention, said Iwasaki. “Women used to be labeled hysteric when they complained about these kinds of symptoms.”
Where It All Leads
The possibility of diagnosing long COVID with a simple blood test could radically change some doctors’ false perceptions that it is not a real condition, Iwasaki said, ensuring it is recognized and treated with the seriousness it deserves.
“I feel like we need to get there with long COVID. If we can order a blood test and say somebody has a long COVID because of these values, then suddenly the diseases become medically explainable,” Iwasaki added. This advancement is critical for propelling research forward, she said, refining treatment approaches — including those that target sex-specific hormone, immunity, and inflammation issues — and improving the well-being of those living with long COVID.
This hope resonates with scientists like Pollack, who recently led the first National Institutes of Health-sponsored research webinar on less studied pathologies in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID, and with the experiences of individuals like Soares, who navigates through the unpredictable nature of both of these conditions with resilience.
“This illness never ceases to surprise me in how it changes my body. I feel like it’s a constant adaptation,” said Soares. Now living in Salvador, Brazil, her daily life has dramatically shifted to the confines of her home.
“It’s how I have more predictability in my symptoms,” she said, pointing out the pressing need for the scientific advancements that Iwasaki envisions and a deepening of our understanding of the disease’s impacts on patients’ lives.
A version of this article appeared on Medscape.com.
‘There’s Nothing Left to Try’: Oncologists on Managing Grief
Dr. Lewis was well acquainted with cancer grief long before he became an oncologist. Dr. Lewis’ father died of a rare, hereditary cancer syndrome when he was only 14. The condition, which causes tumors to grow in the endocrine glands, can be hard to identify and, if found late, deadly.
In some ways, Dr. Lewis’ career caring for patients with advanced cancers was born out of that first loss. He centered his practice around helping patients diagnosed at late stages, like his father.
But that comes at a cost. Many patients will die.
Dr. Lewis’ encounter with his colleague led him to inventory his practice. He found that well over half of his patients died within 2 years following their advanced cancer diagnosis.
To stave off the grief of so many losses, Dr. Lewis became an eternal optimist in the clinic, in search of the Hail Mary chemotherapy, any way to eke out a few more months only to be ambushed by grief when a patient did finally pass.
At funerals — which he made every effort to attend — Dr. Lewis couldn’t help but think, “If I had done my job better, none of us with be here.” His grief started to mingle with this sense of guilt.
It became a cycle: Denial shrouded in optimism, grief, then a toxic guilt. The pattern became untenable for his colleagues. And his partner finally called him out.
Few medical specialties draw physicians as close to their patients as oncology. The long courses of treatment-spanning years can foster an intimacy that is comforting for patients and fulfilling for physicians. But that closeness can also set doctors up for an acute grief when the end of life comes.
Experts agree that no amount of training in medical school prepares an oncologist to navigate the grief that comes with losing patients. Five oncologists spoke with this news organization about the boundaries they rely on to sustain their careers.
Don’t Go to Funerals
Don Dizon, MD, who specializes in women’s cancers, established an essential boundary 20 years ago: Never go to funerals. In his early days at Memorial Sloan Kettering Cancer Center, the death of each patient dealt him a crushing blow. He’d go to the funerals in search of closure, but that only added to the weight of his grief.
“When I started in oncology, I just remember the most tragic cases were the ones I was taking care of,” recalled Dr. Dizon, now director of the Pelvic Malignancies Program at Lifespan Cancer Institute in Lincoln, Rhode Island.
Dr. Dizon recalled one young mother who was diagnosed with ovarian cancer. She responded to treatment, but it was short-lived, and her cancer progressed, he said. Multiple treatments followed, but none were effective. Eventually, Dr. Dizon had to tell her that “there’s nothing left to try.”
At her funeral, watching her grieving husband with their daughter who had just started to walk, Dr. Dizon was overwhelmed with despair.
“When you have to do this multiple times a year,” the grief becomes untenable, he said. Sensing the difficulty I was having as a new attending, “my boss stopped sending me patients because he knew I was in trouble emotionally.”
That’s when Dr. Dizon started looking for other ways to get closure.
Today, he tries to say his goodbyes before a patient dies. After the final treatment or before hospice, Dr. Dizon has a parting conversation with his patients to express the privilege of caring for them and all he learned from them. These talks help him and his patient connect in their last moments together.
The Price of Wildly Happy Days
Molly Taylor, MD, MS, a pediatric oncologist in Seattle, sees the deeply sad days as the price an oncologist pays to be witness to the “wildly happy ones.”
Dr. Taylor has gone to patients’ funerals, has even been asked to speak at them, but she has also attended patients’ weddings.
To some degree, doctors get good at compartmentalizing, and they become accustomed to tragedy, she said. But there are some patients who stick with you, “and that is a whole other level of grief,” Dr. Taylor said.
Several years into her practice, one of Dr. Taylor’s patients, someone who reminded her of her own child, died. The death came as a surprise, and the finality of it took her breath away, she said. The sadness only deepened as days went by. “I felt that mother’s grief and still do,” she said.
The patient’s funeral was one of the most difficult moments in her career as an oncologist. Even weeks later, she caught herself picturing the family huddled together that day.
Taking long walks, commiserating with colleagues who get it, and watching the occasional cat video can help take the immediate sting away. But the pain of losing a patient can be long lasting and processing that grief can be a lonely endeavor.
“We need space to recognize grief for all providers, all the people that touch these patients’ lives — the nurses, the translators, the cleaning staff,” Dr. Taylor said. Otherwise, you start to believe you’re the only one feeling the weight of the loss.
While it doesn’t make the losses any less poignant, Dr. Taylor finds solace in the good moments: Patient graduations and weddings, survivors who now volunteer at the hospital, and a patient who had a baby of her own this past year. If facing grief daily has taught Dr. Taylor anything, it is to not let the good moments pass unnoticed.
Towing the Line
Ten years ago, Tina Rizack, MD, walked into the ICU to see a young mother holding her 6-year-old daughter. The mother had necrotizing fasciitis that had gone undiagnosed.
As Dr. Rizack stood in the doorway watching the embrace, she saw a grim future: A child without her mother. This realization hit too close to home, she said. “I still think about that case.”
In her training, Dr. Rizack, now medical director of hematology/oncology at St. Anne’s in Fall River, Massachusetts, worked with a social worker who taught her how to deal with these tough cases — most importantly, how to not take them home with her.
Over the years, Dr. Rizack learned how to build and sustain a firm barrier between work and outside work.
She doesn’t go to funerals or give out her cell phone number. If charts need to be done, she prefers to stay late at the clinic instead of bringing them home.
And she invests in the simple moments that help her detach from the day-to-day in the clinic — rooting for her kids at their games, carving out time for family meals most days, and having relaxed movie nights on the couch.
“It’s hard sometimes,” she said. But “I really do need the line.” Because without it, she can’t show up for her patients the way she wants and needs to.
Establishing the work-life boundary means that when at work, Dr. Rizack can be all in for her patients. Even after her patients’ treatment ends, she makes sure to check on them at home or in hospice. For her, sticking with patients over the long term offers some closure.
“I want to love work, and if I’m there all the time, I’m not going to love it,” she said.
Trading Funerals for the Bedside
Like many other oncologists, Charles Blanke, MD, finds that going to patients’ funerals makes the loss seem more profound. Being at the bedside when they die is not as painful, he said. In fact, being there when his patients die offers him some comfort. He rarely misses a patient’s death because now Dr. Blanke’s patients can schedule their departure.
An oncologist at the Knight Cancer Institute in Portland, Oregon, Dr. Blanke specializes in end-of-life care with an emphasis on death with dignity, also known as medical aid in dying. He admits it’s not a role every physician is comfortable with.
“If you’re paralyzed by grief, you can’t do this for a living,” he said. But he’s able to do the work because he genuinely feels he’s helping patients get “the relief they so strongly desire” in their last moments.
When cancer care can’t give them the life they wanted, he can give them control over when and how they die. And the ability to honor their last wishes offers him some closure as well.
“You know what kind of end they have. You know it was peaceful. You see them achieve the thing that was the most important to them,” he said.
Despite this process, he still encounters some circumstances utterly heart-wrenching — the very young patients who have advanced disease. Some of these patients choose to die because they can’t afford to continue treatment. Others don’t have a support system. In these instances, Dr. Blanke is often the only one in the room.
Believe it or not, he said, the paperwork — and there’s a lot of it in his line of work — helps remind Dr. Blanke that patients’ last wishes are being honored.
Making Changes
After Dr. Lewis was confronted by his partner, he began to face the shortcomings of his own coping strategies. His practice hired a social worker to help staff process difficult experiences. After the loss of every patient, the practice comes together to share and process the loss.
For him, funerals remain helpful, providing a sort of solace, so he continues to go when he can. But how to grieve is something each doctor has to figure out, he said.
Deaths still hit hard, especially the ones he doesn’t see coming. The patients who remind him of his dad can also be hard. They restart a cycle of grief from his teenage years.
The difference now is he has space to voice those concerns and someone objective to help his process.
“It’s a privilege to prepare [patients for death] and help them build their legacy,” he said. But it’s also an unrelenting challenge to navigate that grief, he said.
Still, the grief lets Dr. Lewis know he’s still engaged.
“The day I don’t feel something is probably the day I need to take a break or walk away.”
A version of this article appeared on Medscape.com.
Dr. Lewis was well acquainted with cancer grief long before he became an oncologist. Dr. Lewis’ father died of a rare, hereditary cancer syndrome when he was only 14. The condition, which causes tumors to grow in the endocrine glands, can be hard to identify and, if found late, deadly.
In some ways, Dr. Lewis’ career caring for patients with advanced cancers was born out of that first loss. He centered his practice around helping patients diagnosed at late stages, like his father.
But that comes at a cost. Many patients will die.
Dr. Lewis’ encounter with his colleague led him to inventory his practice. He found that well over half of his patients died within 2 years following their advanced cancer diagnosis.
To stave off the grief of so many losses, Dr. Lewis became an eternal optimist in the clinic, in search of the Hail Mary chemotherapy, any way to eke out a few more months only to be ambushed by grief when a patient did finally pass.
At funerals — which he made every effort to attend — Dr. Lewis couldn’t help but think, “If I had done my job better, none of us with be here.” His grief started to mingle with this sense of guilt.
It became a cycle: Denial shrouded in optimism, grief, then a toxic guilt. The pattern became untenable for his colleagues. And his partner finally called him out.
Few medical specialties draw physicians as close to their patients as oncology. The long courses of treatment-spanning years can foster an intimacy that is comforting for patients and fulfilling for physicians. But that closeness can also set doctors up for an acute grief when the end of life comes.
Experts agree that no amount of training in medical school prepares an oncologist to navigate the grief that comes with losing patients. Five oncologists spoke with this news organization about the boundaries they rely on to sustain their careers.
Don’t Go to Funerals
Don Dizon, MD, who specializes in women’s cancers, established an essential boundary 20 years ago: Never go to funerals. In his early days at Memorial Sloan Kettering Cancer Center, the death of each patient dealt him a crushing blow. He’d go to the funerals in search of closure, but that only added to the weight of his grief.
“When I started in oncology, I just remember the most tragic cases were the ones I was taking care of,” recalled Dr. Dizon, now director of the Pelvic Malignancies Program at Lifespan Cancer Institute in Lincoln, Rhode Island.
Dr. Dizon recalled one young mother who was diagnosed with ovarian cancer. She responded to treatment, but it was short-lived, and her cancer progressed, he said. Multiple treatments followed, but none were effective. Eventually, Dr. Dizon had to tell her that “there’s nothing left to try.”
At her funeral, watching her grieving husband with their daughter who had just started to walk, Dr. Dizon was overwhelmed with despair.
“When you have to do this multiple times a year,” the grief becomes untenable, he said. Sensing the difficulty I was having as a new attending, “my boss stopped sending me patients because he knew I was in trouble emotionally.”
That’s when Dr. Dizon started looking for other ways to get closure.
Today, he tries to say his goodbyes before a patient dies. After the final treatment or before hospice, Dr. Dizon has a parting conversation with his patients to express the privilege of caring for them and all he learned from them. These talks help him and his patient connect in their last moments together.
The Price of Wildly Happy Days
Molly Taylor, MD, MS, a pediatric oncologist in Seattle, sees the deeply sad days as the price an oncologist pays to be witness to the “wildly happy ones.”
Dr. Taylor has gone to patients’ funerals, has even been asked to speak at them, but she has also attended patients’ weddings.
To some degree, doctors get good at compartmentalizing, and they become accustomed to tragedy, she said. But there are some patients who stick with you, “and that is a whole other level of grief,” Dr. Taylor said.
Several years into her practice, one of Dr. Taylor’s patients, someone who reminded her of her own child, died. The death came as a surprise, and the finality of it took her breath away, she said. The sadness only deepened as days went by. “I felt that mother’s grief and still do,” she said.
The patient’s funeral was one of the most difficult moments in her career as an oncologist. Even weeks later, she caught herself picturing the family huddled together that day.
Taking long walks, commiserating with colleagues who get it, and watching the occasional cat video can help take the immediate sting away. But the pain of losing a patient can be long lasting and processing that grief can be a lonely endeavor.
“We need space to recognize grief for all providers, all the people that touch these patients’ lives — the nurses, the translators, the cleaning staff,” Dr. Taylor said. Otherwise, you start to believe you’re the only one feeling the weight of the loss.
While it doesn’t make the losses any less poignant, Dr. Taylor finds solace in the good moments: Patient graduations and weddings, survivors who now volunteer at the hospital, and a patient who had a baby of her own this past year. If facing grief daily has taught Dr. Taylor anything, it is to not let the good moments pass unnoticed.
Towing the Line
Ten years ago, Tina Rizack, MD, walked into the ICU to see a young mother holding her 6-year-old daughter. The mother had necrotizing fasciitis that had gone undiagnosed.
As Dr. Rizack stood in the doorway watching the embrace, she saw a grim future: A child without her mother. This realization hit too close to home, she said. “I still think about that case.”
In her training, Dr. Rizack, now medical director of hematology/oncology at St. Anne’s in Fall River, Massachusetts, worked with a social worker who taught her how to deal with these tough cases — most importantly, how to not take them home with her.
Over the years, Dr. Rizack learned how to build and sustain a firm barrier between work and outside work.
She doesn’t go to funerals or give out her cell phone number. If charts need to be done, she prefers to stay late at the clinic instead of bringing them home.
And she invests in the simple moments that help her detach from the day-to-day in the clinic — rooting for her kids at their games, carving out time for family meals most days, and having relaxed movie nights on the couch.
“It’s hard sometimes,” she said. But “I really do need the line.” Because without it, she can’t show up for her patients the way she wants and needs to.
Establishing the work-life boundary means that when at work, Dr. Rizack can be all in for her patients. Even after her patients’ treatment ends, she makes sure to check on them at home or in hospice. For her, sticking with patients over the long term offers some closure.
“I want to love work, and if I’m there all the time, I’m not going to love it,” she said.
Trading Funerals for the Bedside
Like many other oncologists, Charles Blanke, MD, finds that going to patients’ funerals makes the loss seem more profound. Being at the bedside when they die is not as painful, he said. In fact, being there when his patients die offers him some comfort. He rarely misses a patient’s death because now Dr. Blanke’s patients can schedule their departure.
An oncologist at the Knight Cancer Institute in Portland, Oregon, Dr. Blanke specializes in end-of-life care with an emphasis on death with dignity, also known as medical aid in dying. He admits it’s not a role every physician is comfortable with.
“If you’re paralyzed by grief, you can’t do this for a living,” he said. But he’s able to do the work because he genuinely feels he’s helping patients get “the relief they so strongly desire” in their last moments.
When cancer care can’t give them the life they wanted, he can give them control over when and how they die. And the ability to honor their last wishes offers him some closure as well.
“You know what kind of end they have. You know it was peaceful. You see them achieve the thing that was the most important to them,” he said.
Despite this process, he still encounters some circumstances utterly heart-wrenching — the very young patients who have advanced disease. Some of these patients choose to die because they can’t afford to continue treatment. Others don’t have a support system. In these instances, Dr. Blanke is often the only one in the room.
Believe it or not, he said, the paperwork — and there’s a lot of it in his line of work — helps remind Dr. Blanke that patients’ last wishes are being honored.
Making Changes
After Dr. Lewis was confronted by his partner, he began to face the shortcomings of his own coping strategies. His practice hired a social worker to help staff process difficult experiences. After the loss of every patient, the practice comes together to share and process the loss.
For him, funerals remain helpful, providing a sort of solace, so he continues to go when he can. But how to grieve is something each doctor has to figure out, he said.
Deaths still hit hard, especially the ones he doesn’t see coming. The patients who remind him of his dad can also be hard. They restart a cycle of grief from his teenage years.
The difference now is he has space to voice those concerns and someone objective to help his process.
“It’s a privilege to prepare [patients for death] and help them build their legacy,” he said. But it’s also an unrelenting challenge to navigate that grief, he said.
Still, the grief lets Dr. Lewis know he’s still engaged.
“The day I don’t feel something is probably the day I need to take a break or walk away.”
A version of this article appeared on Medscape.com.
Dr. Lewis was well acquainted with cancer grief long before he became an oncologist. Dr. Lewis’ father died of a rare, hereditary cancer syndrome when he was only 14. The condition, which causes tumors to grow in the endocrine glands, can be hard to identify and, if found late, deadly.
In some ways, Dr. Lewis’ career caring for patients with advanced cancers was born out of that first loss. He centered his practice around helping patients diagnosed at late stages, like his father.
But that comes at a cost. Many patients will die.
Dr. Lewis’ encounter with his colleague led him to inventory his practice. He found that well over half of his patients died within 2 years following their advanced cancer diagnosis.
To stave off the grief of so many losses, Dr. Lewis became an eternal optimist in the clinic, in search of the Hail Mary chemotherapy, any way to eke out a few more months only to be ambushed by grief when a patient did finally pass.
At funerals — which he made every effort to attend — Dr. Lewis couldn’t help but think, “If I had done my job better, none of us with be here.” His grief started to mingle with this sense of guilt.
It became a cycle: Denial shrouded in optimism, grief, then a toxic guilt. The pattern became untenable for his colleagues. And his partner finally called him out.
Few medical specialties draw physicians as close to their patients as oncology. The long courses of treatment-spanning years can foster an intimacy that is comforting for patients and fulfilling for physicians. But that closeness can also set doctors up for an acute grief when the end of life comes.
Experts agree that no amount of training in medical school prepares an oncologist to navigate the grief that comes with losing patients. Five oncologists spoke with this news organization about the boundaries they rely on to sustain their careers.
Don’t Go to Funerals
Don Dizon, MD, who specializes in women’s cancers, established an essential boundary 20 years ago: Never go to funerals. In his early days at Memorial Sloan Kettering Cancer Center, the death of each patient dealt him a crushing blow. He’d go to the funerals in search of closure, but that only added to the weight of his grief.
“When I started in oncology, I just remember the most tragic cases were the ones I was taking care of,” recalled Dr. Dizon, now director of the Pelvic Malignancies Program at Lifespan Cancer Institute in Lincoln, Rhode Island.
Dr. Dizon recalled one young mother who was diagnosed with ovarian cancer. She responded to treatment, but it was short-lived, and her cancer progressed, he said. Multiple treatments followed, but none were effective. Eventually, Dr. Dizon had to tell her that “there’s nothing left to try.”
At her funeral, watching her grieving husband with their daughter who had just started to walk, Dr. Dizon was overwhelmed with despair.
“When you have to do this multiple times a year,” the grief becomes untenable, he said. Sensing the difficulty I was having as a new attending, “my boss stopped sending me patients because he knew I was in trouble emotionally.”
That’s when Dr. Dizon started looking for other ways to get closure.
Today, he tries to say his goodbyes before a patient dies. After the final treatment or before hospice, Dr. Dizon has a parting conversation with his patients to express the privilege of caring for them and all he learned from them. These talks help him and his patient connect in their last moments together.
The Price of Wildly Happy Days
Molly Taylor, MD, MS, a pediatric oncologist in Seattle, sees the deeply sad days as the price an oncologist pays to be witness to the “wildly happy ones.”
Dr. Taylor has gone to patients’ funerals, has even been asked to speak at them, but she has also attended patients’ weddings.
To some degree, doctors get good at compartmentalizing, and they become accustomed to tragedy, she said. But there are some patients who stick with you, “and that is a whole other level of grief,” Dr. Taylor said.
Several years into her practice, one of Dr. Taylor’s patients, someone who reminded her of her own child, died. The death came as a surprise, and the finality of it took her breath away, she said. The sadness only deepened as days went by. “I felt that mother’s grief and still do,” she said.
The patient’s funeral was one of the most difficult moments in her career as an oncologist. Even weeks later, she caught herself picturing the family huddled together that day.
Taking long walks, commiserating with colleagues who get it, and watching the occasional cat video can help take the immediate sting away. But the pain of losing a patient can be long lasting and processing that grief can be a lonely endeavor.
“We need space to recognize grief for all providers, all the people that touch these patients’ lives — the nurses, the translators, the cleaning staff,” Dr. Taylor said. Otherwise, you start to believe you’re the only one feeling the weight of the loss.
While it doesn’t make the losses any less poignant, Dr. Taylor finds solace in the good moments: Patient graduations and weddings, survivors who now volunteer at the hospital, and a patient who had a baby of her own this past year. If facing grief daily has taught Dr. Taylor anything, it is to not let the good moments pass unnoticed.
Towing the Line
Ten years ago, Tina Rizack, MD, walked into the ICU to see a young mother holding her 6-year-old daughter. The mother had necrotizing fasciitis that had gone undiagnosed.
As Dr. Rizack stood in the doorway watching the embrace, she saw a grim future: A child without her mother. This realization hit too close to home, she said. “I still think about that case.”
In her training, Dr. Rizack, now medical director of hematology/oncology at St. Anne’s in Fall River, Massachusetts, worked with a social worker who taught her how to deal with these tough cases — most importantly, how to not take them home with her.
Over the years, Dr. Rizack learned how to build and sustain a firm barrier between work and outside work.
She doesn’t go to funerals or give out her cell phone number. If charts need to be done, she prefers to stay late at the clinic instead of bringing them home.
And she invests in the simple moments that help her detach from the day-to-day in the clinic — rooting for her kids at their games, carving out time for family meals most days, and having relaxed movie nights on the couch.
“It’s hard sometimes,” she said. But “I really do need the line.” Because without it, she can’t show up for her patients the way she wants and needs to.
Establishing the work-life boundary means that when at work, Dr. Rizack can be all in for her patients. Even after her patients’ treatment ends, she makes sure to check on them at home or in hospice. For her, sticking with patients over the long term offers some closure.
“I want to love work, and if I’m there all the time, I’m not going to love it,” she said.
Trading Funerals for the Bedside
Like many other oncologists, Charles Blanke, MD, finds that going to patients’ funerals makes the loss seem more profound. Being at the bedside when they die is not as painful, he said. In fact, being there when his patients die offers him some comfort. He rarely misses a patient’s death because now Dr. Blanke’s patients can schedule their departure.
An oncologist at the Knight Cancer Institute in Portland, Oregon, Dr. Blanke specializes in end-of-life care with an emphasis on death with dignity, also known as medical aid in dying. He admits it’s not a role every physician is comfortable with.
“If you’re paralyzed by grief, you can’t do this for a living,” he said. But he’s able to do the work because he genuinely feels he’s helping patients get “the relief they so strongly desire” in their last moments.
When cancer care can’t give them the life they wanted, he can give them control over when and how they die. And the ability to honor their last wishes offers him some closure as well.
“You know what kind of end they have. You know it was peaceful. You see them achieve the thing that was the most important to them,” he said.
Despite this process, he still encounters some circumstances utterly heart-wrenching — the very young patients who have advanced disease. Some of these patients choose to die because they can’t afford to continue treatment. Others don’t have a support system. In these instances, Dr. Blanke is often the only one in the room.
Believe it or not, he said, the paperwork — and there’s a lot of it in his line of work — helps remind Dr. Blanke that patients’ last wishes are being honored.
Making Changes
After Dr. Lewis was confronted by his partner, he began to face the shortcomings of his own coping strategies. His practice hired a social worker to help staff process difficult experiences. After the loss of every patient, the practice comes together to share and process the loss.
For him, funerals remain helpful, providing a sort of solace, so he continues to go when he can. But how to grieve is something each doctor has to figure out, he said.
Deaths still hit hard, especially the ones he doesn’t see coming. The patients who remind him of his dad can also be hard. They restart a cycle of grief from his teenage years.
The difference now is he has space to voice those concerns and someone objective to help his process.
“It’s a privilege to prepare [patients for death] and help them build their legacy,” he said. But it’s also an unrelenting challenge to navigate that grief, he said.
Still, the grief lets Dr. Lewis know he’s still engaged.
“The day I don’t feel something is probably the day I need to take a break or walk away.”
A version of this article appeared on Medscape.com.
FDA Withdraws Melflufen Approval, but EMA Still Allows Its Use
But the European Medicines Agency (EMA) still authorizes the drug’s manufacturer Oncopeptides AB to market the drug, also called Pepaxti, in Europe, Iceland, Lichtenstein, Norway, and the United Kingdom.
Amol Akhade, MBBS, who describes himself as a senior consultant medical and hemato oncologist–bone marrow transplant physician on LinkedIn, raised questions about the inconsistencies between the FDA and EMA’s opinions about these drugs. Dr. Akhad, of Suyog Cancer Clinics in India, posted via the following handle @SuyogCancer on X (Twitter):
“How can one drug and one trial data [have] two diagonally different outcomes from two different drug approval agencies?
Melphalan Flufenamide is finally completely withdrawn by @US_FDA
But approval by @EMA_News stays.
How can be one drug be harmful across one side of Atlantic Ocean and becomes safe and useful on the other side of Atlantic Ocean?
Modern day miracle?”
EMA: Pepaxti’s Benefits Exceed Its Risks
The EMA, which could not be reached for comment regarding why the agency was still allowing patients to use the drug, said the following about Pepaxti on its website:
“The European Medicines Agency decided that Pepaxti’s benefits are greater than its risks and it can be authorised for use in the EU. The Agency noted the unmet medical need for patients with multiple myeloma who no longer improve with the available therapies. Despite some limitations in the studies, the results were considered clinically relevant, with the exception of the subgroup of patients who had an autologous stem cell transplant and whose disease progressed within three years of transplantation.
Regarding safety, although side effects, including severe effects, were seen with treatment involving Pepaxti, these were considered acceptable and manageable,” the agency wrote.
“Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pepaxti have been included in the summary of product characteristics and the package leaflet.
As for all medicines, data on the use of Pepaxti are continuously monitored. Suspected side effects reported with Pepaxti are carefully evaluated and any necessary action taken to protect patients,” according to the EMA.
The FDA’s final decision, issued on February 23, 2024, follows its warning in 2021 that meflufen plus dexamethasone exposed patients with multiple myeloma to increased risk for death, and its call for withdrawal of the drug in 2022.
“The grounds for withdrawing approval have been met because: (1) the confirmatory study conducted as a condition of accelerated approval did not confirm Pepaxto’s clinical benefit and (2) the available evidence demonstrates that Pepaxto is not shown to be safe or effective under its conditions of use,” Peter Marks, MD, PhD, Director of the FDA Center for Biologics Evaluation and Research, wrote in the final decision document.
Oncopeptides AB: Drug ‘Caters to a Large Unmet Need’
David Augustsson, Director of Corporate Affairs, Oncopeptides AB, explained in an interview why he thinks the EMA and FDA’s actions regarding the drug differ from each other.
“The European Medicines Agency had the opinion that the OCEAN study met its primary endpoint by demonstrating superior progression-free survival and it agreed that the potential detriment of overall survival was limited to patients progressing less than 36 months after an autologous stem cell transplant,” he said.“The FDA was not willing to acknowledge the observed clinically relevant differences across patient subgroups in the OCEAN study as confirmed.”
Mr. Augustsson added that this decision will deprive US patients of access to “a drug we believe caters to a large unmet need among elderly multiple myeloma patients with few treatment options left.”
“While we remain confident that we have science on our side we are of course disappointed in the decision [to remove Pepaxto from the US market],” Oncopeptides AB CEO Sofia Heigis said in a statement. “At the same time this is no change to our plans and we will continue to focus all our attention on the commercialization in Europe, progression of our pipeline and rest of world opportunities.”
FDA 'Took Swift Action' to Ensure Users of Pepaxto Were Informed of Risks
In February 2021, the FDA used the Accelerated Approval Program to enable certain patients with multiple myeloma to be treated with the peptide conjugated alkylating drug melflufen plus dexamethasone. Under the program, Oncopeptides was required to conduct the phase III randomized, controlled OCEAN clinical trial.
OCEAN enrolled 495 patients with relapsed/refractory multiple myeloma who had 2 to 4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy. Participants in the multinational study received either melflufen plus dexamethasone or pomalidomide plus dexamethasone until disease progression, unacceptable toxicity, or lack of benefit.
In July 2021, the FDA issued an alert that the study results showed increased risk for death in participants treated with melflufen. In October that year, at FDA request, Oncopeptides removed the drug from the US market but continued to provide it to patients already receiving it. In December 2022, the FDA requested that the company withdraw melflufen’s US marketing authorization.
Responding to questions about the timing of the FDA’s most recent decision about Pepaxto and how the decision will affect patient care in the US, the FDA emailed the following statement to this news organization:
“Since the OCEAN trial results for Pepaxto in 2021, the FDA has responded to safety concerns about Pepaxto by issuing a CDER Alert, communicating concerns to Oncopeptides, holding an Oncologic Drugs Advisory Committee meeting in September 2022, and issuing a letter of notice to Oncopeptides in July 2023, proposing to withdraw Pepaxto (NDA 214383). After receiving the notice, Oncopeptides appealed the withdrawal in August 2023. A meeting was held with the Commissioner’s designee, Dr. Peter Marks, Oncopeptides, and others from FDA in October 2023. Dr. Marks reviewed the record and considered the arguments made on appeal and issued a final decision on February 23, 2024. Prior to reaching a decision, the FDA took swift action to ensure those receiving Pepaxto in the post-confirmatory clinical trial were informed of the risks and that no new patients were enrolled in the trial. We also note that it is our understanding that Pepaxto has not been marketed in the U.S. since October 22, 2021.”
“This is the first time FDA has used the amended procedures for withdrawal of accelerated approval that were enacted in 2023, as part of the Food and Drug Omnibus Report Act of 2022 (FDORA),” the agency wrote in a Feb 23 statement. The agency will also remove melflufen from the Approved Drug Products with Therapeutic Equivalence Evaluations, also called the Orange Book.
But the European Medicines Agency (EMA) still authorizes the drug’s manufacturer Oncopeptides AB to market the drug, also called Pepaxti, in Europe, Iceland, Lichtenstein, Norway, and the United Kingdom.
Amol Akhade, MBBS, who describes himself as a senior consultant medical and hemato oncologist–bone marrow transplant physician on LinkedIn, raised questions about the inconsistencies between the FDA and EMA’s opinions about these drugs. Dr. Akhad, of Suyog Cancer Clinics in India, posted via the following handle @SuyogCancer on X (Twitter):
“How can one drug and one trial data [have] two diagonally different outcomes from two different drug approval agencies?
Melphalan Flufenamide is finally completely withdrawn by @US_FDA
But approval by @EMA_News stays.
How can be one drug be harmful across one side of Atlantic Ocean and becomes safe and useful on the other side of Atlantic Ocean?
Modern day miracle?”
EMA: Pepaxti’s Benefits Exceed Its Risks
The EMA, which could not be reached for comment regarding why the agency was still allowing patients to use the drug, said the following about Pepaxti on its website:
“The European Medicines Agency decided that Pepaxti’s benefits are greater than its risks and it can be authorised for use in the EU. The Agency noted the unmet medical need for patients with multiple myeloma who no longer improve with the available therapies. Despite some limitations in the studies, the results were considered clinically relevant, with the exception of the subgroup of patients who had an autologous stem cell transplant and whose disease progressed within three years of transplantation.
Regarding safety, although side effects, including severe effects, were seen with treatment involving Pepaxti, these were considered acceptable and manageable,” the agency wrote.
“Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pepaxti have been included in the summary of product characteristics and the package leaflet.
As for all medicines, data on the use of Pepaxti are continuously monitored. Suspected side effects reported with Pepaxti are carefully evaluated and any necessary action taken to protect patients,” according to the EMA.
The FDA’s final decision, issued on February 23, 2024, follows its warning in 2021 that meflufen plus dexamethasone exposed patients with multiple myeloma to increased risk for death, and its call for withdrawal of the drug in 2022.
“The grounds for withdrawing approval have been met because: (1) the confirmatory study conducted as a condition of accelerated approval did not confirm Pepaxto’s clinical benefit and (2) the available evidence demonstrates that Pepaxto is not shown to be safe or effective under its conditions of use,” Peter Marks, MD, PhD, Director of the FDA Center for Biologics Evaluation and Research, wrote in the final decision document.
Oncopeptides AB: Drug ‘Caters to a Large Unmet Need’
David Augustsson, Director of Corporate Affairs, Oncopeptides AB, explained in an interview why he thinks the EMA and FDA’s actions regarding the drug differ from each other.
“The European Medicines Agency had the opinion that the OCEAN study met its primary endpoint by demonstrating superior progression-free survival and it agreed that the potential detriment of overall survival was limited to patients progressing less than 36 months after an autologous stem cell transplant,” he said.“The FDA was not willing to acknowledge the observed clinically relevant differences across patient subgroups in the OCEAN study as confirmed.”
Mr. Augustsson added that this decision will deprive US patients of access to “a drug we believe caters to a large unmet need among elderly multiple myeloma patients with few treatment options left.”
“While we remain confident that we have science on our side we are of course disappointed in the decision [to remove Pepaxto from the US market],” Oncopeptides AB CEO Sofia Heigis said in a statement. “At the same time this is no change to our plans and we will continue to focus all our attention on the commercialization in Europe, progression of our pipeline and rest of world opportunities.”
FDA 'Took Swift Action' to Ensure Users of Pepaxto Were Informed of Risks
In February 2021, the FDA used the Accelerated Approval Program to enable certain patients with multiple myeloma to be treated with the peptide conjugated alkylating drug melflufen plus dexamethasone. Under the program, Oncopeptides was required to conduct the phase III randomized, controlled OCEAN clinical trial.
OCEAN enrolled 495 patients with relapsed/refractory multiple myeloma who had 2 to 4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy. Participants in the multinational study received either melflufen plus dexamethasone or pomalidomide plus dexamethasone until disease progression, unacceptable toxicity, or lack of benefit.
In July 2021, the FDA issued an alert that the study results showed increased risk for death in participants treated with melflufen. In October that year, at FDA request, Oncopeptides removed the drug from the US market but continued to provide it to patients already receiving it. In December 2022, the FDA requested that the company withdraw melflufen’s US marketing authorization.
Responding to questions about the timing of the FDA’s most recent decision about Pepaxto and how the decision will affect patient care in the US, the FDA emailed the following statement to this news organization:
“Since the OCEAN trial results for Pepaxto in 2021, the FDA has responded to safety concerns about Pepaxto by issuing a CDER Alert, communicating concerns to Oncopeptides, holding an Oncologic Drugs Advisory Committee meeting in September 2022, and issuing a letter of notice to Oncopeptides in July 2023, proposing to withdraw Pepaxto (NDA 214383). After receiving the notice, Oncopeptides appealed the withdrawal in August 2023. A meeting was held with the Commissioner’s designee, Dr. Peter Marks, Oncopeptides, and others from FDA in October 2023. Dr. Marks reviewed the record and considered the arguments made on appeal and issued a final decision on February 23, 2024. Prior to reaching a decision, the FDA took swift action to ensure those receiving Pepaxto in the post-confirmatory clinical trial were informed of the risks and that no new patients were enrolled in the trial. We also note that it is our understanding that Pepaxto has not been marketed in the U.S. since October 22, 2021.”
“This is the first time FDA has used the amended procedures for withdrawal of accelerated approval that were enacted in 2023, as part of the Food and Drug Omnibus Report Act of 2022 (FDORA),” the agency wrote in a Feb 23 statement. The agency will also remove melflufen from the Approved Drug Products with Therapeutic Equivalence Evaluations, also called the Orange Book.
But the European Medicines Agency (EMA) still authorizes the drug’s manufacturer Oncopeptides AB to market the drug, also called Pepaxti, in Europe, Iceland, Lichtenstein, Norway, and the United Kingdom.
Amol Akhade, MBBS, who describes himself as a senior consultant medical and hemato oncologist–bone marrow transplant physician on LinkedIn, raised questions about the inconsistencies between the FDA and EMA’s opinions about these drugs. Dr. Akhad, of Suyog Cancer Clinics in India, posted via the following handle @SuyogCancer on X (Twitter):
“How can one drug and one trial data [have] two diagonally different outcomes from two different drug approval agencies?
Melphalan Flufenamide is finally completely withdrawn by @US_FDA
But approval by @EMA_News stays.
How can be one drug be harmful across one side of Atlantic Ocean and becomes safe and useful on the other side of Atlantic Ocean?
Modern day miracle?”
EMA: Pepaxti’s Benefits Exceed Its Risks
The EMA, which could not be reached for comment regarding why the agency was still allowing patients to use the drug, said the following about Pepaxti on its website:
“The European Medicines Agency decided that Pepaxti’s benefits are greater than its risks and it can be authorised for use in the EU. The Agency noted the unmet medical need for patients with multiple myeloma who no longer improve with the available therapies. Despite some limitations in the studies, the results were considered clinically relevant, with the exception of the subgroup of patients who had an autologous stem cell transplant and whose disease progressed within three years of transplantation.
Regarding safety, although side effects, including severe effects, were seen with treatment involving Pepaxti, these were considered acceptable and manageable,” the agency wrote.
“Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pepaxti have been included in the summary of product characteristics and the package leaflet.
As for all medicines, data on the use of Pepaxti are continuously monitored. Suspected side effects reported with Pepaxti are carefully evaluated and any necessary action taken to protect patients,” according to the EMA.
The FDA’s final decision, issued on February 23, 2024, follows its warning in 2021 that meflufen plus dexamethasone exposed patients with multiple myeloma to increased risk for death, and its call for withdrawal of the drug in 2022.
“The grounds for withdrawing approval have been met because: (1) the confirmatory study conducted as a condition of accelerated approval did not confirm Pepaxto’s clinical benefit and (2) the available evidence demonstrates that Pepaxto is not shown to be safe or effective under its conditions of use,” Peter Marks, MD, PhD, Director of the FDA Center for Biologics Evaluation and Research, wrote in the final decision document.
Oncopeptides AB: Drug ‘Caters to a Large Unmet Need’
David Augustsson, Director of Corporate Affairs, Oncopeptides AB, explained in an interview why he thinks the EMA and FDA’s actions regarding the drug differ from each other.
“The European Medicines Agency had the opinion that the OCEAN study met its primary endpoint by demonstrating superior progression-free survival and it agreed that the potential detriment of overall survival was limited to patients progressing less than 36 months after an autologous stem cell transplant,” he said.“The FDA was not willing to acknowledge the observed clinically relevant differences across patient subgroups in the OCEAN study as confirmed.”
Mr. Augustsson added that this decision will deprive US patients of access to “a drug we believe caters to a large unmet need among elderly multiple myeloma patients with few treatment options left.”
“While we remain confident that we have science on our side we are of course disappointed in the decision [to remove Pepaxto from the US market],” Oncopeptides AB CEO Sofia Heigis said in a statement. “At the same time this is no change to our plans and we will continue to focus all our attention on the commercialization in Europe, progression of our pipeline and rest of world opportunities.”
FDA 'Took Swift Action' to Ensure Users of Pepaxto Were Informed of Risks
In February 2021, the FDA used the Accelerated Approval Program to enable certain patients with multiple myeloma to be treated with the peptide conjugated alkylating drug melflufen plus dexamethasone. Under the program, Oncopeptides was required to conduct the phase III randomized, controlled OCEAN clinical trial.
OCEAN enrolled 495 patients with relapsed/refractory multiple myeloma who had 2 to 4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy. Participants in the multinational study received either melflufen plus dexamethasone or pomalidomide plus dexamethasone until disease progression, unacceptable toxicity, or lack of benefit.
In July 2021, the FDA issued an alert that the study results showed increased risk for death in participants treated with melflufen. In October that year, at FDA request, Oncopeptides removed the drug from the US market but continued to provide it to patients already receiving it. In December 2022, the FDA requested that the company withdraw melflufen’s US marketing authorization.
Responding to questions about the timing of the FDA’s most recent decision about Pepaxto and how the decision will affect patient care in the US, the FDA emailed the following statement to this news organization:
“Since the OCEAN trial results for Pepaxto in 2021, the FDA has responded to safety concerns about Pepaxto by issuing a CDER Alert, communicating concerns to Oncopeptides, holding an Oncologic Drugs Advisory Committee meeting in September 2022, and issuing a letter of notice to Oncopeptides in July 2023, proposing to withdraw Pepaxto (NDA 214383). After receiving the notice, Oncopeptides appealed the withdrawal in August 2023. A meeting was held with the Commissioner’s designee, Dr. Peter Marks, Oncopeptides, and others from FDA in October 2023. Dr. Marks reviewed the record and considered the arguments made on appeal and issued a final decision on February 23, 2024. Prior to reaching a decision, the FDA took swift action to ensure those receiving Pepaxto in the post-confirmatory clinical trial were informed of the risks and that no new patients were enrolled in the trial. We also note that it is our understanding that Pepaxto has not been marketed in the U.S. since October 22, 2021.”
“This is the first time FDA has used the amended procedures for withdrawal of accelerated approval that were enacted in 2023, as part of the Food and Drug Omnibus Report Act of 2022 (FDORA),” the agency wrote in a Feb 23 statement. The agency will also remove melflufen from the Approved Drug Products with Therapeutic Equivalence Evaluations, also called the Orange Book.
What Happens to Surgery Candidates with BHDs and Cancer?
based on data from a new study of nearly 700,000 individuals.
The reason for this association remains unclear, and highlights the need to address existing behavioral health disorders (BHDs), which can be exacerbated after a patient is diagnosed with cancer, wrote Timothy M. Pawlik, MD, of The Ohio State University, Columbus, and colleagues. A cancer diagnosis can cause not only physical stress, but mental, emotional, social, and economic stress that can prompt a new BHD, cause relapse of a previous BHD, or exacerbate a current BHD, the researchers noted.
What is Known About BHDs and Cancer?
Although previous studies have shown a possible association between BHDs and increased cancer risk, as well as reduced compliance with care, the effect of BHDs on outcomes in cancer patients undergoing surgical resection has not been examined, wrote Dr. Pawlik and colleagues.
Previous research has focused on the impact of having a preexisting serious mental illness (SMI) such as schizophrenia and bipolar disorder on cancer care.
A 2023 literature review of 27 studies published in the Journal of Medical Imaging and Radiation Sciences showed that patients with preexisting severe mental illness (such as schizophrenia or bipolar disorder) had greater cancer-related mortality. In that study, the researchers also found that patients with severe mental illness were more likely to have metastatic disease at diagnosis, but less likely to receive optimal treatments, than individuals without SMIs.
Many studies also have focused on patients developing mental health problems (including BHDs) after a cancer diagnosis, but the current study is the first known to examine outcomes in those with BHDs before cancer.
Why Was It Important to Conduct This Study?
“BHDs are a diverse set of mental illnesses that affect an individual’s psychosocial wellbeing, potentially resulting in maladaptive behaviors,” Dr. Pawlik said in an interview. BHDs, which include substance abuse, eating disorders, and sleep disorders, are less common than anxiety/depression, but have an estimated prevalence of 1.3%-3.1% among adults in the United States, he said.
What Does the New Study Add?
In the new review by Dr. Pawlik and colleagues, published in the Journal of the American College of Surgeons (Katayama ES. J Am Coll Surg. 2024 Feb 29. doi: 2024. 10.1097/XCS.0000000000000954), BHDs were defined as substance abuse, eating disorders, or sleep disorders, which had not been the focus of previous studies. The researchers reviewed data from 694,836 adult patients with lung, esophageal, gastric, liver, pancreatic, or colorectal cancer between 2018-2021 using the Medicare Standard Analytic files. A total of 46,719 patients (6.7%) had at least one BHD.
Overall, patients with a BHD were significantly less likely than those without a BHD to undergo surgical resection (20.3% vs. 23.4%). Patients with a BHD also had significantly worse long-term postoperative survival than those without BHDs (median 37.1 months vs. 46.6 months) and significantly higher in-hospital costs ($17,432 vs. 16,159, P less than .001 for all).
Among patients who underwent cancer surgery, the odds of any complication were significantly higher for those with a BHD compared to those with no BHD (odds ratio 1.32), as were the odds of a prolonged length of stay (OR 1.67) and 90-day readmission (OR 1.57).
Dr. Pawlik said he was surprised by several of the findings, including that 1 in 15 Medicare beneficiaries had a BHD diagnosis, “with male sex and minority racial status, as well as higher social vulnerability, being associated with a higher prevalence of BHD.”
Also, the independent association of having a BHD with 30%-50% higher odds of a complication, prolonged length of stay, and 90-day readmission was higher than Dr. Pawlik had anticipated.
Why Do Patients With BHDs Have Fewer Surgeries and Worse Outcomes?
The reasons for this association were likely multifactorial and may reflect the greater burden of medical comorbidity and chronic illness in many patients with BHDs because of maladaptive lifestyles or poor nutrition status, Dr. Pawlik said.
“Patients with BHDs also likely face barriers to accessing care, which was noted particularly among patients with BHDs who lived in socially vulnerable areas,” he said. BHD patients also were more likely to be treated at low-volume rather than high-volume hospitals, “which undoubtedly contributed in part to worse outcomes in this cohort of patients,” he added.
What Can Oncologists Do to Help?
The take-home message for clinicians is that BHDs are linked to worse surgical outcomes and higher health care costs in cancer patients, Dr. Pawlik said in an interview.
“Enhanced accessibility to behavioral healthcare, as well as comprehensive policy reform related to mental health services are needed to improve care of patients with BHDs,” he said. “For example, implementing psychiatry compensation programs may encourage practice in vulnerable areas,” he said.
Other strategies include a following a collaborative care model involving mental health professionals working in tandem with primary care and mid-level practitioners and increasing use and establishment of telehealth systems to improve patient access to BHD services, he said.
What Are the Limitations?
The study by Dr. Pawlik and colleagues was limited by several factors, including the lack of data on younger patients and the full range of BHDs, as well as underreporting of BHDs and the high copays for mental health care, the researchers noted. However, the results suggest that concomitant BHDs are associated with worse cancer outcomes and higher in-hospital costs, and illustrate the need to screen for and target these conditions in cancer patients, the researchers concluded.
What Are the Next Steps for Research?
The current study involved Medicare beneficiaries aged 65 years or older, and more research is needed to investigate the impact of BHDs among younger cancer patients in whom the prevalence may be higher and the impact of BHDs may be different, Dr. Pawlik said in an interview. In addition, the analysis of BHDs as a composite of substance abuse, eating disorders, and sleep disorders (because the numbers were too small to break out data for each disorder, separately) prevented investigation of potential differences and unique challenges faced by distinct subpopulations of BHD patients, he said.
“Future studies should examine the individual impact of substance abuse, eating disorders, and sleep disorders on access to surgery, as well as the potential different impact that each one of these different BHDs may have on postoperative outcomes,” Dr. Pawlik suggested.
The study was supported by The Ohio State University College of Medicine Roessler Summer Research Scholarship. The researchers had no financial conflicts to disclose.
based on data from a new study of nearly 700,000 individuals.
The reason for this association remains unclear, and highlights the need to address existing behavioral health disorders (BHDs), which can be exacerbated after a patient is diagnosed with cancer, wrote Timothy M. Pawlik, MD, of The Ohio State University, Columbus, and colleagues. A cancer diagnosis can cause not only physical stress, but mental, emotional, social, and economic stress that can prompt a new BHD, cause relapse of a previous BHD, or exacerbate a current BHD, the researchers noted.
What is Known About BHDs and Cancer?
Although previous studies have shown a possible association between BHDs and increased cancer risk, as well as reduced compliance with care, the effect of BHDs on outcomes in cancer patients undergoing surgical resection has not been examined, wrote Dr. Pawlik and colleagues.
Previous research has focused on the impact of having a preexisting serious mental illness (SMI) such as schizophrenia and bipolar disorder on cancer care.
A 2023 literature review of 27 studies published in the Journal of Medical Imaging and Radiation Sciences showed that patients with preexisting severe mental illness (such as schizophrenia or bipolar disorder) had greater cancer-related mortality. In that study, the researchers also found that patients with severe mental illness were more likely to have metastatic disease at diagnosis, but less likely to receive optimal treatments, than individuals without SMIs.
Many studies also have focused on patients developing mental health problems (including BHDs) after a cancer diagnosis, but the current study is the first known to examine outcomes in those with BHDs before cancer.
Why Was It Important to Conduct This Study?
“BHDs are a diverse set of mental illnesses that affect an individual’s psychosocial wellbeing, potentially resulting in maladaptive behaviors,” Dr. Pawlik said in an interview. BHDs, which include substance abuse, eating disorders, and sleep disorders, are less common than anxiety/depression, but have an estimated prevalence of 1.3%-3.1% among adults in the United States, he said.
What Does the New Study Add?
In the new review by Dr. Pawlik and colleagues, published in the Journal of the American College of Surgeons (Katayama ES. J Am Coll Surg. 2024 Feb 29. doi: 2024. 10.1097/XCS.0000000000000954), BHDs were defined as substance abuse, eating disorders, or sleep disorders, which had not been the focus of previous studies. The researchers reviewed data from 694,836 adult patients with lung, esophageal, gastric, liver, pancreatic, or colorectal cancer between 2018-2021 using the Medicare Standard Analytic files. A total of 46,719 patients (6.7%) had at least one BHD.
Overall, patients with a BHD were significantly less likely than those without a BHD to undergo surgical resection (20.3% vs. 23.4%). Patients with a BHD also had significantly worse long-term postoperative survival than those without BHDs (median 37.1 months vs. 46.6 months) and significantly higher in-hospital costs ($17,432 vs. 16,159, P less than .001 for all).
Among patients who underwent cancer surgery, the odds of any complication were significantly higher for those with a BHD compared to those with no BHD (odds ratio 1.32), as were the odds of a prolonged length of stay (OR 1.67) and 90-day readmission (OR 1.57).
Dr. Pawlik said he was surprised by several of the findings, including that 1 in 15 Medicare beneficiaries had a BHD diagnosis, “with male sex and minority racial status, as well as higher social vulnerability, being associated with a higher prevalence of BHD.”
Also, the independent association of having a BHD with 30%-50% higher odds of a complication, prolonged length of stay, and 90-day readmission was higher than Dr. Pawlik had anticipated.
Why Do Patients With BHDs Have Fewer Surgeries and Worse Outcomes?
The reasons for this association were likely multifactorial and may reflect the greater burden of medical comorbidity and chronic illness in many patients with BHDs because of maladaptive lifestyles or poor nutrition status, Dr. Pawlik said.
“Patients with BHDs also likely face barriers to accessing care, which was noted particularly among patients with BHDs who lived in socially vulnerable areas,” he said. BHD patients also were more likely to be treated at low-volume rather than high-volume hospitals, “which undoubtedly contributed in part to worse outcomes in this cohort of patients,” he added.
What Can Oncologists Do to Help?
The take-home message for clinicians is that BHDs are linked to worse surgical outcomes and higher health care costs in cancer patients, Dr. Pawlik said in an interview.
“Enhanced accessibility to behavioral healthcare, as well as comprehensive policy reform related to mental health services are needed to improve care of patients with BHDs,” he said. “For example, implementing psychiatry compensation programs may encourage practice in vulnerable areas,” he said.
Other strategies include a following a collaborative care model involving mental health professionals working in tandem with primary care and mid-level practitioners and increasing use and establishment of telehealth systems to improve patient access to BHD services, he said.
What Are the Limitations?
The study by Dr. Pawlik and colleagues was limited by several factors, including the lack of data on younger patients and the full range of BHDs, as well as underreporting of BHDs and the high copays for mental health care, the researchers noted. However, the results suggest that concomitant BHDs are associated with worse cancer outcomes and higher in-hospital costs, and illustrate the need to screen for and target these conditions in cancer patients, the researchers concluded.
What Are the Next Steps for Research?
The current study involved Medicare beneficiaries aged 65 years or older, and more research is needed to investigate the impact of BHDs among younger cancer patients in whom the prevalence may be higher and the impact of BHDs may be different, Dr. Pawlik said in an interview. In addition, the analysis of BHDs as a composite of substance abuse, eating disorders, and sleep disorders (because the numbers were too small to break out data for each disorder, separately) prevented investigation of potential differences and unique challenges faced by distinct subpopulations of BHD patients, he said.
“Future studies should examine the individual impact of substance abuse, eating disorders, and sleep disorders on access to surgery, as well as the potential different impact that each one of these different BHDs may have on postoperative outcomes,” Dr. Pawlik suggested.
The study was supported by The Ohio State University College of Medicine Roessler Summer Research Scholarship. The researchers had no financial conflicts to disclose.
based on data from a new study of nearly 700,000 individuals.
The reason for this association remains unclear, and highlights the need to address existing behavioral health disorders (BHDs), which can be exacerbated after a patient is diagnosed with cancer, wrote Timothy M. Pawlik, MD, of The Ohio State University, Columbus, and colleagues. A cancer diagnosis can cause not only physical stress, but mental, emotional, social, and economic stress that can prompt a new BHD, cause relapse of a previous BHD, or exacerbate a current BHD, the researchers noted.
What is Known About BHDs and Cancer?
Although previous studies have shown a possible association between BHDs and increased cancer risk, as well as reduced compliance with care, the effect of BHDs on outcomes in cancer patients undergoing surgical resection has not been examined, wrote Dr. Pawlik and colleagues.
Previous research has focused on the impact of having a preexisting serious mental illness (SMI) such as schizophrenia and bipolar disorder on cancer care.
A 2023 literature review of 27 studies published in the Journal of Medical Imaging and Radiation Sciences showed that patients with preexisting severe mental illness (such as schizophrenia or bipolar disorder) had greater cancer-related mortality. In that study, the researchers also found that patients with severe mental illness were more likely to have metastatic disease at diagnosis, but less likely to receive optimal treatments, than individuals without SMIs.
Many studies also have focused on patients developing mental health problems (including BHDs) after a cancer diagnosis, but the current study is the first known to examine outcomes in those with BHDs before cancer.
Why Was It Important to Conduct This Study?
“BHDs are a diverse set of mental illnesses that affect an individual’s psychosocial wellbeing, potentially resulting in maladaptive behaviors,” Dr. Pawlik said in an interview. BHDs, which include substance abuse, eating disorders, and sleep disorders, are less common than anxiety/depression, but have an estimated prevalence of 1.3%-3.1% among adults in the United States, he said.
What Does the New Study Add?
In the new review by Dr. Pawlik and colleagues, published in the Journal of the American College of Surgeons (Katayama ES. J Am Coll Surg. 2024 Feb 29. doi: 2024. 10.1097/XCS.0000000000000954), BHDs were defined as substance abuse, eating disorders, or sleep disorders, which had not been the focus of previous studies. The researchers reviewed data from 694,836 adult patients with lung, esophageal, gastric, liver, pancreatic, or colorectal cancer between 2018-2021 using the Medicare Standard Analytic files. A total of 46,719 patients (6.7%) had at least one BHD.
Overall, patients with a BHD were significantly less likely than those without a BHD to undergo surgical resection (20.3% vs. 23.4%). Patients with a BHD also had significantly worse long-term postoperative survival than those without BHDs (median 37.1 months vs. 46.6 months) and significantly higher in-hospital costs ($17,432 vs. 16,159, P less than .001 for all).
Among patients who underwent cancer surgery, the odds of any complication were significantly higher for those with a BHD compared to those with no BHD (odds ratio 1.32), as were the odds of a prolonged length of stay (OR 1.67) and 90-day readmission (OR 1.57).
Dr. Pawlik said he was surprised by several of the findings, including that 1 in 15 Medicare beneficiaries had a BHD diagnosis, “with male sex and minority racial status, as well as higher social vulnerability, being associated with a higher prevalence of BHD.”
Also, the independent association of having a BHD with 30%-50% higher odds of a complication, prolonged length of stay, and 90-day readmission was higher than Dr. Pawlik had anticipated.
Why Do Patients With BHDs Have Fewer Surgeries and Worse Outcomes?
The reasons for this association were likely multifactorial and may reflect the greater burden of medical comorbidity and chronic illness in many patients with BHDs because of maladaptive lifestyles or poor nutrition status, Dr. Pawlik said.
“Patients with BHDs also likely face barriers to accessing care, which was noted particularly among patients with BHDs who lived in socially vulnerable areas,” he said. BHD patients also were more likely to be treated at low-volume rather than high-volume hospitals, “which undoubtedly contributed in part to worse outcomes in this cohort of patients,” he added.
What Can Oncologists Do to Help?
The take-home message for clinicians is that BHDs are linked to worse surgical outcomes and higher health care costs in cancer patients, Dr. Pawlik said in an interview.
“Enhanced accessibility to behavioral healthcare, as well as comprehensive policy reform related to mental health services are needed to improve care of patients with BHDs,” he said. “For example, implementing psychiatry compensation programs may encourage practice in vulnerable areas,” he said.
Other strategies include a following a collaborative care model involving mental health professionals working in tandem with primary care and mid-level practitioners and increasing use and establishment of telehealth systems to improve patient access to BHD services, he said.
What Are the Limitations?
The study by Dr. Pawlik and colleagues was limited by several factors, including the lack of data on younger patients and the full range of BHDs, as well as underreporting of BHDs and the high copays for mental health care, the researchers noted. However, the results suggest that concomitant BHDs are associated with worse cancer outcomes and higher in-hospital costs, and illustrate the need to screen for and target these conditions in cancer patients, the researchers concluded.
What Are the Next Steps for Research?
The current study involved Medicare beneficiaries aged 65 years or older, and more research is needed to investigate the impact of BHDs among younger cancer patients in whom the prevalence may be higher and the impact of BHDs may be different, Dr. Pawlik said in an interview. In addition, the analysis of BHDs as a composite of substance abuse, eating disorders, and sleep disorders (because the numbers were too small to break out data for each disorder, separately) prevented investigation of potential differences and unique challenges faced by distinct subpopulations of BHD patients, he said.
“Future studies should examine the individual impact of substance abuse, eating disorders, and sleep disorders on access to surgery, as well as the potential different impact that each one of these different BHDs may have on postoperative outcomes,” Dr. Pawlik suggested.
The study was supported by The Ohio State University College of Medicine Roessler Summer Research Scholarship. The researchers had no financial conflicts to disclose.
FROM JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
New Trials in Leukemia and Lymphoma: Could Your Patient Benefit?
Several clinical trials in leukemia and lymphoma have started enrolling recently. Maybe one of your patients could benefit from taking part?
run by the Center for International Blood and Bone Marrow Transplant Research.
The purpose of the study is to test whether cyclophosphamide, which is given to prevent a dreaded complication of stem cell transplantation called graft-versus-host disease, can be safely reduced without increasing infection or reducing protection. All participants will receive cyclophosphamide on days 3 and 4 post transplant. One group will receive a reduced dose of cyclophosphamide (25 mg/kg per dose), and the other will be given a usual dose (37.5 mg/kg).
Sites in Michigan, Missouri, Oregon, Virginia, and Washington started recruiting for 190 participants in December 2023. Study centers in Florida, Massachusetts, New York, and Wisconsin are also planned. Infection-free survival is the primary endpoint, and overall survival is a secondary measure. Quality of life (QoL) is not recorded. More details at clinicaltrials.gov.
Untreated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Adults who are newly diagnosed with this type of cancer and have active disease may wish to consider a randomized, open-label, phase 3 trial testing an experimental Bruton tyrosine kinase (BTK) inhibitor, nemtabrutinib (from Merck Sharp & Dohme), against standard-of-care BTK inhibitors ibrutinib (Imbruvica) and acalabrutinib (Calquence).
BTK inhibitors target B-cell proliferation in B-cell cancers such as CLL/SLL and allow for chemotherapy-free treatment of some hematological malignancies. In this study, until disease progression, unacceptable toxicity, or another reason for discontinuation occurs, participants will take daily oral nemtabrutinib, ibrutinib, or acalabrutinib.
The study opened in December 2023 in Pennsylvania, Washington, Taiwan, Israel, and the United Kingdom seeking 1200 participants. The primary outcomes are objective response rate and progression-free survival. Overall survival is a secondary outcome, and QoL is not measured. More details at clinicaltrials.gov.
Relapsed or refractory leukemia with a KMT2A-gene rearrangement (KMT2A-r). Children aged 1 month to younger than 6 years with this diagnosis may be able to join an open-label, nonrandomized, Children’s Oncology Group phase 2 study to determine the most tolerable and/or effective dose of an experimental oral drug called revumenib when added to chemotherapy.
KMT2A-gene alterations are associated with a poor prognosis in leukemia. These alterations cause blood cells to dedifferentiate and start proliferating uncontrollably as leukemia cells. The expression of the damaged KMT2A gene relies on a protein called menin. Revumenib, from Syndax Pharmaceuticals, blocks menin and prevents expression of KMT2A.
Children in the study will receive two different regimens of revumenib in combination with chemotherapy for up to a year, or until disease progression or unacceptable toxicity, and will then be followed for up to 5 years. Trial centers in 12 US states opened their doors in January 2024 looking for 78 participants. Toxicities and minimal residual disease are the primary outcomes; overall survival is a secondary outcome, and QoL is not assessed. More details at clinicaltrials.gov.
Previously untreated follicular lymphoma or diffuse large B-cell lymphoma. Adults with one of these types of lymphoma may be eligible for one of three open-label, randomized, phase 3 trials testing odronextamab (from Regeneron). This bispecific antibody is designed to ‘lock together’ CD20 on cancer cells with CD3-expressing cancer-killing T cells. It has shown anti-lymphoma activity in heavily pretreated patients.
Late in 2023, three phase 3 trials turned the spotlight on treatment-naive patients and started recruiting 2115 participants to assess odronextamab in this setting. The trial OLYMPIA-1 will compare odronextamab with standard-of-care rituximab (Rituxan) plus chemotherapy in follicular lymphoma. OLYMPIA-2 will test the drug in combination with chemotherapy, also in follicular lymphoma. OLYMPIA-3 will evaluate odronextamab plus chemotherapy against rituximab and chemotherapy in people with large B-cell lymphoma.
All study drugs, including odronextamab, will be administered by intravenous infusion, and participants will be followed for up to 5 years. Research centers across eight US states and Australia, Czechia, France, Italy, Poland, Spain, Turkey, and Thailand are currently accepting participants for the three trials. The primary outcomes are various measures of toxicity and complete response at 30 months in the follicular lymphoma studies and toxicity and progression-free survival in large B-cell lymphoma. All three trials are measuring overall survival and QoL as secondary endpoints.
Previously untreated stage II, III, or IV follicular lymphoma. Adults with this type of cancer may be eligible to participate in a randomized, open-label, phase 3 study testing whether an experimental therapy called epcoritamab (from AbbVie) improves disease response and is tolerable when added to standard therapy. For up to 120 weeks, one group of participants will receive a combination of intravenous rituximab and oral lenalidomide (Revlimid), while a second group will also receive subcutaneous injections of epcoritamab. Some participants may be offered investigators’ choice of chemotherapy as well.
Sites across Iowa, Maryland, Missouri, Ohio, Washington, and Montana started welcoming their 900 participants in February 2024. The primary outcome is complete response at 30 months. Overall survival and QoL are secondary outcomes. More details at clinicaltrials.gov.
Relapsed or refractory mantle cell lymphoma. Adults facing one of these clinical scenarios can join an Academic and Community Cancer Research United open label, phase 2 trial examining the effectiveness of combining tafasitamab (Monjuvi), lenalidomide, and venetoclax (Venclexta) for such patients.
Frontline therapy does not cure mantle cell lymphoma, and continued relapses are common. In this situation, treatments can include acalabrutinib, ibrutinib, stem cell transplantation, venetoclax, lenalidomide, and rituximab.
In this study, participants will take venetoclax and lenalidomide daily and receive intravenous tafasitamab every 2 weeks after an initial ramp-up period as per clinic standards. Participants will be followed for 5 years after entering the trial. The Mayo Clinic in Rochester, Minnesota, began recruiting the planned 100 trial participants in January 2024. The primary outcome is objective response rate; overall survival is a secondary outcome, and QoL will not be tracked. More details at clinicaltrials.gov.
All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).
A version of this article appeared on Medscape.com .
Several clinical trials in leukemia and lymphoma have started enrolling recently. Maybe one of your patients could benefit from taking part?
run by the Center for International Blood and Bone Marrow Transplant Research.
The purpose of the study is to test whether cyclophosphamide, which is given to prevent a dreaded complication of stem cell transplantation called graft-versus-host disease, can be safely reduced without increasing infection or reducing protection. All participants will receive cyclophosphamide on days 3 and 4 post transplant. One group will receive a reduced dose of cyclophosphamide (25 mg/kg per dose), and the other will be given a usual dose (37.5 mg/kg).
Sites in Michigan, Missouri, Oregon, Virginia, and Washington started recruiting for 190 participants in December 2023. Study centers in Florida, Massachusetts, New York, and Wisconsin are also planned. Infection-free survival is the primary endpoint, and overall survival is a secondary measure. Quality of life (QoL) is not recorded. More details at clinicaltrials.gov.
Untreated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Adults who are newly diagnosed with this type of cancer and have active disease may wish to consider a randomized, open-label, phase 3 trial testing an experimental Bruton tyrosine kinase (BTK) inhibitor, nemtabrutinib (from Merck Sharp & Dohme), against standard-of-care BTK inhibitors ibrutinib (Imbruvica) and acalabrutinib (Calquence).
BTK inhibitors target B-cell proliferation in B-cell cancers such as CLL/SLL and allow for chemotherapy-free treatment of some hematological malignancies. In this study, until disease progression, unacceptable toxicity, or another reason for discontinuation occurs, participants will take daily oral nemtabrutinib, ibrutinib, or acalabrutinib.
The study opened in December 2023 in Pennsylvania, Washington, Taiwan, Israel, and the United Kingdom seeking 1200 participants. The primary outcomes are objective response rate and progression-free survival. Overall survival is a secondary outcome, and QoL is not measured. More details at clinicaltrials.gov.
Relapsed or refractory leukemia with a KMT2A-gene rearrangement (KMT2A-r). Children aged 1 month to younger than 6 years with this diagnosis may be able to join an open-label, nonrandomized, Children’s Oncology Group phase 2 study to determine the most tolerable and/or effective dose of an experimental oral drug called revumenib when added to chemotherapy.
KMT2A-gene alterations are associated with a poor prognosis in leukemia. These alterations cause blood cells to dedifferentiate and start proliferating uncontrollably as leukemia cells. The expression of the damaged KMT2A gene relies on a protein called menin. Revumenib, from Syndax Pharmaceuticals, blocks menin and prevents expression of KMT2A.
Children in the study will receive two different regimens of revumenib in combination with chemotherapy for up to a year, or until disease progression or unacceptable toxicity, and will then be followed for up to 5 years. Trial centers in 12 US states opened their doors in January 2024 looking for 78 participants. Toxicities and minimal residual disease are the primary outcomes; overall survival is a secondary outcome, and QoL is not assessed. More details at clinicaltrials.gov.
Previously untreated follicular lymphoma or diffuse large B-cell lymphoma. Adults with one of these types of lymphoma may be eligible for one of three open-label, randomized, phase 3 trials testing odronextamab (from Regeneron). This bispecific antibody is designed to ‘lock together’ CD20 on cancer cells with CD3-expressing cancer-killing T cells. It has shown anti-lymphoma activity in heavily pretreated patients.
Late in 2023, three phase 3 trials turned the spotlight on treatment-naive patients and started recruiting 2115 participants to assess odronextamab in this setting. The trial OLYMPIA-1 will compare odronextamab with standard-of-care rituximab (Rituxan) plus chemotherapy in follicular lymphoma. OLYMPIA-2 will test the drug in combination with chemotherapy, also in follicular lymphoma. OLYMPIA-3 will evaluate odronextamab plus chemotherapy against rituximab and chemotherapy in people with large B-cell lymphoma.
All study drugs, including odronextamab, will be administered by intravenous infusion, and participants will be followed for up to 5 years. Research centers across eight US states and Australia, Czechia, France, Italy, Poland, Spain, Turkey, and Thailand are currently accepting participants for the three trials. The primary outcomes are various measures of toxicity and complete response at 30 months in the follicular lymphoma studies and toxicity and progression-free survival in large B-cell lymphoma. All three trials are measuring overall survival and QoL as secondary endpoints.
Previously untreated stage II, III, or IV follicular lymphoma. Adults with this type of cancer may be eligible to participate in a randomized, open-label, phase 3 study testing whether an experimental therapy called epcoritamab (from AbbVie) improves disease response and is tolerable when added to standard therapy. For up to 120 weeks, one group of participants will receive a combination of intravenous rituximab and oral lenalidomide (Revlimid), while a second group will also receive subcutaneous injections of epcoritamab. Some participants may be offered investigators’ choice of chemotherapy as well.
Sites across Iowa, Maryland, Missouri, Ohio, Washington, and Montana started welcoming their 900 participants in February 2024. The primary outcome is complete response at 30 months. Overall survival and QoL are secondary outcomes. More details at clinicaltrials.gov.
Relapsed or refractory mantle cell lymphoma. Adults facing one of these clinical scenarios can join an Academic and Community Cancer Research United open label, phase 2 trial examining the effectiveness of combining tafasitamab (Monjuvi), lenalidomide, and venetoclax (Venclexta) for such patients.
Frontline therapy does not cure mantle cell lymphoma, and continued relapses are common. In this situation, treatments can include acalabrutinib, ibrutinib, stem cell transplantation, venetoclax, lenalidomide, and rituximab.
In this study, participants will take venetoclax and lenalidomide daily and receive intravenous tafasitamab every 2 weeks after an initial ramp-up period as per clinic standards. Participants will be followed for 5 years after entering the trial. The Mayo Clinic in Rochester, Minnesota, began recruiting the planned 100 trial participants in January 2024. The primary outcome is objective response rate; overall survival is a secondary outcome, and QoL will not be tracked. More details at clinicaltrials.gov.
All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).
A version of this article appeared on Medscape.com .
Several clinical trials in leukemia and lymphoma have started enrolling recently. Maybe one of your patients could benefit from taking part?
run by the Center for International Blood and Bone Marrow Transplant Research.
The purpose of the study is to test whether cyclophosphamide, which is given to prevent a dreaded complication of stem cell transplantation called graft-versus-host disease, can be safely reduced without increasing infection or reducing protection. All participants will receive cyclophosphamide on days 3 and 4 post transplant. One group will receive a reduced dose of cyclophosphamide (25 mg/kg per dose), and the other will be given a usual dose (37.5 mg/kg).
Sites in Michigan, Missouri, Oregon, Virginia, and Washington started recruiting for 190 participants in December 2023. Study centers in Florida, Massachusetts, New York, and Wisconsin are also planned. Infection-free survival is the primary endpoint, and overall survival is a secondary measure. Quality of life (QoL) is not recorded. More details at clinicaltrials.gov.
Untreated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Adults who are newly diagnosed with this type of cancer and have active disease may wish to consider a randomized, open-label, phase 3 trial testing an experimental Bruton tyrosine kinase (BTK) inhibitor, nemtabrutinib (from Merck Sharp & Dohme), against standard-of-care BTK inhibitors ibrutinib (Imbruvica) and acalabrutinib (Calquence).
BTK inhibitors target B-cell proliferation in B-cell cancers such as CLL/SLL and allow for chemotherapy-free treatment of some hematological malignancies. In this study, until disease progression, unacceptable toxicity, or another reason for discontinuation occurs, participants will take daily oral nemtabrutinib, ibrutinib, or acalabrutinib.
The study opened in December 2023 in Pennsylvania, Washington, Taiwan, Israel, and the United Kingdom seeking 1200 participants. The primary outcomes are objective response rate and progression-free survival. Overall survival is a secondary outcome, and QoL is not measured. More details at clinicaltrials.gov.
Relapsed or refractory leukemia with a KMT2A-gene rearrangement (KMT2A-r). Children aged 1 month to younger than 6 years with this diagnosis may be able to join an open-label, nonrandomized, Children’s Oncology Group phase 2 study to determine the most tolerable and/or effective dose of an experimental oral drug called revumenib when added to chemotherapy.
KMT2A-gene alterations are associated with a poor prognosis in leukemia. These alterations cause blood cells to dedifferentiate and start proliferating uncontrollably as leukemia cells. The expression of the damaged KMT2A gene relies on a protein called menin. Revumenib, from Syndax Pharmaceuticals, blocks menin and prevents expression of KMT2A.
Children in the study will receive two different regimens of revumenib in combination with chemotherapy for up to a year, or until disease progression or unacceptable toxicity, and will then be followed for up to 5 years. Trial centers in 12 US states opened their doors in January 2024 looking for 78 participants. Toxicities and minimal residual disease are the primary outcomes; overall survival is a secondary outcome, and QoL is not assessed. More details at clinicaltrials.gov.
Previously untreated follicular lymphoma or diffuse large B-cell lymphoma. Adults with one of these types of lymphoma may be eligible for one of three open-label, randomized, phase 3 trials testing odronextamab (from Regeneron). This bispecific antibody is designed to ‘lock together’ CD20 on cancer cells with CD3-expressing cancer-killing T cells. It has shown anti-lymphoma activity in heavily pretreated patients.
Late in 2023, three phase 3 trials turned the spotlight on treatment-naive patients and started recruiting 2115 participants to assess odronextamab in this setting. The trial OLYMPIA-1 will compare odronextamab with standard-of-care rituximab (Rituxan) plus chemotherapy in follicular lymphoma. OLYMPIA-2 will test the drug in combination with chemotherapy, also in follicular lymphoma. OLYMPIA-3 will evaluate odronextamab plus chemotherapy against rituximab and chemotherapy in people with large B-cell lymphoma.
All study drugs, including odronextamab, will be administered by intravenous infusion, and participants will be followed for up to 5 years. Research centers across eight US states and Australia, Czechia, France, Italy, Poland, Spain, Turkey, and Thailand are currently accepting participants for the three trials. The primary outcomes are various measures of toxicity and complete response at 30 months in the follicular lymphoma studies and toxicity and progression-free survival in large B-cell lymphoma. All three trials are measuring overall survival and QoL as secondary endpoints.
Previously untreated stage II, III, or IV follicular lymphoma. Adults with this type of cancer may be eligible to participate in a randomized, open-label, phase 3 study testing whether an experimental therapy called epcoritamab (from AbbVie) improves disease response and is tolerable when added to standard therapy. For up to 120 weeks, one group of participants will receive a combination of intravenous rituximab and oral lenalidomide (Revlimid), while a second group will also receive subcutaneous injections of epcoritamab. Some participants may be offered investigators’ choice of chemotherapy as well.
Sites across Iowa, Maryland, Missouri, Ohio, Washington, and Montana started welcoming their 900 participants in February 2024. The primary outcome is complete response at 30 months. Overall survival and QoL are secondary outcomes. More details at clinicaltrials.gov.
Relapsed or refractory mantle cell lymphoma. Adults facing one of these clinical scenarios can join an Academic and Community Cancer Research United open label, phase 2 trial examining the effectiveness of combining tafasitamab (Monjuvi), lenalidomide, and venetoclax (Venclexta) for such patients.
Frontline therapy does not cure mantle cell lymphoma, and continued relapses are common. In this situation, treatments can include acalabrutinib, ibrutinib, stem cell transplantation, venetoclax, lenalidomide, and rituximab.
In this study, participants will take venetoclax and lenalidomide daily and receive intravenous tafasitamab every 2 weeks after an initial ramp-up period as per clinic standards. Participants will be followed for 5 years after entering the trial. The Mayo Clinic in Rochester, Minnesota, began recruiting the planned 100 trial participants in January 2024. The primary outcome is objective response rate; overall survival is a secondary outcome, and QoL will not be tracked. More details at clinicaltrials.gov.
All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).
A version of this article appeared on Medscape.com .
AML: Genetic Testing Unlocks Hope
For adult patients, “we’ve seen a series of remarkable and well-overdue advances in a space that had not changed much over the prior decades,” hematologist/oncologist Thomas William LeBlanc, MD, associate professor of medicine at Duke University School of Medicine, Durham, North Carolina, said in an interview.
According to the National Cancer Institute, AML will be newly diagnosed in 20,800 patients in 2024, at a median age of 69, and will cause 11,220 deaths. As many as 70% of adult patients will reach complete remission, and 45% of those will live for more than 3 years and potentially be cured. As for children, the Leukemia & Lymphoma Society says the 5-year survival rate from 2012-2018 was 69% for those under 15 years old.
As the American Cancer Society notes, the goal of AML treatment “is to put the leukemia into complete remission (the bone marrow and blood cell counts return to normal), preferably a complete molecular remission (no signs of leukemia in the bone marrow, even using sensitive lab tests), and to keep it that way.”
Chemotherapy Strategies Shift Over Time
In terms of the treatment of adults with AML, “targeted therapies, in addition to the expanding role of venetoclax, has really altered our approach to AML from diagnosis, including after relapse, and later in the disease,” hematologist/oncologist Andrew M. Brunner, MD, of Harvard Medical School and Massachusetts General Hospital, Boston, said in an interview. “The ability to explore these options as monotherapy and in novel combinations has dramatically expanded our treatment options.”
Much depends on the underlying genetic profile of the disease, he said. “There certainly have been gains in patient survival in AML, but those improvements remain fairly heterogeneous and dependent on the underlying genetic profile of the disease. For instance, advances in FLT3- and IDH1/2-mutated AML are a direct result of the improvements in targeted therapies directed at these mutations. Similarly, some molecular and cytogenetic subtypes of AML are particularly responsive to venetoclax-based regimens, and these regimens have been expanded to previously undertreated populations, particularly those over age 60.”
Specifically, Dr. LeBlanc said, the Food and Drug Administration has approved “3 different FLT3 inhibitors, 2 IDH1 inhibitors, 1 IDH2 inhibitor, a BCL-2 inhibitor, a smoothened/hedgehog pathway inhibitor, an oral maintenance chemotherapy/hypomethylating agent (CC-486/oral azacitidine), a CD33-targeting antibody-drug conjugate, and even a novel formulation of two older chemotherapies that improves efficacy in a poor prognosis subgroup (CPX-351/liposomal daunorubicin and cytarabine).”
There’s also been a shift in treatment protocols for patients who were not fit for intensive chemotherapy. In the past, he said, it was standard “to give single-agent hypomethylating chemotherapy with azacitidine or decitabine, or in some contexts, low-dose chemotherapy with cytarabine. Today, many patients who are older and/or more frail are receiving novel therapies either alone or in combination, with greater efficacy and longer duration of response than previously seen with chemotherapy alone.”
Outcomes Improve but Remain Grim in High-Risk Cases
As a result, Dr. LeBlanc said, “we’re definitely seeing much better outcomes in AML overall. It takes some time to prove this via outcomes data assessments in a large population, but I expect that registries will show significant improvements in overall survival in the coming years, owing to the many new FDA approvals in AML”
Dr. LeBlanc highlighted national data from 2013-2019 showing that the 5-year relative survival rate from AML is 31.7%. That’s up from 26% just a few years ago, and the numbers “always lag several years behind the current year of practice,” he said. However, “the major area where we still have relatively poor outcomes and significant unmet needs remains the ‘adverse risk’ group of patients, particularly those who are older and/or not candidates for hematopoietic stem cell transplantation, which generally is the only potentially curative option for adverse-risk AML.”
He went on to say that “this risk grouping includes those with TP53 mutations, most of which confer a particularly poor prognosis. Exciting therapies that many of us were hoping would prove effective in this subgroup have unfortunately failed in recent clinical trials. We still have a lot of work to do in adverse-risk AML particularly, and also for those whose leukemia has relapsed.”
Mikkael Sekeres, MD, MS, chief of the Division of Hematology at the University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, agreed that more progress is needed, since survival rates are low even as lifespans improve. One key will be “better identifying subtypes of acute myeloid leukemia, and identifying the therapies that will benefit those people most,” he said in an interview. On the other side, it’s important to identify “when aggressive therapies aren’t going to work in somebody and maybe turn toward less-aggressive approaches so we can maximize that person’s quality of life.”
What advice do AML experts have for their colleagues? Dr. LeBlanc said “older patients are not often enough considered for allogeneic stem cell transplantation, which could potentially cure their AML when given as a consolidation treatment for those in remission. I have several patients who are healthy and in their 70s who have enormously benefited from transplants and are now being several years out from transplant with adverse risk AML and without relapse. They’ve had no significant impairments of their quality of life, including no significant graft vs. host disease.”
Dr. Sekeres highlighted the American Society of Hematology’s guidelines for treating older adults with AML, which are currently being updated. It’s crucial to order genetic testing “up front,” he said. “I’m often pleasantly surprised when genetic testing returns and reveals that I have other treatment options.”
However, it’s crucial to understand a patient’s priorities. “I’ve had patients who are 75 who say to me, ‘Do everything under the sun to get rid of my leukemia, I want to live as long as possible.’ And I’ve had patients who say, ‘I want to see as little of doctors and nurses as I can. I want you to maximize my quality of life and keep me out of the hospital.’ ”
Dr. Sekeres also noted that insurers may not cover some pill-based AML treatments such as venetoclax. “We work with our patients and assistance programs. For the most part, we’re pretty successful at getting these drugs for our patients,” he said.
In Pediatrics, Clinical Trials Are Crucial
AML in children is less well-known than in adults, since the number of cases is so small. The disease is diagnosed in about 500 children a year in the United States, according to St. Jude Children’s Research Hospital, adding, however, that AML is “the most common second cancer among children treated for other cancers.”
AML in children gained attention earlier this year when the 2-year-old daughter of a Boston Herald NFL reporter died of the disease following a bone marrow transplant and chemotherapy. Despite the agonies of her treatment, reporter Doug Kyed told a reporter that his daughter Hallie “was still able to find joy every day.”
In an interview, hematologist/oncologist Sarah K. Tasian, MD, of Children’s Hospital of Philadelphia, said researchers are discovering that pediatric AML is significantly different on from a biological perspective from adult AML. “We’ve come to understand a lot more about who these patients are, what makes these leukemias tick, and what their Achilles’ heels are. Then we can align that with the clinical trials outcome data that we have.”
About 80%-90% of pediatric patients with AML nationwide are enrolled in clinical trials, Dr. Tasian said, and an international consortium called the Children’s Oncology Group gathers data about genetics. About 60%-70% of patients will be cured, she added.
However, “we’ve kind of been stuck for about the last 20 years,” she said. “A lot of improving the survival of patients has not been because we’ve been better at chemotherapy or using new chemo, but because we’ve gotten better at supportive care, at treating infections that can be fatal.”
There haven’t been major conflicts with insurers over coverage, she said, although drug shortages are a problem, especially in relapsed AML.
As for advice to colleagues, Dr. Tasian counseled them to understand the importance of genetic testing and the expanding role of stem cell transplants. “We are now transplanting somewhere between 30% and 50% of children with AML, which is a higher rate than we used to do,” she said. The number is up thanks to genetic testing that reveals which patients are most likely to benefit.
Also, she noted, “the chemotherapy that we get to these patients is really strong, and patients have a lot of complications. Really pay attention to supportive care.”
Dr. LeBlanc reported ties with AbbVie, Agios/Servier, Astellas, BMS/Celgene, Genentech, Pfizer, Incyte, Rige, Deverra, GSK, Jazz, and Seattle Genetics. Dr. Sekeres discloses relationships with BMS and Kurome. Dr. Tasian serves as the Leukemia & Lymphoma Society Pediatric Acute Leukemia consortium clinical trials leader and works with pharmaceutical companies on clinical trials under confidentiality agreements. Dr. Brunner has no disclosures.
For adult patients, “we’ve seen a series of remarkable and well-overdue advances in a space that had not changed much over the prior decades,” hematologist/oncologist Thomas William LeBlanc, MD, associate professor of medicine at Duke University School of Medicine, Durham, North Carolina, said in an interview.
According to the National Cancer Institute, AML will be newly diagnosed in 20,800 patients in 2024, at a median age of 69, and will cause 11,220 deaths. As many as 70% of adult patients will reach complete remission, and 45% of those will live for more than 3 years and potentially be cured. As for children, the Leukemia & Lymphoma Society says the 5-year survival rate from 2012-2018 was 69% for those under 15 years old.
As the American Cancer Society notes, the goal of AML treatment “is to put the leukemia into complete remission (the bone marrow and blood cell counts return to normal), preferably a complete molecular remission (no signs of leukemia in the bone marrow, even using sensitive lab tests), and to keep it that way.”
Chemotherapy Strategies Shift Over Time
In terms of the treatment of adults with AML, “targeted therapies, in addition to the expanding role of venetoclax, has really altered our approach to AML from diagnosis, including after relapse, and later in the disease,” hematologist/oncologist Andrew M. Brunner, MD, of Harvard Medical School and Massachusetts General Hospital, Boston, said in an interview. “The ability to explore these options as monotherapy and in novel combinations has dramatically expanded our treatment options.”
Much depends on the underlying genetic profile of the disease, he said. “There certainly have been gains in patient survival in AML, but those improvements remain fairly heterogeneous and dependent on the underlying genetic profile of the disease. For instance, advances in FLT3- and IDH1/2-mutated AML are a direct result of the improvements in targeted therapies directed at these mutations. Similarly, some molecular and cytogenetic subtypes of AML are particularly responsive to venetoclax-based regimens, and these regimens have been expanded to previously undertreated populations, particularly those over age 60.”
Specifically, Dr. LeBlanc said, the Food and Drug Administration has approved “3 different FLT3 inhibitors, 2 IDH1 inhibitors, 1 IDH2 inhibitor, a BCL-2 inhibitor, a smoothened/hedgehog pathway inhibitor, an oral maintenance chemotherapy/hypomethylating agent (CC-486/oral azacitidine), a CD33-targeting antibody-drug conjugate, and even a novel formulation of two older chemotherapies that improves efficacy in a poor prognosis subgroup (CPX-351/liposomal daunorubicin and cytarabine).”
There’s also been a shift in treatment protocols for patients who were not fit for intensive chemotherapy. In the past, he said, it was standard “to give single-agent hypomethylating chemotherapy with azacitidine or decitabine, or in some contexts, low-dose chemotherapy with cytarabine. Today, many patients who are older and/or more frail are receiving novel therapies either alone or in combination, with greater efficacy and longer duration of response than previously seen with chemotherapy alone.”
Outcomes Improve but Remain Grim in High-Risk Cases
As a result, Dr. LeBlanc said, “we’re definitely seeing much better outcomes in AML overall. It takes some time to prove this via outcomes data assessments in a large population, but I expect that registries will show significant improvements in overall survival in the coming years, owing to the many new FDA approvals in AML”
Dr. LeBlanc highlighted national data from 2013-2019 showing that the 5-year relative survival rate from AML is 31.7%. That’s up from 26% just a few years ago, and the numbers “always lag several years behind the current year of practice,” he said. However, “the major area where we still have relatively poor outcomes and significant unmet needs remains the ‘adverse risk’ group of patients, particularly those who are older and/or not candidates for hematopoietic stem cell transplantation, which generally is the only potentially curative option for adverse-risk AML.”
He went on to say that “this risk grouping includes those with TP53 mutations, most of which confer a particularly poor prognosis. Exciting therapies that many of us were hoping would prove effective in this subgroup have unfortunately failed in recent clinical trials. We still have a lot of work to do in adverse-risk AML particularly, and also for those whose leukemia has relapsed.”
Mikkael Sekeres, MD, MS, chief of the Division of Hematology at the University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, agreed that more progress is needed, since survival rates are low even as lifespans improve. One key will be “better identifying subtypes of acute myeloid leukemia, and identifying the therapies that will benefit those people most,” he said in an interview. On the other side, it’s important to identify “when aggressive therapies aren’t going to work in somebody and maybe turn toward less-aggressive approaches so we can maximize that person’s quality of life.”
What advice do AML experts have for their colleagues? Dr. LeBlanc said “older patients are not often enough considered for allogeneic stem cell transplantation, which could potentially cure their AML when given as a consolidation treatment for those in remission. I have several patients who are healthy and in their 70s who have enormously benefited from transplants and are now being several years out from transplant with adverse risk AML and without relapse. They’ve had no significant impairments of their quality of life, including no significant graft vs. host disease.”
Dr. Sekeres highlighted the American Society of Hematology’s guidelines for treating older adults with AML, which are currently being updated. It’s crucial to order genetic testing “up front,” he said. “I’m often pleasantly surprised when genetic testing returns and reveals that I have other treatment options.”
However, it’s crucial to understand a patient’s priorities. “I’ve had patients who are 75 who say to me, ‘Do everything under the sun to get rid of my leukemia, I want to live as long as possible.’ And I’ve had patients who say, ‘I want to see as little of doctors and nurses as I can. I want you to maximize my quality of life and keep me out of the hospital.’ ”
Dr. Sekeres also noted that insurers may not cover some pill-based AML treatments such as venetoclax. “We work with our patients and assistance programs. For the most part, we’re pretty successful at getting these drugs for our patients,” he said.
In Pediatrics, Clinical Trials Are Crucial
AML in children is less well-known than in adults, since the number of cases is so small. The disease is diagnosed in about 500 children a year in the United States, according to St. Jude Children’s Research Hospital, adding, however, that AML is “the most common second cancer among children treated for other cancers.”
AML in children gained attention earlier this year when the 2-year-old daughter of a Boston Herald NFL reporter died of the disease following a bone marrow transplant and chemotherapy. Despite the agonies of her treatment, reporter Doug Kyed told a reporter that his daughter Hallie “was still able to find joy every day.”
In an interview, hematologist/oncologist Sarah K. Tasian, MD, of Children’s Hospital of Philadelphia, said researchers are discovering that pediatric AML is significantly different on from a biological perspective from adult AML. “We’ve come to understand a lot more about who these patients are, what makes these leukemias tick, and what their Achilles’ heels are. Then we can align that with the clinical trials outcome data that we have.”
About 80%-90% of pediatric patients with AML nationwide are enrolled in clinical trials, Dr. Tasian said, and an international consortium called the Children’s Oncology Group gathers data about genetics. About 60%-70% of patients will be cured, she added.
However, “we’ve kind of been stuck for about the last 20 years,” she said. “A lot of improving the survival of patients has not been because we’ve been better at chemotherapy or using new chemo, but because we’ve gotten better at supportive care, at treating infections that can be fatal.”
There haven’t been major conflicts with insurers over coverage, she said, although drug shortages are a problem, especially in relapsed AML.
As for advice to colleagues, Dr. Tasian counseled them to understand the importance of genetic testing and the expanding role of stem cell transplants. “We are now transplanting somewhere between 30% and 50% of children with AML, which is a higher rate than we used to do,” she said. The number is up thanks to genetic testing that reveals which patients are most likely to benefit.
Also, she noted, “the chemotherapy that we get to these patients is really strong, and patients have a lot of complications. Really pay attention to supportive care.”
Dr. LeBlanc reported ties with AbbVie, Agios/Servier, Astellas, BMS/Celgene, Genentech, Pfizer, Incyte, Rige, Deverra, GSK, Jazz, and Seattle Genetics. Dr. Sekeres discloses relationships with BMS and Kurome. Dr. Tasian serves as the Leukemia & Lymphoma Society Pediatric Acute Leukemia consortium clinical trials leader and works with pharmaceutical companies on clinical trials under confidentiality agreements. Dr. Brunner has no disclosures.
For adult patients, “we’ve seen a series of remarkable and well-overdue advances in a space that had not changed much over the prior decades,” hematologist/oncologist Thomas William LeBlanc, MD, associate professor of medicine at Duke University School of Medicine, Durham, North Carolina, said in an interview.
According to the National Cancer Institute, AML will be newly diagnosed in 20,800 patients in 2024, at a median age of 69, and will cause 11,220 deaths. As many as 70% of adult patients will reach complete remission, and 45% of those will live for more than 3 years and potentially be cured. As for children, the Leukemia & Lymphoma Society says the 5-year survival rate from 2012-2018 was 69% for those under 15 years old.
As the American Cancer Society notes, the goal of AML treatment “is to put the leukemia into complete remission (the bone marrow and blood cell counts return to normal), preferably a complete molecular remission (no signs of leukemia in the bone marrow, even using sensitive lab tests), and to keep it that way.”
Chemotherapy Strategies Shift Over Time
In terms of the treatment of adults with AML, “targeted therapies, in addition to the expanding role of venetoclax, has really altered our approach to AML from diagnosis, including after relapse, and later in the disease,” hematologist/oncologist Andrew M. Brunner, MD, of Harvard Medical School and Massachusetts General Hospital, Boston, said in an interview. “The ability to explore these options as monotherapy and in novel combinations has dramatically expanded our treatment options.”
Much depends on the underlying genetic profile of the disease, he said. “There certainly have been gains in patient survival in AML, but those improvements remain fairly heterogeneous and dependent on the underlying genetic profile of the disease. For instance, advances in FLT3- and IDH1/2-mutated AML are a direct result of the improvements in targeted therapies directed at these mutations. Similarly, some molecular and cytogenetic subtypes of AML are particularly responsive to venetoclax-based regimens, and these regimens have been expanded to previously undertreated populations, particularly those over age 60.”
Specifically, Dr. LeBlanc said, the Food and Drug Administration has approved “3 different FLT3 inhibitors, 2 IDH1 inhibitors, 1 IDH2 inhibitor, a BCL-2 inhibitor, a smoothened/hedgehog pathway inhibitor, an oral maintenance chemotherapy/hypomethylating agent (CC-486/oral azacitidine), a CD33-targeting antibody-drug conjugate, and even a novel formulation of two older chemotherapies that improves efficacy in a poor prognosis subgroup (CPX-351/liposomal daunorubicin and cytarabine).”
There’s also been a shift in treatment protocols for patients who were not fit for intensive chemotherapy. In the past, he said, it was standard “to give single-agent hypomethylating chemotherapy with azacitidine or decitabine, or in some contexts, low-dose chemotherapy with cytarabine. Today, many patients who are older and/or more frail are receiving novel therapies either alone or in combination, with greater efficacy and longer duration of response than previously seen with chemotherapy alone.”
Outcomes Improve but Remain Grim in High-Risk Cases
As a result, Dr. LeBlanc said, “we’re definitely seeing much better outcomes in AML overall. It takes some time to prove this via outcomes data assessments in a large population, but I expect that registries will show significant improvements in overall survival in the coming years, owing to the many new FDA approvals in AML”
Dr. LeBlanc highlighted national data from 2013-2019 showing that the 5-year relative survival rate from AML is 31.7%. That’s up from 26% just a few years ago, and the numbers “always lag several years behind the current year of practice,” he said. However, “the major area where we still have relatively poor outcomes and significant unmet needs remains the ‘adverse risk’ group of patients, particularly those who are older and/or not candidates for hematopoietic stem cell transplantation, which generally is the only potentially curative option for adverse-risk AML.”
He went on to say that “this risk grouping includes those with TP53 mutations, most of which confer a particularly poor prognosis. Exciting therapies that many of us were hoping would prove effective in this subgroup have unfortunately failed in recent clinical trials. We still have a lot of work to do in adverse-risk AML particularly, and also for those whose leukemia has relapsed.”
Mikkael Sekeres, MD, MS, chief of the Division of Hematology at the University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, agreed that more progress is needed, since survival rates are low even as lifespans improve. One key will be “better identifying subtypes of acute myeloid leukemia, and identifying the therapies that will benefit those people most,” he said in an interview. On the other side, it’s important to identify “when aggressive therapies aren’t going to work in somebody and maybe turn toward less-aggressive approaches so we can maximize that person’s quality of life.”
What advice do AML experts have for their colleagues? Dr. LeBlanc said “older patients are not often enough considered for allogeneic stem cell transplantation, which could potentially cure their AML when given as a consolidation treatment for those in remission. I have several patients who are healthy and in their 70s who have enormously benefited from transplants and are now being several years out from transplant with adverse risk AML and without relapse. They’ve had no significant impairments of their quality of life, including no significant graft vs. host disease.”
Dr. Sekeres highlighted the American Society of Hematology’s guidelines for treating older adults with AML, which are currently being updated. It’s crucial to order genetic testing “up front,” he said. “I’m often pleasantly surprised when genetic testing returns and reveals that I have other treatment options.”
However, it’s crucial to understand a patient’s priorities. “I’ve had patients who are 75 who say to me, ‘Do everything under the sun to get rid of my leukemia, I want to live as long as possible.’ And I’ve had patients who say, ‘I want to see as little of doctors and nurses as I can. I want you to maximize my quality of life and keep me out of the hospital.’ ”
Dr. Sekeres also noted that insurers may not cover some pill-based AML treatments such as venetoclax. “We work with our patients and assistance programs. For the most part, we’re pretty successful at getting these drugs for our patients,” he said.
In Pediatrics, Clinical Trials Are Crucial
AML in children is less well-known than in adults, since the number of cases is so small. The disease is diagnosed in about 500 children a year in the United States, according to St. Jude Children’s Research Hospital, adding, however, that AML is “the most common second cancer among children treated for other cancers.”
AML in children gained attention earlier this year when the 2-year-old daughter of a Boston Herald NFL reporter died of the disease following a bone marrow transplant and chemotherapy. Despite the agonies of her treatment, reporter Doug Kyed told a reporter that his daughter Hallie “was still able to find joy every day.”
In an interview, hematologist/oncologist Sarah K. Tasian, MD, of Children’s Hospital of Philadelphia, said researchers are discovering that pediatric AML is significantly different on from a biological perspective from adult AML. “We’ve come to understand a lot more about who these patients are, what makes these leukemias tick, and what their Achilles’ heels are. Then we can align that with the clinical trials outcome data that we have.”
About 80%-90% of pediatric patients with AML nationwide are enrolled in clinical trials, Dr. Tasian said, and an international consortium called the Children’s Oncology Group gathers data about genetics. About 60%-70% of patients will be cured, she added.
However, “we’ve kind of been stuck for about the last 20 years,” she said. “A lot of improving the survival of patients has not been because we’ve been better at chemotherapy or using new chemo, but because we’ve gotten better at supportive care, at treating infections that can be fatal.”
There haven’t been major conflicts with insurers over coverage, she said, although drug shortages are a problem, especially in relapsed AML.
As for advice to colleagues, Dr. Tasian counseled them to understand the importance of genetic testing and the expanding role of stem cell transplants. “We are now transplanting somewhere between 30% and 50% of children with AML, which is a higher rate than we used to do,” she said. The number is up thanks to genetic testing that reveals which patients are most likely to benefit.
Also, she noted, “the chemotherapy that we get to these patients is really strong, and patients have a lot of complications. Really pay attention to supportive care.”
Dr. LeBlanc reported ties with AbbVie, Agios/Servier, Astellas, BMS/Celgene, Genentech, Pfizer, Incyte, Rige, Deverra, GSK, Jazz, and Seattle Genetics. Dr. Sekeres discloses relationships with BMS and Kurome. Dr. Tasian serves as the Leukemia & Lymphoma Society Pediatric Acute Leukemia consortium clinical trials leader and works with pharmaceutical companies on clinical trials under confidentiality agreements. Dr. Brunner has no disclosures.
Are Food Emulsifiers Associated With Increased Cancer Risk?
Food emulsifiers are among the most widespread food additives.
Ultraprocessed foods constitute a significant part of our diet, representing approximately 30% of energy intake in France.
Large epidemiologic studies have already linked diets rich in ultraprocessed products to an increased risk for cardiovascular diseases, diabetes, obesity, and mortality. Possible explanations for this association include the presence of additives, particularly emulsifiers. These additives are intended to improve the texture and shelf life of foods.
Recent experimental studies have shown that emulsifiers alter the gut microbiota and may lead to low-grade inflammation. Dysbiosis and chronic inflammation not only increase the risk for inflammatory bowel diseases but are also implicated in the etiology of several other chronic pathologies and certain extraintestinal cancers.
The NutriNet-Santé study provided extensive information on the dietary habits of > 100,000 French participants. A new analysis was conducted, examining the possible link between the presence of emulsifiers in the diet and cancer occurrence. Data from 92,000 participants (78.8% women) were utilized. They covered an average follow-up of 6.7 years, during which 2604 cancer cases were diagnosed, including 750 breast cancers, 322 prostate cancers, and 207 colorectal cancers.
In this cohort, the risk for cancer increased with a higher presence in the diet of products containing certain emulsifiers widely used in industrial food in Europe: Carrageenans (E407), mono- and diglycerides of fatty acids (E471), pectins (E440), and sodium carbonate (E500).
Notably, the highest consumption of mono- and diglycerides of fatty acids (E471) was associated with a 15% increase in the risk for all types of cancer, a 24% increase in breast cancer risk, and a 46% increase in prostate cancer risk. The highest consumption of carrageenans (E407) was associated with a 28% increase in breast cancer risk.
In an analysis by menopausal status, the risk for breast cancer before menopause was associated with high consumption of diphosphates (E450; 45% increase), pectins (E440; 55% increase), and sodium bicarbonate (E500; 48% increase). No link was found between emulsifier consumption and colorectal cancer risk. While some associations were observed for other emulsifiers, they did not persist in sensitivity analyses.
The European Food Safety Agency recently evaluated the risks of emulsifiers, however, and found no safety issues or need to limit daily consumption of several of them, notably E471.
It is certain that cancer is multifactorial, and a single factor (here, exposure to emulsifiers) will not significantly increase the risk. However, while not essential to human health, emulsifiers are widely prevalent in the global market. Therefore, if causality is established, the increased risk could translate into a significant number of preventable cancers at the population level. Confirmation of this causal link will need to be obtained through experimental and epidemiological studies.
This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Food emulsifiers are among the most widespread food additives.
Ultraprocessed foods constitute a significant part of our diet, representing approximately 30% of energy intake in France.
Large epidemiologic studies have already linked diets rich in ultraprocessed products to an increased risk for cardiovascular diseases, diabetes, obesity, and mortality. Possible explanations for this association include the presence of additives, particularly emulsifiers. These additives are intended to improve the texture and shelf life of foods.
Recent experimental studies have shown that emulsifiers alter the gut microbiota and may lead to low-grade inflammation. Dysbiosis and chronic inflammation not only increase the risk for inflammatory bowel diseases but are also implicated in the etiology of several other chronic pathologies and certain extraintestinal cancers.
The NutriNet-Santé study provided extensive information on the dietary habits of > 100,000 French participants. A new analysis was conducted, examining the possible link between the presence of emulsifiers in the diet and cancer occurrence. Data from 92,000 participants (78.8% women) were utilized. They covered an average follow-up of 6.7 years, during which 2604 cancer cases were diagnosed, including 750 breast cancers, 322 prostate cancers, and 207 colorectal cancers.
In this cohort, the risk for cancer increased with a higher presence in the diet of products containing certain emulsifiers widely used in industrial food in Europe: Carrageenans (E407), mono- and diglycerides of fatty acids (E471), pectins (E440), and sodium carbonate (E500).
Notably, the highest consumption of mono- and diglycerides of fatty acids (E471) was associated with a 15% increase in the risk for all types of cancer, a 24% increase in breast cancer risk, and a 46% increase in prostate cancer risk. The highest consumption of carrageenans (E407) was associated with a 28% increase in breast cancer risk.
In an analysis by menopausal status, the risk for breast cancer before menopause was associated with high consumption of diphosphates (E450; 45% increase), pectins (E440; 55% increase), and sodium bicarbonate (E500; 48% increase). No link was found between emulsifier consumption and colorectal cancer risk. While some associations were observed for other emulsifiers, they did not persist in sensitivity analyses.
The European Food Safety Agency recently evaluated the risks of emulsifiers, however, and found no safety issues or need to limit daily consumption of several of them, notably E471.
It is certain that cancer is multifactorial, and a single factor (here, exposure to emulsifiers) will not significantly increase the risk. However, while not essential to human health, emulsifiers are widely prevalent in the global market. Therefore, if causality is established, the increased risk could translate into a significant number of preventable cancers at the population level. Confirmation of this causal link will need to be obtained through experimental and epidemiological studies.
This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Food emulsifiers are among the most widespread food additives.
Ultraprocessed foods constitute a significant part of our diet, representing approximately 30% of energy intake in France.
Large epidemiologic studies have already linked diets rich in ultraprocessed products to an increased risk for cardiovascular diseases, diabetes, obesity, and mortality. Possible explanations for this association include the presence of additives, particularly emulsifiers. These additives are intended to improve the texture and shelf life of foods.
Recent experimental studies have shown that emulsifiers alter the gut microbiota and may lead to low-grade inflammation. Dysbiosis and chronic inflammation not only increase the risk for inflammatory bowel diseases but are also implicated in the etiology of several other chronic pathologies and certain extraintestinal cancers.
The NutriNet-Santé study provided extensive information on the dietary habits of > 100,000 French participants. A new analysis was conducted, examining the possible link between the presence of emulsifiers in the diet and cancer occurrence. Data from 92,000 participants (78.8% women) were utilized. They covered an average follow-up of 6.7 years, during which 2604 cancer cases were diagnosed, including 750 breast cancers, 322 prostate cancers, and 207 colorectal cancers.
In this cohort, the risk for cancer increased with a higher presence in the diet of products containing certain emulsifiers widely used in industrial food in Europe: Carrageenans (E407), mono- and diglycerides of fatty acids (E471), pectins (E440), and sodium carbonate (E500).
Notably, the highest consumption of mono- and diglycerides of fatty acids (E471) was associated with a 15% increase in the risk for all types of cancer, a 24% increase in breast cancer risk, and a 46% increase in prostate cancer risk. The highest consumption of carrageenans (E407) was associated with a 28% increase in breast cancer risk.
In an analysis by menopausal status, the risk for breast cancer before menopause was associated with high consumption of diphosphates (E450; 45% increase), pectins (E440; 55% increase), and sodium bicarbonate (E500; 48% increase). No link was found between emulsifier consumption and colorectal cancer risk. While some associations were observed for other emulsifiers, they did not persist in sensitivity analyses.
The European Food Safety Agency recently evaluated the risks of emulsifiers, however, and found no safety issues or need to limit daily consumption of several of them, notably E471.
It is certain that cancer is multifactorial, and a single factor (here, exposure to emulsifiers) will not significantly increase the risk. However, while not essential to human health, emulsifiers are widely prevalent in the global market. Therefore, if causality is established, the increased risk could translate into a significant number of preventable cancers at the population level. Confirmation of this causal link will need to be obtained through experimental and epidemiological studies.
This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Democratic Lawmakers Press Pfizer on Chemotherapy Drug Shortages
In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.
A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”
What is the basis for concern?
All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.
What has the government done in response to the recent shortages?
The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.
What can the lawmakers expect to achieve with their letter?
By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”
Why did the committee target Pfizer specifically?
Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”
The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.
What is being demanded of Pfizer?
Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.
In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.
A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”
What is the basis for concern?
All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.
What has the government done in response to the recent shortages?
The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.
What can the lawmakers expect to achieve with their letter?
By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”
Why did the committee target Pfizer specifically?
Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”
The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.
What is being demanded of Pfizer?
Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.
In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.
A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”
What is the basis for concern?
All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.
What has the government done in response to the recent shortages?
The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.
What can the lawmakers expect to achieve with their letter?
By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”
Why did the committee target Pfizer specifically?
Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”
The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.
What is being demanded of Pfizer?
Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.