Conference Coverage

BOSTON – The neurologic symptoms of long COVID appear to be explained by a phenomenon known as antigenic imprinting, which involves a misdirected immune response to the SARS-CoV2 virus, according to a collaborative study presented at the 2023 annual meeting of the American Academy of Neurology.

Already documented in several other viral infections, such as influenza and human immunodeficiency virus, antigenic imprinting results in production of antibodies to previously encountered viral infections rather than to the immediate threat, according to Marianna Spatola, MD, PhD, a research fellow at the Ragon Institute, Harvard University, Cambridge, Mass.
 

Original antigenic sin

In the case of persistent neurologic symptoms after COVID, a condition known as neuroPASC (neurological postacute sequelae of SARS-CoV2 infection), antibodies produced for previously encountered coronaviruses rather than for SARS-CoV2 might explain most or all cases, according to the data Dr. Spatola presented.

The evidence for this explanation was drawn from a study of 112 patients evaluated months after an acute episode of COVID-19. Of these, 18 patients had persistent neurologic dysfunction. When compared with the 94 whose infection resolved without sequelae, the patients with prolonged neurologic impairments had relatively low systemic antibody response to SARS-CoV2. However, they showed relatively high antibody responses against other coronaviruses.

This is a pattern consistent with antigenic imprinting, a concept first described more than 60 years ago as original antigenic sin. When the immune system becomes imprinted with an antigen from the first encountered virus from a family of pathogens, it governs all subsequent antibody responses, according to several published studies that have described and evaluated this concept.
 

Additional evidence

In Dr. Spatola’s study, other differences, particularly in regard to the cerebrospinal fluid (CSF), further supported the role of antigenic imprinting as a cause of neuroPASC. For one, those with elevated immune responses to other common coronaviruses rather than SARS-CoV2 in the CSF relative to the periphery were more likely to have a bad outcome in regard to neurologic symptoms.

Moreover, the CSF in neuroPASC patients “was characterized by increased IgG1 and absence of IgM, suggesting compartmentalized humoral responses within the CSF through selective transfer of antibodies from the serum to the CSF across the blood-brain barrier rather than through intrathecal synthesis,” Dr. Spatola reported.

In the case of COVID-19, the propensity for antigenic imprinting is not difficult to understand.

“The common cold coronaviruses are pretty similar to SARS-CoV2, but they are not exactly the same,” Dr. Spatola said. Her work and studies by others suggest that when antigenic imprinting occurs, “it prevents full maturation of the antibody response.”

NeuroPASC is one of many manifestations of long COVID, but Dr. Spatola pointed out that the immune response in the CSF is unique and the causes of prolonged neurologic impairment after COVID-19 are likely to involve different mechanisms than other long-COVID symptoms.

“Antibodies in the brain are functionally different,” said Dr. Spatola, noting for example that antibody-directed defenses against viral threats show a greater relative reliance on phagocytosis. This might become important in the development of therapeutics for neurologic symptoms of long COVID.
 

A different phenomenon

The manifestations of neuroPASC are heterogeneous and can include confusion, cognitive dysfunction, headache, encephalitis, and other impairments. Neurologic symptoms occur during acute SARS-CoV2 infections, but neuroPASC appears to be a different phenomenon. These symptoms, which develop after the initial respiratory disease has resolved, were attributed by Dr. Spatola to persistent inflammation that is not necessarily directly related to ongoing infection.

“The reason why some patients develop neuroPASC is unknown, but I think the evidence has pointed to a role for the immune system rather than the virus itself,” Dr. Spatola said.

Currently, neuroPASC is a clinical diagnosis but Dr. Spatola and her coinvestigators are conducting research to identify biomarkers. A viable diagnostic test is not expected imminently. They have identified 150 different features with potential relevance to neuroPASC.

In their comparison of those who did relative to those who did not develop neuroPASC, the initial studies were undertaken 2-4 months after the acute COVID-19 symptoms had resolved. The patients with neuroPASC and those without neurologic sequelae have now been followed for 6-8 months, which Dr. Spatola said was too short to draw firm conclusions about outcomes.
 

An evolving concept

Despite the small sample size of this study, these are “very interesting data” for considering the pathogenesis of neuroPASC, which is “a concept that is still evolving,” according to Natalia S. Rost, MD, chief of the stroke division, department of neurology, Massachusetts General Hospital, Boston.

Applied to SARS-CoV2, the concept of original antigenic sin “is new” but Dr. Rost said that it might help differentiate neuroPASC from acute neurologic symptoms of COVID-19, which include stroke. She indicated that the work performed by Dr. Spatola and others might eventually explain the pathology while leading to treatment strategies. She cautioned that the concepts explored in this study “need to be further developed” through larger sample sizes and the exploration of other variables that support the hypothesis.

Dr. Spatola and Dr. Rost report no potential conflicts of interest.

BOSTON – The neurologic symptoms of long COVID appear to be explained by a phenomenon known as antigenic imprinting, which involves a misdirected immune response to the SARS-CoV2 virus, according to a collaborative study presented at the 2023 annual meeting of the American Academy of Neurology.

Already documented in several other viral infections, such as influenza and human immunodeficiency virus, antigenic imprinting results in production of antibodies to previously encountered viral infections rather than to the immediate threat, according to Marianna Spatola, MD, PhD, a research fellow at the Ragon Institute, Harvard University, Cambridge, Mass.
 

Original antigenic sin

In the case of persistent neurologic symptoms after COVID, a condition known as neuroPASC (neurological postacute sequelae of SARS-CoV2 infection), antibodies produced for previously encountered coronaviruses rather than for SARS-CoV2 might explain most or all cases, according to the data Dr. Spatola presented.

The evidence for this explanation was drawn from a study of 112 patients evaluated months after an acute episode of COVID-19. Of these, 18 patients had persistent neurologic dysfunction. When compared with the 94 whose infection resolved without sequelae, the patients with prolonged neurologic impairments had relatively low systemic antibody response to SARS-CoV2. However, they showed relatively high antibody responses against other coronaviruses.

This is a pattern consistent with antigenic imprinting, a concept first described more than 60 years ago as original antigenic sin. When the immune system becomes imprinted with an antigen from the first encountered virus from a family of pathogens, it governs all subsequent antibody responses, according to several published studies that have described and evaluated this concept.
 

Additional evidence

In Dr. Spatola’s study, other differences, particularly in regard to the cerebrospinal fluid (CSF), further supported the role of antigenic imprinting as a cause of neuroPASC. For one, those with elevated immune responses to other common coronaviruses rather than SARS-CoV2 in the CSF relative to the periphery were more likely to have a bad outcome in regard to neurologic symptoms.

Moreover, the CSF in neuroPASC patients “was characterized by increased IgG1 and absence of IgM, suggesting compartmentalized humoral responses within the CSF through selective transfer of antibodies from the serum to the CSF across the blood-brain barrier rather than through intrathecal synthesis,” Dr. Spatola reported.

In the case of COVID-19, the propensity for antigenic imprinting is not difficult to understand.

“The common cold coronaviruses are pretty similar to SARS-CoV2, but they are not exactly the same,” Dr. Spatola said. Her work and studies by others suggest that when antigenic imprinting occurs, “it prevents full maturation of the antibody response.”

NeuroPASC is one of many manifestations of long COVID, but Dr. Spatola pointed out that the immune response in the CSF is unique and the causes of prolonged neurologic impairment after COVID-19 are likely to involve different mechanisms than other long-COVID symptoms.

“Antibodies in the brain are functionally different,” said Dr. Spatola, noting for example that antibody-directed defenses against viral threats show a greater relative reliance on phagocytosis. This might become important in the development of therapeutics for neurologic symptoms of long COVID.
 

A different phenomenon

The manifestations of neuroPASC are heterogeneous and can include confusion, cognitive dysfunction, headache, encephalitis, and other impairments. Neurologic symptoms occur during acute SARS-CoV2 infections, but neuroPASC appears to be a different phenomenon. These symptoms, which develop after the initial respiratory disease has resolved, were attributed by Dr. Spatola to persistent inflammation that is not necessarily directly related to ongoing infection.

“The reason why some patients develop neuroPASC is unknown, but I think the evidence has pointed to a role for the immune system rather than the virus itself,” Dr. Spatola said.

Currently, neuroPASC is a clinical diagnosis but Dr. Spatola and her coinvestigators are conducting research to identify biomarkers. A viable diagnostic test is not expected imminently. They have identified 150 different features with potential relevance to neuroPASC.

In their comparison of those who did relative to those who did not develop neuroPASC, the initial studies were undertaken 2-4 months after the acute COVID-19 symptoms had resolved. The patients with neuroPASC and those without neurologic sequelae have now been followed for 6-8 months, which Dr. Spatola said was too short to draw firm conclusions about outcomes.
 

An evolving concept

Despite the small sample size of this study, these are “very interesting data” for considering the pathogenesis of neuroPASC, which is “a concept that is still evolving,” according to Natalia S. Rost, MD, chief of the stroke division, department of neurology, Massachusetts General Hospital, Boston.

Applied to SARS-CoV2, the concept of original antigenic sin “is new” but Dr. Rost said that it might help differentiate neuroPASC from acute neurologic symptoms of COVID-19, which include stroke. She indicated that the work performed by Dr. Spatola and others might eventually explain the pathology while leading to treatment strategies. She cautioned that the concepts explored in this study “need to be further developed” through larger sample sizes and the exploration of other variables that support the hypothesis.

Dr. Spatola and Dr. Rost report no potential conflicts of interest.

BOSTON – The neurologic symptoms of long COVID appear to be explained by a phenomenon known as antigenic imprinting, which involves a misdirected immune response to the SARS-CoV2 virus, according to a collaborative study presented at the 2023 annual meeting of the American Academy of Neurology.

Already documented in several other viral infections, such as influenza and human immunodeficiency virus, antigenic imprinting results in production of antibodies to previously encountered viral infections rather than to the immediate threat, according to Marianna Spatola, MD, PhD, a research fellow at the Ragon Institute, Harvard University, Cambridge, Mass.
 

Original antigenic sin

In the case of persistent neurologic symptoms after COVID, a condition known as neuroPASC (neurological postacute sequelae of SARS-CoV2 infection), antibodies produced for previously encountered coronaviruses rather than for SARS-CoV2 might explain most or all cases, according to the data Dr. Spatola presented.

The evidence for this explanation was drawn from a study of 112 patients evaluated months after an acute episode of COVID-19. Of these, 18 patients had persistent neurologic dysfunction. When compared with the 94 whose infection resolved without sequelae, the patients with prolonged neurologic impairments had relatively low systemic antibody response to SARS-CoV2. However, they showed relatively high antibody responses against other coronaviruses.

This is a pattern consistent with antigenic imprinting, a concept first described more than 60 years ago as original antigenic sin. When the immune system becomes imprinted with an antigen from the first encountered virus from a family of pathogens, it governs all subsequent antibody responses, according to several published studies that have described and evaluated this concept.
 

Additional evidence

In Dr. Spatola’s study, other differences, particularly in regard to the cerebrospinal fluid (CSF), further supported the role of antigenic imprinting as a cause of neuroPASC. For one, those with elevated immune responses to other common coronaviruses rather than SARS-CoV2 in the CSF relative to the periphery were more likely to have a bad outcome in regard to neurologic symptoms.

Moreover, the CSF in neuroPASC patients “was characterized by increased IgG1 and absence of IgM, suggesting compartmentalized humoral responses within the CSF through selective transfer of antibodies from the serum to the CSF across the blood-brain barrier rather than through intrathecal synthesis,” Dr. Spatola reported.

In the case of COVID-19, the propensity for antigenic imprinting is not difficult to understand.

“The common cold coronaviruses are pretty similar to SARS-CoV2, but they are not exactly the same,” Dr. Spatola said. Her work and studies by others suggest that when antigenic imprinting occurs, “it prevents full maturation of the antibody response.”

NeuroPASC is one of many manifestations of long COVID, but Dr. Spatola pointed out that the immune response in the CSF is unique and the causes of prolonged neurologic impairment after COVID-19 are likely to involve different mechanisms than other long-COVID symptoms.

“Antibodies in the brain are functionally different,” said Dr. Spatola, noting for example that antibody-directed defenses against viral threats show a greater relative reliance on phagocytosis. This might become important in the development of therapeutics for neurologic symptoms of long COVID.
 

A different phenomenon

The manifestations of neuroPASC are heterogeneous and can include confusion, cognitive dysfunction, headache, encephalitis, and other impairments. Neurologic symptoms occur during acute SARS-CoV2 infections, but neuroPASC appears to be a different phenomenon. These symptoms, which develop after the initial respiratory disease has resolved, were attributed by Dr. Spatola to persistent inflammation that is not necessarily directly related to ongoing infection.

“The reason why some patients develop neuroPASC is unknown, but I think the evidence has pointed to a role for the immune system rather than the virus itself,” Dr. Spatola said.

Currently, neuroPASC is a clinical diagnosis but Dr. Spatola and her coinvestigators are conducting research to identify biomarkers. A viable diagnostic test is not expected imminently. They have identified 150 different features with potential relevance to neuroPASC.

In their comparison of those who did relative to those who did not develop neuroPASC, the initial studies were undertaken 2-4 months after the acute COVID-19 symptoms had resolved. The patients with neuroPASC and those without neurologic sequelae have now been followed for 6-8 months, which Dr. Spatola said was too short to draw firm conclusions about outcomes.
 

An evolving concept

Despite the small sample size of this study, these are “very interesting data” for considering the pathogenesis of neuroPASC, which is “a concept that is still evolving,” according to Natalia S. Rost, MD, chief of the stroke division, department of neurology, Massachusetts General Hospital, Boston.

Applied to SARS-CoV2, the concept of original antigenic sin “is new” but Dr. Rost said that it might help differentiate neuroPASC from acute neurologic symptoms of COVID-19, which include stroke. She indicated that the work performed by Dr. Spatola and others might eventually explain the pathology while leading to treatment strategies. She cautioned that the concepts explored in this study “need to be further developed” through larger sample sizes and the exploration of other variables that support the hypothesis.

Dr. Spatola and Dr. Rost report no potential conflicts of interest.

PHOENIX – Of the federal and state malpractice lawsuits filed against dermatologists between 2011 and 2022, half were related to accidental injury, followed by incorrect or delayed diagnoses, and the defendants were more likely to be male.

Those are among key findings from a study that aimed to determine the reasons patients pursue litigation against dermatologists.

“The number of lawsuits against physicians continues to climb annually,” Young Lim, MD, PhD, said at the annual conference of the American Society for Laser Medicine and Surgery, where the results were presented during an abstract session. “Depending on the study, anywhere between 75 to 99 percent of physicians will face a lawsuit by age 65. A clear understanding of prior litigations will help mitigate similar errors in future practice and promote safer, higher quality care.”

Dr. Lim, a dermatology resident at Massachusetts General Hospital and Harvard Medical School, Boston, along with Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at MGH, and H. Ray Jalian, MD, a cosmetic dermatologist who practices in Los Angeles, used two large national database repositories, WestlawNext and LexisNexis, to retrospectively analyze legal documents following a query using “dermatology” and “dermatologist” as search terms to capture all variety of litigations. They excluded cases in which litigation did not involve patient care as well as those in which the dermatologist was the plaintiff and those in which the dermatologist was involved as a third party.

The final analysis consisted of 54 claims, comprising 43 state and 11 federal cases. Of the 54 cases, 35 involved a male defendant, 12 involved a female defendant, and 7 cases either did not specify the gender of the defendant or involved multiple defendants. Of the 35 cases involving a male defendant, 23 (66%) were brought by female plaintiffs.

Most cases (49, or 91%) involved a defendant dermatologist in private practice while the remaining 5 involved a defendant dermatologist in an academic setting.

The most common reason for litigation was accidental injury (27 cases, or 50%), followed by incorrect or delayed diagnoses (22 cases, or 41%). Five cases resulted from the dermatologist failing to communicate important information, such as postop care instructions or obtaining informed consent.

Of all 54 cases 30 (56%) were dismissed prior to trial, while 24 (44%) resulted in a judgment for the plaintiff. According to Dr. Lim, payout information was available for only five cases, and ranged from $15,000 (injury from laser) to $1,950,000 (delayed diagnosis of malignant melanoma).

“While lawsuits from patients against dermatologists largely involve injury from elective procedures, clinicians should practice caution regarding missed or delayed diagnoses when practicing medical dermatology,” the authors concluded in their abstract. “Ensuring that critical information is shared with patients and obtaining proper written consent will also safeguard against easily-avoidable litigations.”

Christopher B. Zachary, MBBS, professor and chair emeritus of the department of dermatology at the University of California, Irvine, who was asked to comment on the study, said that the findings are a reminder that lack of attention to the most simply performed aspects of care can be the reasons patients will seek medical malpractice redress.

“Consent requires careful and thoughtful explanation of a planned procedure, which should then be recorded in the chart to avoid future confusion,” Dr. Zachary told this news organization. “A patient’s signature on a consent form obtained by a staff member is clearly inadequate if not accompanied by a clear and understandable preoperative discussion. Words, images, video are all elements that aid patients’ comprehension of a planned procedure. And postoperative instructions given to the patients while on the laser table are commonly forgotten by the patient and must be accompanied by written advice summary. Patients will frequently misremember instructions and can be overwhelmed by medical jargon.”

Neither the researchers nor Dr. Zachary reported having relevant financial disclosures.

PHOENIX – Of the federal and state malpractice lawsuits filed against dermatologists between 2011 and 2022, half were related to accidental injury, followed by incorrect or delayed diagnoses, and the defendants were more likely to be male.

Those are among key findings from a study that aimed to determine the reasons patients pursue litigation against dermatologists.

“The number of lawsuits against physicians continues to climb annually,” Young Lim, MD, PhD, said at the annual conference of the American Society for Laser Medicine and Surgery, where the results were presented during an abstract session. “Depending on the study, anywhere between 75 to 99 percent of physicians will face a lawsuit by age 65. A clear understanding of prior litigations will help mitigate similar errors in future practice and promote safer, higher quality care.”

Dr. Lim, a dermatology resident at Massachusetts General Hospital and Harvard Medical School, Boston, along with Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at MGH, and H. Ray Jalian, MD, a cosmetic dermatologist who practices in Los Angeles, used two large national database repositories, WestlawNext and LexisNexis, to retrospectively analyze legal documents following a query using “dermatology” and “dermatologist” as search terms to capture all variety of litigations. They excluded cases in which litigation did not involve patient care as well as those in which the dermatologist was the plaintiff and those in which the dermatologist was involved as a third party.

The final analysis consisted of 54 claims, comprising 43 state and 11 federal cases. Of the 54 cases, 35 involved a male defendant, 12 involved a female defendant, and 7 cases either did not specify the gender of the defendant or involved multiple defendants. Of the 35 cases involving a male defendant, 23 (66%) were brought by female plaintiffs.

Most cases (49, or 91%) involved a defendant dermatologist in private practice while the remaining 5 involved a defendant dermatologist in an academic setting.

The most common reason for litigation was accidental injury (27 cases, or 50%), followed by incorrect or delayed diagnoses (22 cases, or 41%). Five cases resulted from the dermatologist failing to communicate important information, such as postop care instructions or obtaining informed consent.

Of all 54 cases 30 (56%) were dismissed prior to trial, while 24 (44%) resulted in a judgment for the plaintiff. According to Dr. Lim, payout information was available for only five cases, and ranged from $15,000 (injury from laser) to $1,950,000 (delayed diagnosis of malignant melanoma).

“While lawsuits from patients against dermatologists largely involve injury from elective procedures, clinicians should practice caution regarding missed or delayed diagnoses when practicing medical dermatology,” the authors concluded in their abstract. “Ensuring that critical information is shared with patients and obtaining proper written consent will also safeguard against easily-avoidable litigations.”

Christopher B. Zachary, MBBS, professor and chair emeritus of the department of dermatology at the University of California, Irvine, who was asked to comment on the study, said that the findings are a reminder that lack of attention to the most simply performed aspects of care can be the reasons patients will seek medical malpractice redress.

“Consent requires careful and thoughtful explanation of a planned procedure, which should then be recorded in the chart to avoid future confusion,” Dr. Zachary told this news organization. “A patient’s signature on a consent form obtained by a staff member is clearly inadequate if not accompanied by a clear and understandable preoperative discussion. Words, images, video are all elements that aid patients’ comprehension of a planned procedure. And postoperative instructions given to the patients while on the laser table are commonly forgotten by the patient and must be accompanied by written advice summary. Patients will frequently misremember instructions and can be overwhelmed by medical jargon.”

Neither the researchers nor Dr. Zachary reported having relevant financial disclosures.

PHOENIX – Of the federal and state malpractice lawsuits filed against dermatologists between 2011 and 2022, half were related to accidental injury, followed by incorrect or delayed diagnoses, and the defendants were more likely to be male.

Those are among key findings from a study that aimed to determine the reasons patients pursue litigation against dermatologists.

“The number of lawsuits against physicians continues to climb annually,” Young Lim, MD, PhD, said at the annual conference of the American Society for Laser Medicine and Surgery, where the results were presented during an abstract session. “Depending on the study, anywhere between 75 to 99 percent of physicians will face a lawsuit by age 65. A clear understanding of prior litigations will help mitigate similar errors in future practice and promote safer, higher quality care.”

Dr. Lim, a dermatology resident at Massachusetts General Hospital and Harvard Medical School, Boston, along with Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at MGH, and H. Ray Jalian, MD, a cosmetic dermatologist who practices in Los Angeles, used two large national database repositories, WestlawNext and LexisNexis, to retrospectively analyze legal documents following a query using “dermatology” and “dermatologist” as search terms to capture all variety of litigations. They excluded cases in which litigation did not involve patient care as well as those in which the dermatologist was the plaintiff and those in which the dermatologist was involved as a third party.

The final analysis consisted of 54 claims, comprising 43 state and 11 federal cases. Of the 54 cases, 35 involved a male defendant, 12 involved a female defendant, and 7 cases either did not specify the gender of the defendant or involved multiple defendants. Of the 35 cases involving a male defendant, 23 (66%) were brought by female plaintiffs.

Most cases (49, or 91%) involved a defendant dermatologist in private practice while the remaining 5 involved a defendant dermatologist in an academic setting.

The most common reason for litigation was accidental injury (27 cases, or 50%), followed by incorrect or delayed diagnoses (22 cases, or 41%). Five cases resulted from the dermatologist failing to communicate important information, such as postop care instructions or obtaining informed consent.

Of all 54 cases 30 (56%) were dismissed prior to trial, while 24 (44%) resulted in a judgment for the plaintiff. According to Dr. Lim, payout information was available for only five cases, and ranged from $15,000 (injury from laser) to $1,950,000 (delayed diagnosis of malignant melanoma).

“While lawsuits from patients against dermatologists largely involve injury from elective procedures, clinicians should practice caution regarding missed or delayed diagnoses when practicing medical dermatology,” the authors concluded in their abstract. “Ensuring that critical information is shared with patients and obtaining proper written consent will also safeguard against easily-avoidable litigations.”

Christopher B. Zachary, MBBS, professor and chair emeritus of the department of dermatology at the University of California, Irvine, who was asked to comment on the study, said that the findings are a reminder that lack of attention to the most simply performed aspects of care can be the reasons patients will seek medical malpractice redress.

“Consent requires careful and thoughtful explanation of a planned procedure, which should then be recorded in the chart to avoid future confusion,” Dr. Zachary told this news organization. “A patient’s signature on a consent form obtained by a staff member is clearly inadequate if not accompanied by a clear and understandable preoperative discussion. Words, images, video are all elements that aid patients’ comprehension of a planned procedure. And postoperative instructions given to the patients while on the laser table are commonly forgotten by the patient and must be accompanied by written advice summary. Patients will frequently misremember instructions and can be overwhelmed by medical jargon.”

Neither the researchers nor Dr. Zachary reported having relevant financial disclosures.

Regular meditation reduced depression by roughly 44% in adults with coronary artery disease who were involved in a cardiovascular rehabilitation program.

An increasing body of research supports the impact of psychological risk factors including stress, personality type, anger, and hostility on conditions such as depression and anxiety, but also social isolation and low socioeconomic status, Ana Luisa Vitorino Monteiro, MD, of the University of Lisbon said in a presentation at the annual congress of the European Association of Preventive Cardiology. In addition, “stress, anxiety, and depression deteriorate the cardiovascular (CV) system through psycho-neuro-immunoendocrinology system and behavioral pathways.”

Meditation as a tool for stress management has been gaining popularity, but its use as part of a CV rehabilitation program as a complementary therapy has not been well studied, she added.

Dr. Monteiro and colleagues recruited 80 adults with CAD who were undergoing CV rehabilitation to join a meditation program. Of these, 48 accepted (60%) and 40% declined. Those who accepted were part of an exercise-based CV rehabilitation program that met three times a week for at least 6 months. The mean age of the participants was 65 years, and 80% were male.

Participants were randomized to an intervention group with a weekly 90-minute session that included breathing and meditation for 1 month in addition to usual care, or to usual care in the rehabilitation program. Over the next 3 months, the intervention patients were encouraged to practice daily meditation for 20 minutes alone or using video support material, with a weekly follow-up phone call. Assessments of stress, anxiety, and depression took place at baseline and after 4 months using the Perceived Stress Scale, Beck Anxiety Inventory, Beck Depression Inventory, and HeartQoL questionnaire.

At 4 months, individuals in the meditation group had reduced depression levels significantly, by 44%, compared with controls (P < .001). Anxiety and stress decreased significantly, by 30% (P = .04) and 31% (P = .05), respectively. After 4 months, individuals in the control group were offered the opportunity to follow the meditation protocol.

In addition, “the emotional dimension of quality of life increased by 60% in the intervention group,” Dr. Monteiro noted. However, physical QoL did not change between groups.

The study was limited by the small sample size, and more research is needed in larger and more diverse populations, Dr. Monteiro said. However, the results support the value of meditation as an adjunct component of care for CAD patients in a long-term rehabilitation program.
 

Motivation makes a difference

The current study is important as an exploration of “a straightforward, simple, low-risk approach that could be an adjunct to benefit patients with serious cardiovascular disease,” Brian Olshansky, MD, a cardiologist at the University of Iowa, Iowa City, said in an interview.

“We have moved into a time of polypharmacy and multiple interventions for patients with underlying cardiovascular disease which, in many cases, have proven benefit but also potential adverse effects,” he said. “Engaging patients to participate in their health care, when there is serious underlying cardiovascular disease, has potential beneficial impact in many ways. Meditation is a low-risk, low-cost, potentially beneficial adjunct to standard medical therapy that may enhance psychological outcomes as shown here in this small study.”

However, “patients often rely on high-cost, potentially high-risk therapeutic interventions, expecting complete control of their problems without their own collaborative intervention,” he noted.

Dr. Olshansky said he was not surprised by any of the findings, and would have been surprised if meditation had failed to show any benefit for the study population.

“I am very pleased to see these results and would encourage meditation practice to be part of cardiovascular rehabilitation for motivated individuals,” he said. “What did surprise me was the adherence to the meditation protocol for those who participated. This represents a highly motivated group and it may be difficult to expect the same results in less motivated individuals.”

The current study has several strengths, including the use of controls and high rates of adherence to the protocol, said Dr. Olshansky. Other strengths include the standardized approach and the reasonable quality of the outcome measures, which showed a substantial benefit.

However, “this is a small study of motivated individuals of whom 80% were male,” and generalizability to other populations is unclear, Dr. Olshansky said. In addition, the racial mix was not described, and the severity of the underlying coronary artery disease and the therapies provided to these individuals is not detailed. A sicker population may not fare as well.”

The reasons for the benefits of meditation remain uncertain, Dr. Olshansky said. “It could be, specifically, that the meditation itself has physiological effects that ultimately translate into psychosocial benefit. However, those who enrolled and were interested may have derived a placebo effect. In any case, benefit was achieved, but the crossover benefit to the control group is unclear.

“In other words, the statistical approach to benefit is uncertain as to when it was measured, but presumably before the control group was allowed to engage in a meditation practice,” and the follow-up was short term, said Dr. Olshansky.
 

Data support patient engagement

The message to clinicians and patients: “Patients should be engaged in their own health care when it comes to rehabilitation for cardiovascular disease,” said Dr. Olshansky. “Motivated individuals who are educated about a meditative practice performed in a standardized way will have improvement most likely in their quality of life, and when it comes to measurements of depression, stress and anxiety.”

Although the mechanisms behind the benefits remain unclear, “having a standardized credible prescription for which patients can become intimately engaged is beneficial,” he added.

The study received no outside funding. Neither Dr. Monteiro nor Dr. Olshansky had any financial conflicts to disclose.


 

Regular meditation reduced depression by roughly 44% in adults with coronary artery disease who were involved in a cardiovascular rehabilitation program.

An increasing body of research supports the impact of psychological risk factors including stress, personality type, anger, and hostility on conditions such as depression and anxiety, but also social isolation and low socioeconomic status, Ana Luisa Vitorino Monteiro, MD, of the University of Lisbon said in a presentation at the annual congress of the European Association of Preventive Cardiology. In addition, “stress, anxiety, and depression deteriorate the cardiovascular (CV) system through psycho-neuro-immunoendocrinology system and behavioral pathways.”

Meditation as a tool for stress management has been gaining popularity, but its use as part of a CV rehabilitation program as a complementary therapy has not been well studied, she added.

Dr. Monteiro and colleagues recruited 80 adults with CAD who were undergoing CV rehabilitation to join a meditation program. Of these, 48 accepted (60%) and 40% declined. Those who accepted were part of an exercise-based CV rehabilitation program that met three times a week for at least 6 months. The mean age of the participants was 65 years, and 80% were male.

Participants were randomized to an intervention group with a weekly 90-minute session that included breathing and meditation for 1 month in addition to usual care, or to usual care in the rehabilitation program. Over the next 3 months, the intervention patients were encouraged to practice daily meditation for 20 minutes alone or using video support material, with a weekly follow-up phone call. Assessments of stress, anxiety, and depression took place at baseline and after 4 months using the Perceived Stress Scale, Beck Anxiety Inventory, Beck Depression Inventory, and HeartQoL questionnaire.

At 4 months, individuals in the meditation group had reduced depression levels significantly, by 44%, compared with controls (P < .001). Anxiety and stress decreased significantly, by 30% (P = .04) and 31% (P = .05), respectively. After 4 months, individuals in the control group were offered the opportunity to follow the meditation protocol.

In addition, “the emotional dimension of quality of life increased by 60% in the intervention group,” Dr. Monteiro noted. However, physical QoL did not change between groups.

The study was limited by the small sample size, and more research is needed in larger and more diverse populations, Dr. Monteiro said. However, the results support the value of meditation as an adjunct component of care for CAD patients in a long-term rehabilitation program.
 

Motivation makes a difference

The current study is important as an exploration of “a straightforward, simple, low-risk approach that could be an adjunct to benefit patients with serious cardiovascular disease,” Brian Olshansky, MD, a cardiologist at the University of Iowa, Iowa City, said in an interview.

“We have moved into a time of polypharmacy and multiple interventions for patients with underlying cardiovascular disease which, in many cases, have proven benefit but also potential adverse effects,” he said. “Engaging patients to participate in their health care, when there is serious underlying cardiovascular disease, has potential beneficial impact in many ways. Meditation is a low-risk, low-cost, potentially beneficial adjunct to standard medical therapy that may enhance psychological outcomes as shown here in this small study.”

However, “patients often rely on high-cost, potentially high-risk therapeutic interventions, expecting complete control of their problems without their own collaborative intervention,” he noted.

Dr. Olshansky said he was not surprised by any of the findings, and would have been surprised if meditation had failed to show any benefit for the study population.

“I am very pleased to see these results and would encourage meditation practice to be part of cardiovascular rehabilitation for motivated individuals,” he said. “What did surprise me was the adherence to the meditation protocol for those who participated. This represents a highly motivated group and it may be difficult to expect the same results in less motivated individuals.”

The current study has several strengths, including the use of controls and high rates of adherence to the protocol, said Dr. Olshansky. Other strengths include the standardized approach and the reasonable quality of the outcome measures, which showed a substantial benefit.

However, “this is a small study of motivated individuals of whom 80% were male,” and generalizability to other populations is unclear, Dr. Olshansky said. In addition, the racial mix was not described, and the severity of the underlying coronary artery disease and the therapies provided to these individuals is not detailed. A sicker population may not fare as well.”

The reasons for the benefits of meditation remain uncertain, Dr. Olshansky said. “It could be, specifically, that the meditation itself has physiological effects that ultimately translate into psychosocial benefit. However, those who enrolled and were interested may have derived a placebo effect. In any case, benefit was achieved, but the crossover benefit to the control group is unclear.

“In other words, the statistical approach to benefit is uncertain as to when it was measured, but presumably before the control group was allowed to engage in a meditation practice,” and the follow-up was short term, said Dr. Olshansky.
 

Data support patient engagement

The message to clinicians and patients: “Patients should be engaged in their own health care when it comes to rehabilitation for cardiovascular disease,” said Dr. Olshansky. “Motivated individuals who are educated about a meditative practice performed in a standardized way will have improvement most likely in their quality of life, and when it comes to measurements of depression, stress and anxiety.”

Although the mechanisms behind the benefits remain unclear, “having a standardized credible prescription for which patients can become intimately engaged is beneficial,” he added.

The study received no outside funding. Neither Dr. Monteiro nor Dr. Olshansky had any financial conflicts to disclose.


 

Regular meditation reduced depression by roughly 44% in adults with coronary artery disease who were involved in a cardiovascular rehabilitation program.

An increasing body of research supports the impact of psychological risk factors including stress, personality type, anger, and hostility on conditions such as depression and anxiety, but also social isolation and low socioeconomic status, Ana Luisa Vitorino Monteiro, MD, of the University of Lisbon said in a presentation at the annual congress of the European Association of Preventive Cardiology. In addition, “stress, anxiety, and depression deteriorate the cardiovascular (CV) system through psycho-neuro-immunoendocrinology system and behavioral pathways.”

Meditation as a tool for stress management has been gaining popularity, but its use as part of a CV rehabilitation program as a complementary therapy has not been well studied, she added.

Dr. Monteiro and colleagues recruited 80 adults with CAD who were undergoing CV rehabilitation to join a meditation program. Of these, 48 accepted (60%) and 40% declined. Those who accepted were part of an exercise-based CV rehabilitation program that met three times a week for at least 6 months. The mean age of the participants was 65 years, and 80% were male.

Participants were randomized to an intervention group with a weekly 90-minute session that included breathing and meditation for 1 month in addition to usual care, or to usual care in the rehabilitation program. Over the next 3 months, the intervention patients were encouraged to practice daily meditation for 20 minutes alone or using video support material, with a weekly follow-up phone call. Assessments of stress, anxiety, and depression took place at baseline and after 4 months using the Perceived Stress Scale, Beck Anxiety Inventory, Beck Depression Inventory, and HeartQoL questionnaire.

At 4 months, individuals in the meditation group had reduced depression levels significantly, by 44%, compared with controls (P < .001). Anxiety and stress decreased significantly, by 30% (P = .04) and 31% (P = .05), respectively. After 4 months, individuals in the control group were offered the opportunity to follow the meditation protocol.

In addition, “the emotional dimension of quality of life increased by 60% in the intervention group,” Dr. Monteiro noted. However, physical QoL did not change between groups.

The study was limited by the small sample size, and more research is needed in larger and more diverse populations, Dr. Monteiro said. However, the results support the value of meditation as an adjunct component of care for CAD patients in a long-term rehabilitation program.
 

Motivation makes a difference

The current study is important as an exploration of “a straightforward, simple, low-risk approach that could be an adjunct to benefit patients with serious cardiovascular disease,” Brian Olshansky, MD, a cardiologist at the University of Iowa, Iowa City, said in an interview.

“We have moved into a time of polypharmacy and multiple interventions for patients with underlying cardiovascular disease which, in many cases, have proven benefit but also potential adverse effects,” he said. “Engaging patients to participate in their health care, when there is serious underlying cardiovascular disease, has potential beneficial impact in many ways. Meditation is a low-risk, low-cost, potentially beneficial adjunct to standard medical therapy that may enhance psychological outcomes as shown here in this small study.”

However, “patients often rely on high-cost, potentially high-risk therapeutic interventions, expecting complete control of their problems without their own collaborative intervention,” he noted.

Dr. Olshansky said he was not surprised by any of the findings, and would have been surprised if meditation had failed to show any benefit for the study population.

“I am very pleased to see these results and would encourage meditation practice to be part of cardiovascular rehabilitation for motivated individuals,” he said. “What did surprise me was the adherence to the meditation protocol for those who participated. This represents a highly motivated group and it may be difficult to expect the same results in less motivated individuals.”

The current study has several strengths, including the use of controls and high rates of adherence to the protocol, said Dr. Olshansky. Other strengths include the standardized approach and the reasonable quality of the outcome measures, which showed a substantial benefit.

However, “this is a small study of motivated individuals of whom 80% were male,” and generalizability to other populations is unclear, Dr. Olshansky said. In addition, the racial mix was not described, and the severity of the underlying coronary artery disease and the therapies provided to these individuals is not detailed. A sicker population may not fare as well.”

The reasons for the benefits of meditation remain uncertain, Dr. Olshansky said. “It could be, specifically, that the meditation itself has physiological effects that ultimately translate into psychosocial benefit. However, those who enrolled and were interested may have derived a placebo effect. In any case, benefit was achieved, but the crossover benefit to the control group is unclear.

“In other words, the statistical approach to benefit is uncertain as to when it was measured, but presumably before the control group was allowed to engage in a meditation practice,” and the follow-up was short term, said Dr. Olshansky.
 

Data support patient engagement

The message to clinicians and patients: “Patients should be engaged in their own health care when it comes to rehabilitation for cardiovascular disease,” said Dr. Olshansky. “Motivated individuals who are educated about a meditative practice performed in a standardized way will have improvement most likely in their quality of life, and when it comes to measurements of depression, stress and anxiety.”

Although the mechanisms behind the benefits remain unclear, “having a standardized credible prescription for which patients can become intimately engaged is beneficial,” he added.

The study received no outside funding. Neither Dr. Monteiro nor Dr. Olshansky had any financial conflicts to disclose.


 

NEW YORK – The Food and Drug Administration’s 2016 approval of the Bruton’s tyrosine kinase inhibitor ibrutinib (IB) as a frontline therapy for chronic lymphocytic leukemia (CLL) dramatically improved overall survival rates for patients with this condition. Follow-up data from 8 years after the RESONATE-2 trial indicated that patients with CLL (65 years or older) who remain on IB therapy can expect to live as long as someone in the general population.

Physicians now face two challenges in frontline CLL treatment: finding safe and effective drugs with fewer side effects, allowing patients to maintain therapy; and offering young or genomically high-risk patients treatments that reduce the risk of relapse.

courtesy Dr. Allan

“My preferred approach to CLL treatment is the use of second generation Bruton’s tyrosine kinase inhibitors, due to their improved toxicity profiles. These drugs are a great frontline option for most, if not all CLL patients,” said John N. Allan, associate professor at Weill Cornell Medicine, New York, in his presentation on frontline CLL treatments at the Great Debates and Updates Hematologic Malignancies Conference. “This is true even of older patients or those with comorbidities because this class of drug allows us to keep patients on treatment with excellent long-term outcomes.”

Results from the Alpine trial (NCT03734016), which included patients with and without high genomic risk, confirmed the superiority of the second generation Bruton’s tyrosine kinase inhibitor zanubrutinib (ZB) versus ibrutinib in terms of overall response rate 86.2% versus 75.5%, progression free survival 2-years after treatment 79.5% versus 67.3%, and adverse events (AEs) leading to discontinuation 15.4% versus 22.2% respectively.

The SEQUOIA trial (NCT03336333) demonstrated the effectiveness of ZB versus bendamustine + rituximab combination (BR) therapy in treatment-naive CLL / small lymphocytic leukemia patients with normal and high genomic risk. Overall 24-month progression free survival (PFS) was 85% in the ZB cohort vs. 69% in the BR cohort. This trend held true among high-risk subgroups like patients with an unmutated IgVH gene or 11q22.3 gene deletion.

Therapies known as “doublets” and “triplets” (which include a Bruton’s tyrosine kinase inhibitor in addition to other drugs) are not FDA approved for frontline CLL treatment. Yet studies suggest that young patients who are better able to tolerate AEs or high-risk patients with a greater risk of relapse (even on monotherapy maintenance), may derive benefits from multidrug frontline treatment.

“With doublets and triplets, doctors add treatment intensity up front so that patients can have a fixed duration of therapy versus continuous indefinite therapy,” said Vu Nguyen MD, a hematologist at Oakland (Calif.) Medical Center. “This is encouraging because if you can have a fixed duration of treatment, patients can come off treatment agents and hopefully have a prolonged remission and normal lifespan without chronic therapy and side effects.”

The CAPTIVATE study confirmed this approach with 3 cycles of IB followed by 12 cycles of IB + venetoclax leading to a 24-month PFS rate of 94% in patients with high risk or relapse. “Furthermore, 95% of study participants patients less than 70 years old completed 12 months of combination treatment without major problems,” said Dr. Allan. He concluded his remarks by noting that “we need longer term data on the use of combination therapy for frontline CLL treatment to confirm if and when it should be used.”

Dr. Allan disclosed relationships with Adaptive Biotechnologies, ADC Therapeutics, AstraZeneca, BeiGene, Epizyme, Genentech, Janssen, Lilly, Pharmacyclics, and TG Therapeutics. Dr. Nguyen reported no disclosures.

NEW YORK – The Food and Drug Administration’s 2016 approval of the Bruton’s tyrosine kinase inhibitor ibrutinib (IB) as a frontline therapy for chronic lymphocytic leukemia (CLL) dramatically improved overall survival rates for patients with this condition. Follow-up data from 8 years after the RESONATE-2 trial indicated that patients with CLL (65 years or older) who remain on IB therapy can expect to live as long as someone in the general population.

Physicians now face two challenges in frontline CLL treatment: finding safe and effective drugs with fewer side effects, allowing patients to maintain therapy; and offering young or genomically high-risk patients treatments that reduce the risk of relapse.

courtesy Dr. Allan

“My preferred approach to CLL treatment is the use of second generation Bruton’s tyrosine kinase inhibitors, due to their improved toxicity profiles. These drugs are a great frontline option for most, if not all CLL patients,” said John N. Allan, associate professor at Weill Cornell Medicine, New York, in his presentation on frontline CLL treatments at the Great Debates and Updates Hematologic Malignancies Conference. “This is true even of older patients or those with comorbidities because this class of drug allows us to keep patients on treatment with excellent long-term outcomes.”

Results from the Alpine trial (NCT03734016), which included patients with and without high genomic risk, confirmed the superiority of the second generation Bruton’s tyrosine kinase inhibitor zanubrutinib (ZB) versus ibrutinib in terms of overall response rate 86.2% versus 75.5%, progression free survival 2-years after treatment 79.5% versus 67.3%, and adverse events (AEs) leading to discontinuation 15.4% versus 22.2% respectively.

The SEQUOIA trial (NCT03336333) demonstrated the effectiveness of ZB versus bendamustine + rituximab combination (BR) therapy in treatment-naive CLL / small lymphocytic leukemia patients with normal and high genomic risk. Overall 24-month progression free survival (PFS) was 85% in the ZB cohort vs. 69% in the BR cohort. This trend held true among high-risk subgroups like patients with an unmutated IgVH gene or 11q22.3 gene deletion.

Therapies known as “doublets” and “triplets” (which include a Bruton’s tyrosine kinase inhibitor in addition to other drugs) are not FDA approved for frontline CLL treatment. Yet studies suggest that young patients who are better able to tolerate AEs or high-risk patients with a greater risk of relapse (even on monotherapy maintenance), may derive benefits from multidrug frontline treatment.

“With doublets and triplets, doctors add treatment intensity up front so that patients can have a fixed duration of therapy versus continuous indefinite therapy,” said Vu Nguyen MD, a hematologist at Oakland (Calif.) Medical Center. “This is encouraging because if you can have a fixed duration of treatment, patients can come off treatment agents and hopefully have a prolonged remission and normal lifespan without chronic therapy and side effects.”

The CAPTIVATE study confirmed this approach with 3 cycles of IB followed by 12 cycles of IB + venetoclax leading to a 24-month PFS rate of 94% in patients with high risk or relapse. “Furthermore, 95% of study participants patients less than 70 years old completed 12 months of combination treatment without major problems,” said Dr. Allan. He concluded his remarks by noting that “we need longer term data on the use of combination therapy for frontline CLL treatment to confirm if and when it should be used.”

Dr. Allan disclosed relationships with Adaptive Biotechnologies, ADC Therapeutics, AstraZeneca, BeiGene, Epizyme, Genentech, Janssen, Lilly, Pharmacyclics, and TG Therapeutics. Dr. Nguyen reported no disclosures.

NEW YORK – The Food and Drug Administration’s 2016 approval of the Bruton’s tyrosine kinase inhibitor ibrutinib (IB) as a frontline therapy for chronic lymphocytic leukemia (CLL) dramatically improved overall survival rates for patients with this condition. Follow-up data from 8 years after the RESONATE-2 trial indicated that patients with CLL (65 years or older) who remain on IB therapy can expect to live as long as someone in the general population.

Physicians now face two challenges in frontline CLL treatment: finding safe and effective drugs with fewer side effects, allowing patients to maintain therapy; and offering young or genomically high-risk patients treatments that reduce the risk of relapse.

courtesy Dr. Allan

“My preferred approach to CLL treatment is the use of second generation Bruton’s tyrosine kinase inhibitors, due to their improved toxicity profiles. These drugs are a great frontline option for most, if not all CLL patients,” said John N. Allan, associate professor at Weill Cornell Medicine, New York, in his presentation on frontline CLL treatments at the Great Debates and Updates Hematologic Malignancies Conference. “This is true even of older patients or those with comorbidities because this class of drug allows us to keep patients on treatment with excellent long-term outcomes.”

Results from the Alpine trial (NCT03734016), which included patients with and without high genomic risk, confirmed the superiority of the second generation Bruton’s tyrosine kinase inhibitor zanubrutinib (ZB) versus ibrutinib in terms of overall response rate 86.2% versus 75.5%, progression free survival 2-years after treatment 79.5% versus 67.3%, and adverse events (AEs) leading to discontinuation 15.4% versus 22.2% respectively.

The SEQUOIA trial (NCT03336333) demonstrated the effectiveness of ZB versus bendamustine + rituximab combination (BR) therapy in treatment-naive CLL / small lymphocytic leukemia patients with normal and high genomic risk. Overall 24-month progression free survival (PFS) was 85% in the ZB cohort vs. 69% in the BR cohort. This trend held true among high-risk subgroups like patients with an unmutated IgVH gene or 11q22.3 gene deletion.

Therapies known as “doublets” and “triplets” (which include a Bruton’s tyrosine kinase inhibitor in addition to other drugs) are not FDA approved for frontline CLL treatment. Yet studies suggest that young patients who are better able to tolerate AEs or high-risk patients with a greater risk of relapse (even on monotherapy maintenance), may derive benefits from multidrug frontline treatment.

“With doublets and triplets, doctors add treatment intensity up front so that patients can have a fixed duration of therapy versus continuous indefinite therapy,” said Vu Nguyen MD, a hematologist at Oakland (Calif.) Medical Center. “This is encouraging because if you can have a fixed duration of treatment, patients can come off treatment agents and hopefully have a prolonged remission and normal lifespan without chronic therapy and side effects.”

The CAPTIVATE study confirmed this approach with 3 cycles of IB followed by 12 cycles of IB + venetoclax leading to a 24-month PFS rate of 94% in patients with high risk or relapse. “Furthermore, 95% of study participants patients less than 70 years old completed 12 months of combination treatment without major problems,” said Dr. Allan. He concluded his remarks by noting that “we need longer term data on the use of combination therapy for frontline CLL treatment to confirm if and when it should be used.”

Dr. Allan disclosed relationships with Adaptive Biotechnologies, ADC Therapeutics, AstraZeneca, BeiGene, Epizyme, Genentech, Janssen, Lilly, Pharmacyclics, and TG Therapeutics. Dr. Nguyen reported no disclosures.

PHOENIX – Burns, dyspigmentation, and scarring were the three most common complications from the use of ablative and nonablative fractional resurfacing lasers reported to the Food and Drug Administration between 2013 and 2022, an analysis of medical device reports (MDRs) over a decade showed.

Dr. Hashemi

The researchers limited their query to MDRs related to ablative and nonablative fractional resurfacing lasers over the 10-year period from 2013 to 2022. The query was performed in January 2023 using a comprehensive list of product names and manufacturers.

The initial search yielded 240 MDRs, which were individually reviewed for duplicate records or insufficient data, and the final analysis included 165 MDRs. The 10 most reported adverse events were burns (30%), followed by dyspigmentation (14%), scarring (12%), other (11%), postoperative infection (8%), blisters (6%), pain (5%), hypertrophic scar (4%), post-treatment inflammation (4%), and textural changes (3%). Within the 10-year period analyzed, 56% of MDRs occurred between 2016 and 2019, with a disproportionately low percentage of MDRs occurring in 2022 (5%).

“Adverse events due to ablative and nonablative fractional resurfacing lasers are rare but potentially serious,” Dr. Hashemi concluded. “Care must be taken with counseling, patient selection, and treatment settings to optimize safety, informed consent, and patient satisfaction. Given the relatively low number of adverse events seen with fractional resurfacing lasers, factors driving their safety should be further explored.”

He added that he was surprised by the relatively low number of reported issues, referring to the total of 165 cases over 10 years. By comparison, he said, body contouring had 660 cases reported over a 7-year period in one recent study.

According to the MAUDE website, submitting MDRs to MAUDE is mandatory for manufacturers, importers, and device user facilities, and are voluntary for other groups, such as health care professionals, patients, and consumers.

Dr. Hashemi disclosed that he is a consultant for Castle Biosciences. He is also an entrepreneur in residence for Gore Range Capital.

PHOENIX – Burns, dyspigmentation, and scarring were the three most common complications from the use of ablative and nonablative fractional resurfacing lasers reported to the Food and Drug Administration between 2013 and 2022, an analysis of medical device reports (MDRs) over a decade showed.

Dr. Hashemi

The researchers limited their query to MDRs related to ablative and nonablative fractional resurfacing lasers over the 10-year period from 2013 to 2022. The query was performed in January 2023 using a comprehensive list of product names and manufacturers.

The initial search yielded 240 MDRs, which were individually reviewed for duplicate records or insufficient data, and the final analysis included 165 MDRs. The 10 most reported adverse events were burns (30%), followed by dyspigmentation (14%), scarring (12%), other (11%), postoperative infection (8%), blisters (6%), pain (5%), hypertrophic scar (4%), post-treatment inflammation (4%), and textural changes (3%). Within the 10-year period analyzed, 56% of MDRs occurred between 2016 and 2019, with a disproportionately low percentage of MDRs occurring in 2022 (5%).

“Adverse events due to ablative and nonablative fractional resurfacing lasers are rare but potentially serious,” Dr. Hashemi concluded. “Care must be taken with counseling, patient selection, and treatment settings to optimize safety, informed consent, and patient satisfaction. Given the relatively low number of adverse events seen with fractional resurfacing lasers, factors driving their safety should be further explored.”

He added that he was surprised by the relatively low number of reported issues, referring to the total of 165 cases over 10 years. By comparison, he said, body contouring had 660 cases reported over a 7-year period in one recent study.

According to the MAUDE website, submitting MDRs to MAUDE is mandatory for manufacturers, importers, and device user facilities, and are voluntary for other groups, such as health care professionals, patients, and consumers.

Dr. Hashemi disclosed that he is a consultant for Castle Biosciences. He is also an entrepreneur in residence for Gore Range Capital.

PHOENIX – Burns, dyspigmentation, and scarring were the three most common complications from the use of ablative and nonablative fractional resurfacing lasers reported to the Food and Drug Administration between 2013 and 2022, an analysis of medical device reports (MDRs) over a decade showed.

Dr. Hashemi

The researchers limited their query to MDRs related to ablative and nonablative fractional resurfacing lasers over the 10-year period from 2013 to 2022. The query was performed in January 2023 using a comprehensive list of product names and manufacturers.

The initial search yielded 240 MDRs, which were individually reviewed for duplicate records or insufficient data, and the final analysis included 165 MDRs. The 10 most reported adverse events were burns (30%), followed by dyspigmentation (14%), scarring (12%), other (11%), postoperative infection (8%), blisters (6%), pain (5%), hypertrophic scar (4%), post-treatment inflammation (4%), and textural changes (3%). Within the 10-year period analyzed, 56% of MDRs occurred between 2016 and 2019, with a disproportionately low percentage of MDRs occurring in 2022 (5%).

“Adverse events due to ablative and nonablative fractional resurfacing lasers are rare but potentially serious,” Dr. Hashemi concluded. “Care must be taken with counseling, patient selection, and treatment settings to optimize safety, informed consent, and patient satisfaction. Given the relatively low number of adverse events seen with fractional resurfacing lasers, factors driving their safety should be further explored.”

He added that he was surprised by the relatively low number of reported issues, referring to the total of 165 cases over 10 years. By comparison, he said, body contouring had 660 cases reported over a 7-year period in one recent study.

According to the MAUDE website, submitting MDRs to MAUDE is mandatory for manufacturers, importers, and device user facilities, and are voluntary for other groups, such as health care professionals, patients, and consumers.

Dr. Hashemi disclosed that he is a consultant for Castle Biosciences. He is also an entrepreneur in residence for Gore Range Capital.

The combination of a patient-specific mRNA-based cancer vaccine (mRNA-4157/V940, Moderna and Merck) and the immune checkpoint inhibitor pembrolizumab significantly improved recurrence-free survival for patients with high-risk melanoma compared with pembrolizumab alone, according to the latest data from the KEYNOTE-942 trial.

This recurrence-free survival benefit corresponded to a 44% reduced risk of recurrence or death in patients who received the personalized vaccine plus pembrolizumab compared with the immunotherapy alone.

The randomized phase 2b trial is the first to show a positive result for a cancer vaccine in a randomized trial. The results, if confirmed in further studies, hold promise for treating other solid tumors with sensitivity to the programmed death-1 (PD-1) protein, investigators said.

“KEYNOTE-942 is the first randomized study to demonstrate improvement in recurrence-free survival in melanoma, or in any cancer in my view, with an individualized neoantigen vaccine approach,” trial investigator Jeffrey S. Weber, MD, PhD, of NYU Langone Perlmutter Cancer Center in New York, said during an oral abstract session at the annual meeting of the American Association for Cancer Research.

“I have every confidence that this strategy will be expanded to other histologies that are PD-1 sensitive, such as non–small cell lung cancer, renal cell cancer, hepatocellular cancer, gastroesophageal cancer, et cetera,” Dr. Weber said.

Invited discussant Margaret Callahan, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, called the results “exciting,” especially in light of previous results in cancer vaccine trials. “Despite hundreds of formulations and dozens of studies, cancer vaccines have been disappointing so far, and have largely failed to have a meaningful impact in oncology,” she said.
 

A promising personalized vaccine

The mRNA vaccine is individually tailored and encodes up to 34 patient-specific tumor neoantigens. The vaccine also acts as an adjuvant to strengthen the immune response.

Dr. Weber said that the “mRNA 4157 is what one would call an individualized neoantigen therapy. It will target an individual patient’s unique tumor mutations, and the revelation over the last 5-10 years, is that, for better or worse, virtually all the neoantigens are unique to an individual patient. There are very, very few true universal neoantigens, or at least universal neoantigens that could have clinical utility.”

The vaccines are developed from tumor biopsy tissues that then undergo whole exome and RNA sequencing to identify single nucleotide variants that are present in the tumor but not in normal tissue.

The findings are then fed into a computer algorithm that identifies potential neoepitope peptides that would bind well to the patient’s human leukocyte antigen (HLA) type and could evoke strong T-cell responses.

“Once they’re chosen, you concatenate the sequences together into a single-strand mRNA vaccine, it’s packaged with nanoparticles to encapsulate it, and there you have your mRNA vaccine,” Dr. Weber explained.

In the KEYNOTE-942 trial, the investigators randomly assigned patients with completely resected high-risk cutaneous melanoma on a 2:1 basis to receive mRNA-4157 via intramuscular injection every 3 weeks for a total of nine doses, plus intravenous pembrolizumab every 3 weeks for 18 cycles (107 patients) or pembrolizumab alone (50 patients). Median follow-up was 101 weeks in the combination group and 105 weeks in the pembrolizumab group.

Overall, the 18-month recurrence-free survival rates were 78.6% in the combination arm and 62.2% in the pembrolizumab arm. The recurrence-free survival rates corresponded to a 44% reduced risk of recurrence or death in patients who received the personalized vaccine plus pembrolizumab compared with those who received only pembrolizumab (hazard ratio [HR] for recurrence, 0.561; P =.0266).

Grade 3 or greater adverse events occurred in 25% of patients in the combination group and 18% of patients in the pembrolizumab group. The most common grade 3 event associated with the vaccine was fatigue. No grade 4 adverse events or deaths were associated with the vaccine, and the addition of the vaccine to pembrolizumab did not appear to increase risk for immune-mediated adverse events.

In a subanalysis, Dr. Weber and colleagues explored the relationship between tumor mutational burden and recurrence-free survival. Higher tumor mutational burden may mean more neoepitopes to target, which is helpful when developing personalized neoantigen vaccines, explained coinvestigator Ryan Sullivan, MD, associate director of the melanoma program at Mass General Cancer Center, Boston, who presented the subanalysis results.

The investigators performed whole exome and whole transcriptome sequencing of baseline tumor biopsy samples to determine the mutational burden of tumors and defined a high mutational burden as 10 or more mutations per megabase.

Overall, in the combination group, patients with a higher tumor mutational burden at baseline showed improved outcomes (HR, 0.652; 95% confidence interval [CI], 0.284-1.494), as did patients with a lower tumor mutational burden (HR, 0.586; 95% CI, 0.243-1.415).

The authors found the same was true for patients with high vs. low tumor inflammation scores (high: HR, 0.576; 95% CI, 0.209-1.591 vs. low: HR, 0.528; 95% CI, 0.253-1.101) and higher PD-L1 expression (PD-L1 positive: HR, 0.485; 95% CI, 0.226-1.039 vs. PD-L1 negative: HR, 0.162; 95% CI, 0.038-0.685).

The hazard ratios crossed 1, which suggest that the combination was similarly effective in all patient subsets, said Dr. Sullivan.

Dr. Callahan also highlighted that the P value was based on a one-side log-rank test, “a relatively low bar to jump over” and that there were slight imbalances in both PD-1 expression status and tumor mutational burden – both of which favored the vaccine group and may be associated with better recurrence-free survival.

The 16% difference in recurrence-free survival seen with the combination vs. pembrolizumab alone, if confirmed in further studies, “is clinically meaningful for high-risk patients,” said Dr. Callahan. “The authors are to be congratulated for presenting the first randomized study of a neoantigen vaccine with a clinical efficacy primary endpoint, and this is a trial that incorporates many of the lessons we’ve learned along the years.”

Dr. Sullivan also commented on the promising results. “The field of cancer vaccines is a wasteland of failed clinical trials after some initial promising data, so to have something like this where it does appear that this vaccine strategy works is good not only for patients with melanoma but for those people who have dedicated their lives to trying to develop cancer vaccines,” he said in an interview.

KEYNOTE-942 was funded by Moderna with collaboration from Merck. Dr. Weber has financial relationships with Merck, Moderna, and other companies. Dr. Sullivan has served as a paid consultant for Merck and has received research funding from the company. Dr. Callahan disclosed a consulting/advisory role with Moderna, Merck, and others.
 

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

The combination of a patient-specific mRNA-based cancer vaccine (mRNA-4157/V940, Moderna and Merck) and the immune checkpoint inhibitor pembrolizumab significantly improved recurrence-free survival for patients with high-risk melanoma compared with pembrolizumab alone, according to the latest data from the KEYNOTE-942 trial.

This recurrence-free survival benefit corresponded to a 44% reduced risk of recurrence or death in patients who received the personalized vaccine plus pembrolizumab compared with the immunotherapy alone.

The randomized phase 2b trial is the first to show a positive result for a cancer vaccine in a randomized trial. The results, if confirmed in further studies, hold promise for treating other solid tumors with sensitivity to the programmed death-1 (PD-1) protein, investigators said.

“KEYNOTE-942 is the first randomized study to demonstrate improvement in recurrence-free survival in melanoma, or in any cancer in my view, with an individualized neoantigen vaccine approach,” trial investigator Jeffrey S. Weber, MD, PhD, of NYU Langone Perlmutter Cancer Center in New York, said during an oral abstract session at the annual meeting of the American Association for Cancer Research.

“I have every confidence that this strategy will be expanded to other histologies that are PD-1 sensitive, such as non–small cell lung cancer, renal cell cancer, hepatocellular cancer, gastroesophageal cancer, et cetera,” Dr. Weber said.

Invited discussant Margaret Callahan, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, called the results “exciting,” especially in light of previous results in cancer vaccine trials. “Despite hundreds of formulations and dozens of studies, cancer vaccines have been disappointing so far, and have largely failed to have a meaningful impact in oncology,” she said.
 

A promising personalized vaccine

The mRNA vaccine is individually tailored and encodes up to 34 patient-specific tumor neoantigens. The vaccine also acts as an adjuvant to strengthen the immune response.

Dr. Weber said that the “mRNA 4157 is what one would call an individualized neoantigen therapy. It will target an individual patient’s unique tumor mutations, and the revelation over the last 5-10 years, is that, for better or worse, virtually all the neoantigens are unique to an individual patient. There are very, very few true universal neoantigens, or at least universal neoantigens that could have clinical utility.”

The vaccines are developed from tumor biopsy tissues that then undergo whole exome and RNA sequencing to identify single nucleotide variants that are present in the tumor but not in normal tissue.

The findings are then fed into a computer algorithm that identifies potential neoepitope peptides that would bind well to the patient’s human leukocyte antigen (HLA) type and could evoke strong T-cell responses.

“Once they’re chosen, you concatenate the sequences together into a single-strand mRNA vaccine, it’s packaged with nanoparticles to encapsulate it, and there you have your mRNA vaccine,” Dr. Weber explained.

In the KEYNOTE-942 trial, the investigators randomly assigned patients with completely resected high-risk cutaneous melanoma on a 2:1 basis to receive mRNA-4157 via intramuscular injection every 3 weeks for a total of nine doses, plus intravenous pembrolizumab every 3 weeks for 18 cycles (107 patients) or pembrolizumab alone (50 patients). Median follow-up was 101 weeks in the combination group and 105 weeks in the pembrolizumab group.

Overall, the 18-month recurrence-free survival rates were 78.6% in the combination arm and 62.2% in the pembrolizumab arm. The recurrence-free survival rates corresponded to a 44% reduced risk of recurrence or death in patients who received the personalized vaccine plus pembrolizumab compared with those who received only pembrolizumab (hazard ratio [HR] for recurrence, 0.561; P =.0266).

Grade 3 or greater adverse events occurred in 25% of patients in the combination group and 18% of patients in the pembrolizumab group. The most common grade 3 event associated with the vaccine was fatigue. No grade 4 adverse events or deaths were associated with the vaccine, and the addition of the vaccine to pembrolizumab did not appear to increase risk for immune-mediated adverse events.

In a subanalysis, Dr. Weber and colleagues explored the relationship between tumor mutational burden and recurrence-free survival. Higher tumor mutational burden may mean more neoepitopes to target, which is helpful when developing personalized neoantigen vaccines, explained coinvestigator Ryan Sullivan, MD, associate director of the melanoma program at Mass General Cancer Center, Boston, who presented the subanalysis results.

The investigators performed whole exome and whole transcriptome sequencing of baseline tumor biopsy samples to determine the mutational burden of tumors and defined a high mutational burden as 10 or more mutations per megabase.

Overall, in the combination group, patients with a higher tumor mutational burden at baseline showed improved outcomes (HR, 0.652; 95% confidence interval [CI], 0.284-1.494), as did patients with a lower tumor mutational burden (HR, 0.586; 95% CI, 0.243-1.415).

The authors found the same was true for patients with high vs. low tumor inflammation scores (high: HR, 0.576; 95% CI, 0.209-1.591 vs. low: HR, 0.528; 95% CI, 0.253-1.101) and higher PD-L1 expression (PD-L1 positive: HR, 0.485; 95% CI, 0.226-1.039 vs. PD-L1 negative: HR, 0.162; 95% CI, 0.038-0.685).

The hazard ratios crossed 1, which suggest that the combination was similarly effective in all patient subsets, said Dr. Sullivan.

Dr. Callahan also highlighted that the P value was based on a one-side log-rank test, “a relatively low bar to jump over” and that there were slight imbalances in both PD-1 expression status and tumor mutational burden – both of which favored the vaccine group and may be associated with better recurrence-free survival.

The 16% difference in recurrence-free survival seen with the combination vs. pembrolizumab alone, if confirmed in further studies, “is clinically meaningful for high-risk patients,” said Dr. Callahan. “The authors are to be congratulated for presenting the first randomized study of a neoantigen vaccine with a clinical efficacy primary endpoint, and this is a trial that incorporates many of the lessons we’ve learned along the years.”

Dr. Sullivan also commented on the promising results. “The field of cancer vaccines is a wasteland of failed clinical trials after some initial promising data, so to have something like this where it does appear that this vaccine strategy works is good not only for patients with melanoma but for those people who have dedicated their lives to trying to develop cancer vaccines,” he said in an interview.

KEYNOTE-942 was funded by Moderna with collaboration from Merck. Dr. Weber has financial relationships with Merck, Moderna, and other companies. Dr. Sullivan has served as a paid consultant for Merck and has received research funding from the company. Dr. Callahan disclosed a consulting/advisory role with Moderna, Merck, and others.
 

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

The combination of a patient-specific mRNA-based cancer vaccine (mRNA-4157/V940, Moderna and Merck) and the immune checkpoint inhibitor pembrolizumab significantly improved recurrence-free survival for patients with high-risk melanoma compared with pembrolizumab alone, according to the latest data from the KEYNOTE-942 trial.

This recurrence-free survival benefit corresponded to a 44% reduced risk of recurrence or death in patients who received the personalized vaccine plus pembrolizumab compared with the immunotherapy alone.

The randomized phase 2b trial is the first to show a positive result for a cancer vaccine in a randomized trial. The results, if confirmed in further studies, hold promise for treating other solid tumors with sensitivity to the programmed death-1 (PD-1) protein, investigators said.

“KEYNOTE-942 is the first randomized study to demonstrate improvement in recurrence-free survival in melanoma, or in any cancer in my view, with an individualized neoantigen vaccine approach,” trial investigator Jeffrey S. Weber, MD, PhD, of NYU Langone Perlmutter Cancer Center in New York, said during an oral abstract session at the annual meeting of the American Association for Cancer Research.

“I have every confidence that this strategy will be expanded to other histologies that are PD-1 sensitive, such as non–small cell lung cancer, renal cell cancer, hepatocellular cancer, gastroesophageal cancer, et cetera,” Dr. Weber said.

Invited discussant Margaret Callahan, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, called the results “exciting,” especially in light of previous results in cancer vaccine trials. “Despite hundreds of formulations and dozens of studies, cancer vaccines have been disappointing so far, and have largely failed to have a meaningful impact in oncology,” she said.
 

A promising personalized vaccine

The mRNA vaccine is individually tailored and encodes up to 34 patient-specific tumor neoantigens. The vaccine also acts as an adjuvant to strengthen the immune response.

Dr. Weber said that the “mRNA 4157 is what one would call an individualized neoantigen therapy. It will target an individual patient’s unique tumor mutations, and the revelation over the last 5-10 years, is that, for better or worse, virtually all the neoantigens are unique to an individual patient. There are very, very few true universal neoantigens, or at least universal neoantigens that could have clinical utility.”

The vaccines are developed from tumor biopsy tissues that then undergo whole exome and RNA sequencing to identify single nucleotide variants that are present in the tumor but not in normal tissue.

The findings are then fed into a computer algorithm that identifies potential neoepitope peptides that would bind well to the patient’s human leukocyte antigen (HLA) type and could evoke strong T-cell responses.

“Once they’re chosen, you concatenate the sequences together into a single-strand mRNA vaccine, it’s packaged with nanoparticles to encapsulate it, and there you have your mRNA vaccine,” Dr. Weber explained.

In the KEYNOTE-942 trial, the investigators randomly assigned patients with completely resected high-risk cutaneous melanoma on a 2:1 basis to receive mRNA-4157 via intramuscular injection every 3 weeks for a total of nine doses, plus intravenous pembrolizumab every 3 weeks for 18 cycles (107 patients) or pembrolizumab alone (50 patients). Median follow-up was 101 weeks in the combination group and 105 weeks in the pembrolizumab group.

Overall, the 18-month recurrence-free survival rates were 78.6% in the combination arm and 62.2% in the pembrolizumab arm. The recurrence-free survival rates corresponded to a 44% reduced risk of recurrence or death in patients who received the personalized vaccine plus pembrolizumab compared with those who received only pembrolizumab (hazard ratio [HR] for recurrence, 0.561; P =.0266).

Grade 3 or greater adverse events occurred in 25% of patients in the combination group and 18% of patients in the pembrolizumab group. The most common grade 3 event associated with the vaccine was fatigue. No grade 4 adverse events or deaths were associated with the vaccine, and the addition of the vaccine to pembrolizumab did not appear to increase risk for immune-mediated adverse events.

In a subanalysis, Dr. Weber and colleagues explored the relationship between tumor mutational burden and recurrence-free survival. Higher tumor mutational burden may mean more neoepitopes to target, which is helpful when developing personalized neoantigen vaccines, explained coinvestigator Ryan Sullivan, MD, associate director of the melanoma program at Mass General Cancer Center, Boston, who presented the subanalysis results.

The investigators performed whole exome and whole transcriptome sequencing of baseline tumor biopsy samples to determine the mutational burden of tumors and defined a high mutational burden as 10 or more mutations per megabase.

Overall, in the combination group, patients with a higher tumor mutational burden at baseline showed improved outcomes (HR, 0.652; 95% confidence interval [CI], 0.284-1.494), as did patients with a lower tumor mutational burden (HR, 0.586; 95% CI, 0.243-1.415).

The authors found the same was true for patients with high vs. low tumor inflammation scores (high: HR, 0.576; 95% CI, 0.209-1.591 vs. low: HR, 0.528; 95% CI, 0.253-1.101) and higher PD-L1 expression (PD-L1 positive: HR, 0.485; 95% CI, 0.226-1.039 vs. PD-L1 negative: HR, 0.162; 95% CI, 0.038-0.685).

The hazard ratios crossed 1, which suggest that the combination was similarly effective in all patient subsets, said Dr. Sullivan.

Dr. Callahan also highlighted that the P value was based on a one-side log-rank test, “a relatively low bar to jump over” and that there were slight imbalances in both PD-1 expression status and tumor mutational burden – both of which favored the vaccine group and may be associated with better recurrence-free survival.

The 16% difference in recurrence-free survival seen with the combination vs. pembrolizumab alone, if confirmed in further studies, “is clinically meaningful for high-risk patients,” said Dr. Callahan. “The authors are to be congratulated for presenting the first randomized study of a neoantigen vaccine with a clinical efficacy primary endpoint, and this is a trial that incorporates many of the lessons we’ve learned along the years.”

Dr. Sullivan also commented on the promising results. “The field of cancer vaccines is a wasteland of failed clinical trials after some initial promising data, so to have something like this where it does appear that this vaccine strategy works is good not only for patients with melanoma but for those people who have dedicated their lives to trying to develop cancer vaccines,” he said in an interview.

KEYNOTE-942 was funded by Moderna with collaboration from Merck. Dr. Weber has financial relationships with Merck, Moderna, and other companies. Dr. Sullivan has served as a paid consultant for Merck and has received research funding from the company. Dr. Callahan disclosed a consulting/advisory role with Moderna, Merck, and others.
 

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

Black patients with cancer are significantly more likely to experience cardiotoxicity and heart failure related to chemotherapy than White cancer patients are, a research review indicates.

“It’s important that both patients and clinicians be aware of these disparities so that more meaningful conversations around long-term cardiac health and cancer treatment can take place,” lead investigator Wondewossen Gebeyehu, with the University of Toronto, said in an interview.

However, patients “should not avoid chemotherapy, as the most important thing is making sure they get the best cancer treatment possible, and studies already show Black patients may get less optimal cancer treatments,” Mr. Gebeyehu added in a statement.

Ana Barac, MD, PHD, chair of cardio-oncology at Inova Schar Cancer Institute and Inova Heart and Vascular Institute, Fairfax, Va., who wasn’t involved in the study, agreed.

“The most important message is to look at preexisting cardiovascular disease, oncology diagnosis, and be aware of existing disparities in a specific cancer and CVD,” Barac said in an interview.

“What should NOT happen is to overinterpret this report of cardiotoxicity as an indication to modify/avoid planned cancer treatment to decrease cardiotoxicity. This approach could worsen oncology outcomes and lead to undertreatment of cancer, therefore posing real danger,” said Dr. Barac.

The study was presented at the American College of Cardiology Advancing the Cardiovascular Care of the Oncology Patient 2023 conference.
 

Causes unclear

Chemotherapy is known to increase the risk of cardiovascular heart failure and other forms of CVD, but less is known about racial disparities in the incidence of chemotherapy-induced cardiotoxicity.

Mr. Gebeyehu and colleagues conducted a systematic review and meta-analysis of the available literature to assess racial disparities in CV adverse effects among cancer patients who were treated with chemotherapeutic agents. They screened 7,057 studies, fully reviewed 57, and included 24 studies, representing 683,749 participants, in their analysis.

Breast cancer was the most commonly reported malignancy. Other common malignancies were prostate, kidney, and hematologic malignancies such as leukemia and lymphoma.

Chemotherapeutic agents included anthracyclines (doxorubicin, daunorubicin), trastuzumab, and hormonal therapies.

Black race or African ancestry was associated with increased odds of chemotherapy-associated cardiotoxicity (odds ratio, 1.71; 95% confidence interval, 1.40-2.10), as well as congestive heart failure (OR, 1.92; 95% CI, 1.68-2.19).

Mr. Gebeyehu said in an interview that it’s hard to speculate on causation with an analysis of preexisting data such as this. “Our initial analysis that we’ve reported on so far are unadjusted values, meaning they don’t adjust for those potential underlying factors,” he noted.

“However, some of the studies individually controlled for socioeconomic factors and still found increased vulnerability to chemotherapy-associated cardiotoxicity in patients of Black race or African ancestry,” Mr. Gebeyehu said.

“It’s certainly possible that a mix of both biological and socioeconomic factors are interacting to lead to these disparities. One example could be the underrepresentation of Black patients in clinical trials to develop drugs. These could lead to chemotherapeutic agents being poorly optimized in this population relative to other racial/ethnic groups,” he added.

Dr. Barac said this study adds to the growing body of evidence about the importance of racial disparities in CVD and cancer outcomes.

“It is important to note that only the unadjusted odds ratio was reported and that much more detail is needed to understand what may be underlying the disparities. It is critically important to await the adjusted analysis, as well as details of the type of cancers and treatment used, before clinical implications can be discussed,” said Dr. Barac, who served as codirector of the conference.

“The risk of cardiotoxicity needs to be presented in the context of the oncology and CV disease burden, as both can influence the risk, and there could be a synergistic effect of disparities,” Dr. Barac added.

The study had no specific funding. Mr. Gebeyehu and Dr. Barac disclosed no relevant conflicts of interest.

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

Black patients with cancer are significantly more likely to experience cardiotoxicity and heart failure related to chemotherapy than White cancer patients are, a research review indicates.

“It’s important that both patients and clinicians be aware of these disparities so that more meaningful conversations around long-term cardiac health and cancer treatment can take place,” lead investigator Wondewossen Gebeyehu, with the University of Toronto, said in an interview.

However, patients “should not avoid chemotherapy, as the most important thing is making sure they get the best cancer treatment possible, and studies already show Black patients may get less optimal cancer treatments,” Mr. Gebeyehu added in a statement.

Ana Barac, MD, PHD, chair of cardio-oncology at Inova Schar Cancer Institute and Inova Heart and Vascular Institute, Fairfax, Va., who wasn’t involved in the study, agreed.

“The most important message is to look at preexisting cardiovascular disease, oncology diagnosis, and be aware of existing disparities in a specific cancer and CVD,” Barac said in an interview.

“What should NOT happen is to overinterpret this report of cardiotoxicity as an indication to modify/avoid planned cancer treatment to decrease cardiotoxicity. This approach could worsen oncology outcomes and lead to undertreatment of cancer, therefore posing real danger,” said Dr. Barac.

The study was presented at the American College of Cardiology Advancing the Cardiovascular Care of the Oncology Patient 2023 conference.
 

Causes unclear

Chemotherapy is known to increase the risk of cardiovascular heart failure and other forms of CVD, but less is known about racial disparities in the incidence of chemotherapy-induced cardiotoxicity.

Mr. Gebeyehu and colleagues conducted a systematic review and meta-analysis of the available literature to assess racial disparities in CV adverse effects among cancer patients who were treated with chemotherapeutic agents. They screened 7,057 studies, fully reviewed 57, and included 24 studies, representing 683,749 participants, in their analysis.

Breast cancer was the most commonly reported malignancy. Other common malignancies were prostate, kidney, and hematologic malignancies such as leukemia and lymphoma.

Chemotherapeutic agents included anthracyclines (doxorubicin, daunorubicin), trastuzumab, and hormonal therapies.

Black race or African ancestry was associated with increased odds of chemotherapy-associated cardiotoxicity (odds ratio, 1.71; 95% confidence interval, 1.40-2.10), as well as congestive heart failure (OR, 1.92; 95% CI, 1.68-2.19).

Mr. Gebeyehu said in an interview that it’s hard to speculate on causation with an analysis of preexisting data such as this. “Our initial analysis that we’ve reported on so far are unadjusted values, meaning they don’t adjust for those potential underlying factors,” he noted.

“However, some of the studies individually controlled for socioeconomic factors and still found increased vulnerability to chemotherapy-associated cardiotoxicity in patients of Black race or African ancestry,” Mr. Gebeyehu said.

“It’s certainly possible that a mix of both biological and socioeconomic factors are interacting to lead to these disparities. One example could be the underrepresentation of Black patients in clinical trials to develop drugs. These could lead to chemotherapeutic agents being poorly optimized in this population relative to other racial/ethnic groups,” he added.

Dr. Barac said this study adds to the growing body of evidence about the importance of racial disparities in CVD and cancer outcomes.

“It is important to note that only the unadjusted odds ratio was reported and that much more detail is needed to understand what may be underlying the disparities. It is critically important to await the adjusted analysis, as well as details of the type of cancers and treatment used, before clinical implications can be discussed,” said Dr. Barac, who served as codirector of the conference.

“The risk of cardiotoxicity needs to be presented in the context of the oncology and CV disease burden, as both can influence the risk, and there could be a synergistic effect of disparities,” Dr. Barac added.

The study had no specific funding. Mr. Gebeyehu and Dr. Barac disclosed no relevant conflicts of interest.

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

Black patients with cancer are significantly more likely to experience cardiotoxicity and heart failure related to chemotherapy than White cancer patients are, a research review indicates.

“It’s important that both patients and clinicians be aware of these disparities so that more meaningful conversations around long-term cardiac health and cancer treatment can take place,” lead investigator Wondewossen Gebeyehu, with the University of Toronto, said in an interview.

However, patients “should not avoid chemotherapy, as the most important thing is making sure they get the best cancer treatment possible, and studies already show Black patients may get less optimal cancer treatments,” Mr. Gebeyehu added in a statement.

Ana Barac, MD, PHD, chair of cardio-oncology at Inova Schar Cancer Institute and Inova Heart and Vascular Institute, Fairfax, Va., who wasn’t involved in the study, agreed.

“The most important message is to look at preexisting cardiovascular disease, oncology diagnosis, and be aware of existing disparities in a specific cancer and CVD,” Barac said in an interview.

“What should NOT happen is to overinterpret this report of cardiotoxicity as an indication to modify/avoid planned cancer treatment to decrease cardiotoxicity. This approach could worsen oncology outcomes and lead to undertreatment of cancer, therefore posing real danger,” said Dr. Barac.

The study was presented at the American College of Cardiology Advancing the Cardiovascular Care of the Oncology Patient 2023 conference.
 

Causes unclear

Chemotherapy is known to increase the risk of cardiovascular heart failure and other forms of CVD, but less is known about racial disparities in the incidence of chemotherapy-induced cardiotoxicity.

Mr. Gebeyehu and colleagues conducted a systematic review and meta-analysis of the available literature to assess racial disparities in CV adverse effects among cancer patients who were treated with chemotherapeutic agents. They screened 7,057 studies, fully reviewed 57, and included 24 studies, representing 683,749 participants, in their analysis.

Breast cancer was the most commonly reported malignancy. Other common malignancies were prostate, kidney, and hematologic malignancies such as leukemia and lymphoma.

Chemotherapeutic agents included anthracyclines (doxorubicin, daunorubicin), trastuzumab, and hormonal therapies.

Black race or African ancestry was associated with increased odds of chemotherapy-associated cardiotoxicity (odds ratio, 1.71; 95% confidence interval, 1.40-2.10), as well as congestive heart failure (OR, 1.92; 95% CI, 1.68-2.19).

Mr. Gebeyehu said in an interview that it’s hard to speculate on causation with an analysis of preexisting data such as this. “Our initial analysis that we’ve reported on so far are unadjusted values, meaning they don’t adjust for those potential underlying factors,” he noted.

“However, some of the studies individually controlled for socioeconomic factors and still found increased vulnerability to chemotherapy-associated cardiotoxicity in patients of Black race or African ancestry,” Mr. Gebeyehu said.

“It’s certainly possible that a mix of both biological and socioeconomic factors are interacting to lead to these disparities. One example could be the underrepresentation of Black patients in clinical trials to develop drugs. These could lead to chemotherapeutic agents being poorly optimized in this population relative to other racial/ethnic groups,” he added.

Dr. Barac said this study adds to the growing body of evidence about the importance of racial disparities in CVD and cancer outcomes.

“It is important to note that only the unadjusted odds ratio was reported and that much more detail is needed to understand what may be underlying the disparities. It is critically important to await the adjusted analysis, as well as details of the type of cancers and treatment used, before clinical implications can be discussed,” said Dr. Barac, who served as codirector of the conference.

“The risk of cardiotoxicity needs to be presented in the context of the oncology and CV disease burden, as both can influence the risk, and there could be a synergistic effect of disparities,” Dr. Barac added.

The study had no specific funding. Mr. Gebeyehu and Dr. Barac disclosed no relevant conflicts of interest.

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

Non-Hispanic persons of African ancestry typically have worse clinical outcomes from colorectal cancer (CRC) than individuals of other heritages, a disparity attributed to many factors, including socioeconomic, environmental, and genetic influences, as well as less access to care.

Results from a new genomic study provide greater clarity regarding the genetic piece of the puzzle: Persons of African background tend to have fewer targetable alterations, compared with patients of other races.

The findings were presented in a briefing and scientific poster session at the annual meeting of the American Association for Cancer Research.

Overall, the numbers to date show a clear trend: The incidence of and mortality from CRC are higher among Black patients than other populations. However, the extent to which genetic difference plays a role in these disparities remains unclear.

In the current study, researchers from Memorial Sloan Kettering (MSK) Cancer Center in New York explored how germline and somatic genomic alterations differ among patients of African ancestry, in comparison with those of European and other heritage, and how those differences might influence CRC outcomes.

Lead author Henry Walch, MS, a computational biologist at MSK, and colleagues compared genomic profiles among nearly 3,800 patients with CRC who were treated at MSK from 2014 to 2022. Patients in the study were classified by genetic ancestry as European (3,201 patients), African (236 patients), East Asian (253 patients), and South Asian (89 patients).

Tumor and normal tissues from the patients underwent next-generation DNA sequencing with a panel that covers 505 cancer-associated genes.

An analysis of overall survival by genetic ancestry confirmed findings from other studies: Overall survival was significantly worse among patients of African ancestry than among those of other groups (median 45.7 vs. 67.1 months).

The investigators used a precision oncology knowledge base (OncoKB) to assign levels of therapeutic actionability for each genomic alteration that was identified. The highest assigned value was for drugs that have been approved by the U.S. Food and Drug Administration and that target FDA-recognized biomarkers. The lowest value was assigned to biomarkers for which there was “compelling biological evidence” that the particular biomarker predicted response to a drug.

The team found that the percentage of patients who qualified for immunotherapy on the basis of microsatellite instability or high tumor mutational burden was significantly lower among patients of African heritage, compared with those of European heritage (13.5% vs. 20.4%; P = .008).

Compared with those of European ancestry, patients of African ancestry had significantly fewer actionable alterations (5.6% vs. 11.2%; P = .01). This difference was largely driven by the lack of targetable BRAF mutations (1.8% vs. 5.0%).

Mutations in APC, the most frequently altered gene in CRC, are typically associated with cancer outcomes, but the authors found that overall survival was similar for patients of African heritage regardless of whether they had altered or wild-type APC (median overall survival, 45.0 months for altered APC vs. 45.9 months for wild-type APC; P = .91). However, a significant association between APC status and overall survival was observed for patients of European ancestry (median, 64.6 months for altered APC vs. 45.6 months for wild-type APC; P < .0001).

Analyses that accounted for sex, age, primary tumor location, and stage at diagnosis also showed an association between APC status and overall survival for patients of European heritage (hazard ratio, 0.64), but not for patients of African heritage (HR, 0.74, P = .492).

Mr. Walch noted that a limitation of the study is that information regarding comprehensive treatment, environmental exposures, lifestyle, and socioeconomic factors was not available for the analysis but that these elements likely play an important role in patient outcomes.

“This is a complex problem involving many unseen factors, and the genomic landscape is a piece of a much larger puzzle,” said Mr. Walch. He noted that future studies will incorporate these factors into the models “with the ultimate goal of identifying opportunities to intervene and improve outcomes.”

Briefing moderator Lisa Newman, MD, MPH, of Weill Cornell Medicine and New York–Presbyterian, in New York, commented that Mr. Walch presented “some very compelling data that demonstrate the importance of including individuals from diverse backgrounds into [cancer] research.”

The study was funded in part by a Chris4Life Early Career Investigator Award Grant from the Colorectal Cancer Alliance for Francisco Sanchez-Vega, PhD, senior author of the study. Dr. Sanchez-Vega was also supported by an AACR-Minority and Minority-serving Institution Faculty Scholar in Cancer Research Award. Mr. Walch and Dr. Newman have disclosed no relevant financial relationships.

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

Non-Hispanic persons of African ancestry typically have worse clinical outcomes from colorectal cancer (CRC) than individuals of other heritages, a disparity attributed to many factors, including socioeconomic, environmental, and genetic influences, as well as less access to care.

Results from a new genomic study provide greater clarity regarding the genetic piece of the puzzle: Persons of African background tend to have fewer targetable alterations, compared with patients of other races.

The findings were presented in a briefing and scientific poster session at the annual meeting of the American Association for Cancer Research.

Overall, the numbers to date show a clear trend: The incidence of and mortality from CRC are higher among Black patients than other populations. However, the extent to which genetic difference plays a role in these disparities remains unclear.

In the current study, researchers from Memorial Sloan Kettering (MSK) Cancer Center in New York explored how germline and somatic genomic alterations differ among patients of African ancestry, in comparison with those of European and other heritage, and how those differences might influence CRC outcomes.

Lead author Henry Walch, MS, a computational biologist at MSK, and colleagues compared genomic profiles among nearly 3,800 patients with CRC who were treated at MSK from 2014 to 2022. Patients in the study were classified by genetic ancestry as European (3,201 patients), African (236 patients), East Asian (253 patients), and South Asian (89 patients).

Tumor and normal tissues from the patients underwent next-generation DNA sequencing with a panel that covers 505 cancer-associated genes.

An analysis of overall survival by genetic ancestry confirmed findings from other studies: Overall survival was significantly worse among patients of African ancestry than among those of other groups (median 45.7 vs. 67.1 months).

The investigators used a precision oncology knowledge base (OncoKB) to assign levels of therapeutic actionability for each genomic alteration that was identified. The highest assigned value was for drugs that have been approved by the U.S. Food and Drug Administration and that target FDA-recognized biomarkers. The lowest value was assigned to biomarkers for which there was “compelling biological evidence” that the particular biomarker predicted response to a drug.

The team found that the percentage of patients who qualified for immunotherapy on the basis of microsatellite instability or high tumor mutational burden was significantly lower among patients of African heritage, compared with those of European heritage (13.5% vs. 20.4%; P = .008).

Compared with those of European ancestry, patients of African ancestry had significantly fewer actionable alterations (5.6% vs. 11.2%; P = .01). This difference was largely driven by the lack of targetable BRAF mutations (1.8% vs. 5.0%).

Mutations in APC, the most frequently altered gene in CRC, are typically associated with cancer outcomes, but the authors found that overall survival was similar for patients of African heritage regardless of whether they had altered or wild-type APC (median overall survival, 45.0 months for altered APC vs. 45.9 months for wild-type APC; P = .91). However, a significant association between APC status and overall survival was observed for patients of European ancestry (median, 64.6 months for altered APC vs. 45.6 months for wild-type APC; P < .0001).

Analyses that accounted for sex, age, primary tumor location, and stage at diagnosis also showed an association between APC status and overall survival for patients of European heritage (hazard ratio, 0.64), but not for patients of African heritage (HR, 0.74, P = .492).

Mr. Walch noted that a limitation of the study is that information regarding comprehensive treatment, environmental exposures, lifestyle, and socioeconomic factors was not available for the analysis but that these elements likely play an important role in patient outcomes.

“This is a complex problem involving many unseen factors, and the genomic landscape is a piece of a much larger puzzle,” said Mr. Walch. He noted that future studies will incorporate these factors into the models “with the ultimate goal of identifying opportunities to intervene and improve outcomes.”

Briefing moderator Lisa Newman, MD, MPH, of Weill Cornell Medicine and New York–Presbyterian, in New York, commented that Mr. Walch presented “some very compelling data that demonstrate the importance of including individuals from diverse backgrounds into [cancer] research.”

The study was funded in part by a Chris4Life Early Career Investigator Award Grant from the Colorectal Cancer Alliance for Francisco Sanchez-Vega, PhD, senior author of the study. Dr. Sanchez-Vega was also supported by an AACR-Minority and Minority-serving Institution Faculty Scholar in Cancer Research Award. Mr. Walch and Dr. Newman have disclosed no relevant financial relationships.

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

Non-Hispanic persons of African ancestry typically have worse clinical outcomes from colorectal cancer (CRC) than individuals of other heritages, a disparity attributed to many factors, including socioeconomic, environmental, and genetic influences, as well as less access to care.

Results from a new genomic study provide greater clarity regarding the genetic piece of the puzzle: Persons of African background tend to have fewer targetable alterations, compared with patients of other races.

The findings were presented in a briefing and scientific poster session at the annual meeting of the American Association for Cancer Research.

Overall, the numbers to date show a clear trend: The incidence of and mortality from CRC are higher among Black patients than other populations. However, the extent to which genetic difference plays a role in these disparities remains unclear.

In the current study, researchers from Memorial Sloan Kettering (MSK) Cancer Center in New York explored how germline and somatic genomic alterations differ among patients of African ancestry, in comparison with those of European and other heritage, and how those differences might influence CRC outcomes.

Lead author Henry Walch, MS, a computational biologist at MSK, and colleagues compared genomic profiles among nearly 3,800 patients with CRC who were treated at MSK from 2014 to 2022. Patients in the study were classified by genetic ancestry as European (3,201 patients), African (236 patients), East Asian (253 patients), and South Asian (89 patients).

Tumor and normal tissues from the patients underwent next-generation DNA sequencing with a panel that covers 505 cancer-associated genes.

An analysis of overall survival by genetic ancestry confirmed findings from other studies: Overall survival was significantly worse among patients of African ancestry than among those of other groups (median 45.7 vs. 67.1 months).

The investigators used a precision oncology knowledge base (OncoKB) to assign levels of therapeutic actionability for each genomic alteration that was identified. The highest assigned value was for drugs that have been approved by the U.S. Food and Drug Administration and that target FDA-recognized biomarkers. The lowest value was assigned to biomarkers for which there was “compelling biological evidence” that the particular biomarker predicted response to a drug.

The team found that the percentage of patients who qualified for immunotherapy on the basis of microsatellite instability or high tumor mutational burden was significantly lower among patients of African heritage, compared with those of European heritage (13.5% vs. 20.4%; P = .008).

Compared with those of European ancestry, patients of African ancestry had significantly fewer actionable alterations (5.6% vs. 11.2%; P = .01). This difference was largely driven by the lack of targetable BRAF mutations (1.8% vs. 5.0%).

Mutations in APC, the most frequently altered gene in CRC, are typically associated with cancer outcomes, but the authors found that overall survival was similar for patients of African heritage regardless of whether they had altered or wild-type APC (median overall survival, 45.0 months for altered APC vs. 45.9 months for wild-type APC; P = .91). However, a significant association between APC status and overall survival was observed for patients of European ancestry (median, 64.6 months for altered APC vs. 45.6 months for wild-type APC; P < .0001).

Analyses that accounted for sex, age, primary tumor location, and stage at diagnosis also showed an association between APC status and overall survival for patients of European heritage (hazard ratio, 0.64), but not for patients of African heritage (HR, 0.74, P = .492).

Mr. Walch noted that a limitation of the study is that information regarding comprehensive treatment, environmental exposures, lifestyle, and socioeconomic factors was not available for the analysis but that these elements likely play an important role in patient outcomes.

“This is a complex problem involving many unseen factors, and the genomic landscape is a piece of a much larger puzzle,” said Mr. Walch. He noted that future studies will incorporate these factors into the models “with the ultimate goal of identifying opportunities to intervene and improve outcomes.”

Briefing moderator Lisa Newman, MD, MPH, of Weill Cornell Medicine and New York–Presbyterian, in New York, commented that Mr. Walch presented “some very compelling data that demonstrate the importance of including individuals from diverse backgrounds into [cancer] research.”

The study was funded in part by a Chris4Life Early Career Investigator Award Grant from the Colorectal Cancer Alliance for Francisco Sanchez-Vega, PhD, senior author of the study. Dr. Sanchez-Vega was also supported by an AACR-Minority and Minority-serving Institution Faculty Scholar in Cancer Research Award. Mr. Walch and Dr. Newman have disclosed no relevant financial relationships.

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

FROM AACR 2023

Systemic therapy prior to surgery has been slow to catch on in the treatment of patients with resectable non–small cell lung cancer (NSCLC), primarily out of concern that neoadjuvant therapy could delay surgery or render patients ineligible for resection.

That may change, however, in light of new data from the phase 3 AEGEAN trial.

AEGEAN showed that neoadjuvant immunotherapy with durvalumab (Imfinzi) and chemotherapy followed by adjuvant durvalumab was associated with significant improvements in pathologic complete response rates and event-free survival, compared with neoadjuvant placebo plus chemotherapy followed by adjuvant placebo, and it did not affect patients’ ability to undergo surgery.

The event-free survival benefit among patients who received durvalumab translated to a 32% reduction in the risk of recurrence, recurrence precluding definitive surgery, or death, John V. Heymach, MD, reported in an oral abstract session at the annual meeting of the American Association for Cancer Research.

“Perioperative durvalumab plus neoadjuvant chemotherapy is a potential new treatment for patients with resectable non–small cell lung cancer,” said Dr. Heymach, chair of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

The AEGEAN findings confirm the benefits of neoadjuvant immunotherapy that were first seen on a large scale in the Checkmate 816 study, which was reported at last year’s AACR annual meeting.

In Checkmate 816, adding the immune checkpoint inhibitor nivolumab to chemotherapy in the neoadjuvant setting resulted in significantly longer event-free survival and a 14-fold greater likelihood of a pathologic complete response compared with chemotherapy alone.

“I’m impressed by the fact that we now have a second study that shows the benefits of immunotherapy in the neoadjuvant setting, along with several adjuvant studies,” the invited discussant, Roy S. Herbst, MD, PhD, deputy director of the Yale Cancer Center, New Haven, Conn., said in an interview. “There’s no doubt that in early lung cancer, resectable disease, immunotherapy is part of the equation.”

For the current study, Dr. Heymach and colleagues recruited 802 patients from 222 sites in North and South America, Europe, and Asia. The patients had NSCLC and were treatment-naive, regardless of programmed cell death–ligand-1 (PD-L1) expression.

After excluding patients with targetable EGFR/ALK alterations, the team randomly allocated 740 patients who had good performance status (ECOG 0 or 1) to receive either neoadjuvant chemoimmunotherapy plus adjuvant immunotherapy or neoadjuvant chemotherapy alone. Overall, 77.6% of patients in the treatment arm and 76.7% of patients in the placebo arm underwent surgery following neoadjuvant therapy.

At the trial’s first planned interim analysis, for patients assigned to preoperative durvalumab plus platinum-based chemotherapy and postoperative durvalumab, the 12-month event-free survival rate was 73.4%, compared with 64.5% for patients who received chemotherapy alone before and placebo after surgery (stratified P = .003902).

The other endpoint, pathologic complete response, was observed in 17.2% of patients in the durvalumab arm, vs. 4.3% in the control arm – a 13% difference (P = .000036). Major pathologic responses, a secondary efficacy endpoint, were seen in 33.3% and 12.3% of patients, respectively.

The benefits of durvalumab were consistent across all subgroups, including those based on age at randomization, sex, performance status, race, smoking, histology (squamous vs. nonsquamous), disease stage, baseline PD-L1 expression, and planned neoadjuvant agent.

The safety profile of durvalumab plus chemotherapy was manageable, and the addition of durvalumab did not affect patients’ ability to complete four cycles of neoadjuvant chemotherapy, Dr. Heymach said.

Are these data practice changing?

Dr. Herbst gave a “resounding ‘Yes.’ “

But while the AEGEAN protocol represents a new standard of care, it can’t yet be labeled the standard of care, Dr. Herbst explained.

Dr. Herbst emphasized that, because this regimen was not compared against the current standard of care, it’s “impossible to determine” whether this is indeed the new standard.

“The data are early, and additional maturity is needed to better understand the benefit of the extra adjuvant therapy, and we’ll await the survival results,” he said.

It will also be important to analyze why some patients have only minor responses with the addition of durvalumab and whether there are resistance mechanisms at play for these patients. That would be a great setting “to start to test new therapies in a personalized way,” Dr. Herbst said.

Dr. Heymach and Dr. Herbst disclosed ties to AstraZeneca, which funded the study.
 

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

FROM AACR 2023

Systemic therapy prior to surgery has been slow to catch on in the treatment of patients with resectable non–small cell lung cancer (NSCLC), primarily out of concern that neoadjuvant therapy could delay surgery or render patients ineligible for resection.

That may change, however, in light of new data from the phase 3 AEGEAN trial.

AEGEAN showed that neoadjuvant immunotherapy with durvalumab (Imfinzi) and chemotherapy followed by adjuvant durvalumab was associated with significant improvements in pathologic complete response rates and event-free survival, compared with neoadjuvant placebo plus chemotherapy followed by adjuvant placebo, and it did not affect patients’ ability to undergo surgery.

The event-free survival benefit among patients who received durvalumab translated to a 32% reduction in the risk of recurrence, recurrence precluding definitive surgery, or death, John V. Heymach, MD, reported in an oral abstract session at the annual meeting of the American Association for Cancer Research.

“Perioperative durvalumab plus neoadjuvant chemotherapy is a potential new treatment for patients with resectable non–small cell lung cancer,” said Dr. Heymach, chair of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

The AEGEAN findings confirm the benefits of neoadjuvant immunotherapy that were first seen on a large scale in the Checkmate 816 study, which was reported at last year’s AACR annual meeting.

In Checkmate 816, adding the immune checkpoint inhibitor nivolumab to chemotherapy in the neoadjuvant setting resulted in significantly longer event-free survival and a 14-fold greater likelihood of a pathologic complete response compared with chemotherapy alone.

“I’m impressed by the fact that we now have a second study that shows the benefits of immunotherapy in the neoadjuvant setting, along with several adjuvant studies,” the invited discussant, Roy S. Herbst, MD, PhD, deputy director of the Yale Cancer Center, New Haven, Conn., said in an interview. “There’s no doubt that in early lung cancer, resectable disease, immunotherapy is part of the equation.”

For the current study, Dr. Heymach and colleagues recruited 802 patients from 222 sites in North and South America, Europe, and Asia. The patients had NSCLC and were treatment-naive, regardless of programmed cell death–ligand-1 (PD-L1) expression.

After excluding patients with targetable EGFR/ALK alterations, the team randomly allocated 740 patients who had good performance status (ECOG 0 or 1) to receive either neoadjuvant chemoimmunotherapy plus adjuvant immunotherapy or neoadjuvant chemotherapy alone. Overall, 77.6% of patients in the treatment arm and 76.7% of patients in the placebo arm underwent surgery following neoadjuvant therapy.

At the trial’s first planned interim analysis, for patients assigned to preoperative durvalumab plus platinum-based chemotherapy and postoperative durvalumab, the 12-month event-free survival rate was 73.4%, compared with 64.5% for patients who received chemotherapy alone before and placebo after surgery (stratified P = .003902).

The other endpoint, pathologic complete response, was observed in 17.2% of patients in the durvalumab arm, vs. 4.3% in the control arm – a 13% difference (P = .000036). Major pathologic responses, a secondary efficacy endpoint, were seen in 33.3% and 12.3% of patients, respectively.

The benefits of durvalumab were consistent across all subgroups, including those based on age at randomization, sex, performance status, race, smoking, histology (squamous vs. nonsquamous), disease stage, baseline PD-L1 expression, and planned neoadjuvant agent.

The safety profile of durvalumab plus chemotherapy was manageable, and the addition of durvalumab did not affect patients’ ability to complete four cycles of neoadjuvant chemotherapy, Dr. Heymach said.

Are these data practice changing?

Dr. Herbst gave a “resounding ‘Yes.’ “

But while the AEGEAN protocol represents a new standard of care, it can’t yet be labeled the standard of care, Dr. Herbst explained.

Dr. Herbst emphasized that, because this regimen was not compared against the current standard of care, it’s “impossible to determine” whether this is indeed the new standard.

“The data are early, and additional maturity is needed to better understand the benefit of the extra adjuvant therapy, and we’ll await the survival results,” he said.

It will also be important to analyze why some patients have only minor responses with the addition of durvalumab and whether there are resistance mechanisms at play for these patients. That would be a great setting “to start to test new therapies in a personalized way,” Dr. Herbst said.

Dr. Heymach and Dr. Herbst disclosed ties to AstraZeneca, which funded the study.
 

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

FROM AACR 2023

Systemic therapy prior to surgery has been slow to catch on in the treatment of patients with resectable non–small cell lung cancer (NSCLC), primarily out of concern that neoadjuvant therapy could delay surgery or render patients ineligible for resection.

That may change, however, in light of new data from the phase 3 AEGEAN trial.

AEGEAN showed that neoadjuvant immunotherapy with durvalumab (Imfinzi) and chemotherapy followed by adjuvant durvalumab was associated with significant improvements in pathologic complete response rates and event-free survival, compared with neoadjuvant placebo plus chemotherapy followed by adjuvant placebo, and it did not affect patients’ ability to undergo surgery.

The event-free survival benefit among patients who received durvalumab translated to a 32% reduction in the risk of recurrence, recurrence precluding definitive surgery, or death, John V. Heymach, MD, reported in an oral abstract session at the annual meeting of the American Association for Cancer Research.

“Perioperative durvalumab plus neoadjuvant chemotherapy is a potential new treatment for patients with resectable non–small cell lung cancer,” said Dr. Heymach, chair of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

The AEGEAN findings confirm the benefits of neoadjuvant immunotherapy that were first seen on a large scale in the Checkmate 816 study, which was reported at last year’s AACR annual meeting.

In Checkmate 816, adding the immune checkpoint inhibitor nivolumab to chemotherapy in the neoadjuvant setting resulted in significantly longer event-free survival and a 14-fold greater likelihood of a pathologic complete response compared with chemotherapy alone.

“I’m impressed by the fact that we now have a second study that shows the benefits of immunotherapy in the neoadjuvant setting, along with several adjuvant studies,” the invited discussant, Roy S. Herbst, MD, PhD, deputy director of the Yale Cancer Center, New Haven, Conn., said in an interview. “There’s no doubt that in early lung cancer, resectable disease, immunotherapy is part of the equation.”

For the current study, Dr. Heymach and colleagues recruited 802 patients from 222 sites in North and South America, Europe, and Asia. The patients had NSCLC and were treatment-naive, regardless of programmed cell death–ligand-1 (PD-L1) expression.

After excluding patients with targetable EGFR/ALK alterations, the team randomly allocated 740 patients who had good performance status (ECOG 0 or 1) to receive either neoadjuvant chemoimmunotherapy plus adjuvant immunotherapy or neoadjuvant chemotherapy alone. Overall, 77.6% of patients in the treatment arm and 76.7% of patients in the placebo arm underwent surgery following neoadjuvant therapy.

At the trial’s first planned interim analysis, for patients assigned to preoperative durvalumab plus platinum-based chemotherapy and postoperative durvalumab, the 12-month event-free survival rate was 73.4%, compared with 64.5% for patients who received chemotherapy alone before and placebo after surgery (stratified P = .003902).

The other endpoint, pathologic complete response, was observed in 17.2% of patients in the durvalumab arm, vs. 4.3% in the control arm – a 13% difference (P = .000036). Major pathologic responses, a secondary efficacy endpoint, were seen in 33.3% and 12.3% of patients, respectively.

The benefits of durvalumab were consistent across all subgroups, including those based on age at randomization, sex, performance status, race, smoking, histology (squamous vs. nonsquamous), disease stage, baseline PD-L1 expression, and planned neoadjuvant agent.

The safety profile of durvalumab plus chemotherapy was manageable, and the addition of durvalumab did not affect patients’ ability to complete four cycles of neoadjuvant chemotherapy, Dr. Heymach said.

Are these data practice changing?

Dr. Herbst gave a “resounding ‘Yes.’ “

But while the AEGEAN protocol represents a new standard of care, it can’t yet be labeled the standard of care, Dr. Herbst explained.

Dr. Herbst emphasized that, because this regimen was not compared against the current standard of care, it’s “impossible to determine” whether this is indeed the new standard.

“The data are early, and additional maturity is needed to better understand the benefit of the extra adjuvant therapy, and we’ll await the survival results,” he said.

It will also be important to analyze why some patients have only minor responses with the addition of durvalumab and whether there are resistance mechanisms at play for these patients. That would be a great setting “to start to test new therapies in a personalized way,” Dr. Herbst said.

Dr. Heymach and Dr. Herbst disclosed ties to AstraZeneca, which funded the study.
 

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

WASHINGTON – A group therapy suicide prevention program for veterans delivered via telehealth is feasible and acceptable, new research shows.

Skeptics had worried that participating in the program through telehealth would exacerbate safety and other issues veterans had about discussing suicide in a group setting, study investigator Sarah Sullivan, PhD student, Health Psychology & Clinical Science, City University of New York, told this news organization.

“But that for us was not really true. People opened up about their suicidal thoughts and triggers even on this telehealth format, and that’s really important for providers to know,” she said.

The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
 

Trial run

Suicide is a major public health issue, particularly for veterans. Recent data from the Veterans Administration show 17 veterans die by suicide every day.

The current study included 15 male and 2 female veterans (29.4% White, 70.6% Hispanic) from New York City and Philadelphia. Participants had an average age of 50 and all were either deemed by a clinician to be at extremely high risk for suicide or were hospitalized for this reason.

The individuals completed an online version of the Project Life Force (PLF) program, which uses dialectical behavioral therapy and psychoeducational approaches. The program includes the brief Safety Planning intervention (SPI), aimed at reducing short-term suicide risk.

Considered a best practice, the SPI includes a written list of personal suicide warning signs or triggers, internal coping strategies, social contacts who offer support and distraction from suicidal thoughts, contact information for professionals, a suicide crisis hotline, and nearby emergency services.

In addition to these steps, the PLF program focuses on sleep, exercise, and making the safety plan accessible.

The telehealth platform for the program was WebEx software. Participants were offered a “trial run” to orient them to the technology, said Ms. Sullivan.

Group sessions were held once weekly for 10 weeks, with optional “booster” sessions if needed. Each session included about five participants.

To ensure privacy, participants were provided with headphones and laptops. This was especially important for those sharing a living space, including spouses and children, said Ms. Sullivan.
 

High ratings

Participants completed the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM). Each of these yields scores from four items rated on a Likert scale of 1-5, for a total score ranging from 5 to 20, with higher scores indicating higher ratings.

Veterans rated PLF-T as highly acceptable (mean AIM, 17.50), appropriate (mean IAM, 17.25), and feasible (mean FIM, 18).

Study participants reported the program was convenient and noted that it decreased the burden of traveling to sessions, especially during the COVID-19 pandemic.

They also reported the program was less likely to compete with other demands such as childcare and other appointments, said Ms. Sullivan.

In addition, it helped those with comorbidities such as posttraumatic stress disorder, she added. She noted veterans with PTSD may be triggered on subways or buses when traveling to in-person treatment sessions.

“That can take away from addressing the suicidal triggers,” said Ms. Sullivan. “So, this program allows them to fully concentrate on the safety plan.”

Results showed that study participants “enjoyed the group and would recommend it to others,” said Ms. Sullivan. “I think that signifies the group was effective in its goal of mitigating loneliness, which was exacerbated during the COVID-19 pandemic, and creating a socially supportive environment, especially for the vets living alone.”

Veterans also reported that the program helped them understand the connection between depression or PTSD and suicidal thoughts, urges, and plans. In addition, they appreciated the group dynamics, where they felt connected to other veterans experiencing similar challenges.
 

Hopeful results

Commenting on the study, Paul E. Holtzheimer, MD, deputy director for research at the National Center for PTSD, praised the study for focusing on a very high-risk group.

“This gets you closer to the population you’re probably going to have an impact on in terms of preventing suicide,” said Dr. Holtzheimer, a  professor of psychiatry and surgery at Dartmouth College’s Geisel School of Medicine, Hanover, N.H.

The fact that many of the participants had attempted suicide in the last year underlines that this was a very high-risk population, said Dr. Holtzheimer. “Not only are they thinking about suicide, but almost two-thirds had actually attempted or tried something.”

This kind of program “would be great for rural environments where people may be living like four hours away from the VA or a clinic,” said Dr. Holtzheimer, noting that many veterans are often quite isolated.

“One of the very positive outcomes of the COVID-19 pandemic was helping us strengthen our ability to do telehealth,” he said.

However, Dr. Holtzheimer noted the study was small and qualitative. “The next step ideally would be a controlled trial looking at not just ideation but at risky behavior or clear suicide attempts or preparation, like buying a gun or hoarding medication, to help determine efficacy.”

The researchers and Dr. Holtzheimer report no relevant financial relationships.

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

WASHINGTON – A group therapy suicide prevention program for veterans delivered via telehealth is feasible and acceptable, new research shows.

Skeptics had worried that participating in the program through telehealth would exacerbate safety and other issues veterans had about discussing suicide in a group setting, study investigator Sarah Sullivan, PhD student, Health Psychology & Clinical Science, City University of New York, told this news organization.

“But that for us was not really true. People opened up about their suicidal thoughts and triggers even on this telehealth format, and that’s really important for providers to know,” she said.

The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
 

Trial run

Suicide is a major public health issue, particularly for veterans. Recent data from the Veterans Administration show 17 veterans die by suicide every day.

The current study included 15 male and 2 female veterans (29.4% White, 70.6% Hispanic) from New York City and Philadelphia. Participants had an average age of 50 and all were either deemed by a clinician to be at extremely high risk for suicide or were hospitalized for this reason.

The individuals completed an online version of the Project Life Force (PLF) program, which uses dialectical behavioral therapy and psychoeducational approaches. The program includes the brief Safety Planning intervention (SPI), aimed at reducing short-term suicide risk.

Considered a best practice, the SPI includes a written list of personal suicide warning signs or triggers, internal coping strategies, social contacts who offer support and distraction from suicidal thoughts, contact information for professionals, a suicide crisis hotline, and nearby emergency services.

In addition to these steps, the PLF program focuses on sleep, exercise, and making the safety plan accessible.

The telehealth platform for the program was WebEx software. Participants were offered a “trial run” to orient them to the technology, said Ms. Sullivan.

Group sessions were held once weekly for 10 weeks, with optional “booster” sessions if needed. Each session included about five participants.

To ensure privacy, participants were provided with headphones and laptops. This was especially important for those sharing a living space, including spouses and children, said Ms. Sullivan.
 

High ratings

Participants completed the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM). Each of these yields scores from four items rated on a Likert scale of 1-5, for a total score ranging from 5 to 20, with higher scores indicating higher ratings.

Veterans rated PLF-T as highly acceptable (mean AIM, 17.50), appropriate (mean IAM, 17.25), and feasible (mean FIM, 18).

Study participants reported the program was convenient and noted that it decreased the burden of traveling to sessions, especially during the COVID-19 pandemic.

They also reported the program was less likely to compete with other demands such as childcare and other appointments, said Ms. Sullivan.

In addition, it helped those with comorbidities such as posttraumatic stress disorder, she added. She noted veterans with PTSD may be triggered on subways or buses when traveling to in-person treatment sessions.

“That can take away from addressing the suicidal triggers,” said Ms. Sullivan. “So, this program allows them to fully concentrate on the safety plan.”

Results showed that study participants “enjoyed the group and would recommend it to others,” said Ms. Sullivan. “I think that signifies the group was effective in its goal of mitigating loneliness, which was exacerbated during the COVID-19 pandemic, and creating a socially supportive environment, especially for the vets living alone.”

Veterans also reported that the program helped them understand the connection between depression or PTSD and suicidal thoughts, urges, and plans. In addition, they appreciated the group dynamics, where they felt connected to other veterans experiencing similar challenges.
 

Hopeful results

Commenting on the study, Paul E. Holtzheimer, MD, deputy director for research at the National Center for PTSD, praised the study for focusing on a very high-risk group.

“This gets you closer to the population you’re probably going to have an impact on in terms of preventing suicide,” said Dr. Holtzheimer, a  professor of psychiatry and surgery at Dartmouth College’s Geisel School of Medicine, Hanover, N.H.

The fact that many of the participants had attempted suicide in the last year underlines that this was a very high-risk population, said Dr. Holtzheimer. “Not only are they thinking about suicide, but almost two-thirds had actually attempted or tried something.”

This kind of program “would be great for rural environments where people may be living like four hours away from the VA or a clinic,” said Dr. Holtzheimer, noting that many veterans are often quite isolated.

“One of the very positive outcomes of the COVID-19 pandemic was helping us strengthen our ability to do telehealth,” he said.

However, Dr. Holtzheimer noted the study was small and qualitative. “The next step ideally would be a controlled trial looking at not just ideation but at risky behavior or clear suicide attempts or preparation, like buying a gun or hoarding medication, to help determine efficacy.”

The researchers and Dr. Holtzheimer report no relevant financial relationships.

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

WASHINGTON – A group therapy suicide prevention program for veterans delivered via telehealth is feasible and acceptable, new research shows.

Skeptics had worried that participating in the program through telehealth would exacerbate safety and other issues veterans had about discussing suicide in a group setting, study investigator Sarah Sullivan, PhD student, Health Psychology & Clinical Science, City University of New York, told this news organization.

“But that for us was not really true. People opened up about their suicidal thoughts and triggers even on this telehealth format, and that’s really important for providers to know,” she said.

The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
 

Trial run

Suicide is a major public health issue, particularly for veterans. Recent data from the Veterans Administration show 17 veterans die by suicide every day.

The current study included 15 male and 2 female veterans (29.4% White, 70.6% Hispanic) from New York City and Philadelphia. Participants had an average age of 50 and all were either deemed by a clinician to be at extremely high risk for suicide or were hospitalized for this reason.

The individuals completed an online version of the Project Life Force (PLF) program, which uses dialectical behavioral therapy and psychoeducational approaches. The program includes the brief Safety Planning intervention (SPI), aimed at reducing short-term suicide risk.

Considered a best practice, the SPI includes a written list of personal suicide warning signs or triggers, internal coping strategies, social contacts who offer support and distraction from suicidal thoughts, contact information for professionals, a suicide crisis hotline, and nearby emergency services.

In addition to these steps, the PLF program focuses on sleep, exercise, and making the safety plan accessible.

The telehealth platform for the program was WebEx software. Participants were offered a “trial run” to orient them to the technology, said Ms. Sullivan.

Group sessions were held once weekly for 10 weeks, with optional “booster” sessions if needed. Each session included about five participants.

To ensure privacy, participants were provided with headphones and laptops. This was especially important for those sharing a living space, including spouses and children, said Ms. Sullivan.
 

High ratings

Participants completed the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM). Each of these yields scores from four items rated on a Likert scale of 1-5, for a total score ranging from 5 to 20, with higher scores indicating higher ratings.

Veterans rated PLF-T as highly acceptable (mean AIM, 17.50), appropriate (mean IAM, 17.25), and feasible (mean FIM, 18).

Study participants reported the program was convenient and noted that it decreased the burden of traveling to sessions, especially during the COVID-19 pandemic.

They also reported the program was less likely to compete with other demands such as childcare and other appointments, said Ms. Sullivan.

In addition, it helped those with comorbidities such as posttraumatic stress disorder, she added. She noted veterans with PTSD may be triggered on subways or buses when traveling to in-person treatment sessions.

“That can take away from addressing the suicidal triggers,” said Ms. Sullivan. “So, this program allows them to fully concentrate on the safety plan.”

Results showed that study participants “enjoyed the group and would recommend it to others,” said Ms. Sullivan. “I think that signifies the group was effective in its goal of mitigating loneliness, which was exacerbated during the COVID-19 pandemic, and creating a socially supportive environment, especially for the vets living alone.”

Veterans also reported that the program helped them understand the connection between depression or PTSD and suicidal thoughts, urges, and plans. In addition, they appreciated the group dynamics, where they felt connected to other veterans experiencing similar challenges.
 

Hopeful results

Commenting on the study, Paul E. Holtzheimer, MD, deputy director for research at the National Center for PTSD, praised the study for focusing on a very high-risk group.

“This gets you closer to the population you’re probably going to have an impact on in terms of preventing suicide,” said Dr. Holtzheimer, a  professor of psychiatry and surgery at Dartmouth College’s Geisel School of Medicine, Hanover, N.H.

The fact that many of the participants had attempted suicide in the last year underlines that this was a very high-risk population, said Dr. Holtzheimer. “Not only are they thinking about suicide, but almost two-thirds had actually attempted or tried something.”

This kind of program “would be great for rural environments where people may be living like four hours away from the VA or a clinic,” said Dr. Holtzheimer, noting that many veterans are often quite isolated.

“One of the very positive outcomes of the COVID-19 pandemic was helping us strengthen our ability to do telehealth,” he said.

However, Dr. Holtzheimer noted the study was small and qualitative. “The next step ideally would be a controlled trial looking at not just ideation but at risky behavior or clear suicide attempts or preparation, like buying a gun or hoarding medication, to help determine efficacy.”

The researchers and Dr. Holtzheimer report no relevant financial relationships.

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