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While it’s well known that COVID-19 vaccines are less effective in patients with chronic lymphocytic leukemia (CLL) who take immunity-lowering drugs, a new study offers fresh insight into what’s happening inside the body. In these patients, the vaccines often don’t boost B cells, which produce antibodies, but they do strengthen T cells, potentially providing crucial protection against severe illness and death.

These findings don’t reveal whether the T-cell boost actually provides extra protection against COVID-19. Still, the study suggests that patients with CLL should be vaccinated no matter which medications they’re taking, coauthor and hematologist/oncologist Clemens-Martin Wendtner, MD, of the Munich (Germany) Clinic, said in an interview.

“Do not defer or pause treatment,” said Dr. Wendtner, whose study was published in Blood Advances.

Patients with CLL appear to have among the weakest responses to the COVID-19 vaccine among people with various types of blood cancer. A meta-analysis published in 2022 found that seropositivity rates following vaccination were just 51% in patients with CLL, compared with 80%-90% in those with acute leukemia and 76%-80% of those with myeloma.

“Usually, the response rate to vaccination among the nonimmunocompromised would be 95%,” Dr. Wendtner said.

Research has also suggested that patients treated with B-cell pathway inhibitors and anti-CD20 antibodies are especially likely to have poorer responses to COVID-19 vaccines, no surprise considering that their job is to dampen the immune system. But there’s an unanswered question, according to Dr. Wendtner: Does “just measuring B-cell response tell us everything about the immune response?”

The new prospective, single-institution study aims to answer that question in patients who each received two types of vaccines. Researchers compared peripheral blood mononuclear cell transcriptional response with antibody and T-cell response rates in 15 patients with CLL/small lymphocytic lymphoma following vaccination with both the Pfizer-BioNTech and AstraZeneca vaccines.

The average antibody response was limited. “Overall, 7/15 of patients failed to mount a humoral response even after three-dose vaccination,” the researchers reported. All of the patients were “heavily pretreated” with CLL medications such as venetoclax, an anti-CD20 monoclonal antibody.

By contrast, the T-cell response was much stronger: 80% of patients (12/15) had a robust response, a number that grew to 90% (14/15) after a booster. This response is “almost ideal” considering that the response in a nonimmunocompromised person would be about 99%, Dr. Wendtner said.

The study also revealed that vaccine responses were weaker in patients who took a combination of a Bruton tyrosine kinase inhibitor and venetoclax within a year.

Four patients developed COVID-19 infections with the Omicron variant about 6 months after vaccination. All had mild symptoms. A lone patient had a history of COVID-19 infection prior to vaccination.

The researchers noted that the study had several limitations, including its small size, its reliance on a single institution, and the differences in treatments and vaccination protocols among the patient population.

Broadly speaking, the study showed that “a vaccine is not in vain” in patients with CLL, “although the doctor might not detect an antibody response,” Dr. Wendtner said. He added that mixing vaccine types should provide more protection. Start with a viral vector vaccine followed by an mRNA vaccine or vice versa, he suggested.

In an interview, infectious disease physician Joshua A. Hill, MD, from Fred Hutchinson Cancer Center, Seattle, who wasn’t involved with the study, said it makes “important and interesting observations to reinforce other studies with similar findings.”

Specifically, Dr. Hill said, “despite the absence of a robust antibody response some of these patients who are on active treatment, patients can still generate robust cellular immune responses in the form of T-cell immunity. Our understanding is that having T cell immunity will provide important additional protection for developing severe disease, although is less easily tested.”

As for the best vaccination strategies, Dr. Hill said “patients should get vaccinated as soon as they are eligible, according to standard guidelines. If patients have not yet started therapy, they should get their indicated vaccines before starting treatment whenever possible.”

The German study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Bavarian State Ministry of Science and Art. Dr. Wendtner disclosed consultant fees from AstraZeneca and BioNTech, and another author disclosed consultant fees from AstraZeneca. The other authors reported no disclosures. Dr. Hill disclosed consultant fees from Moderna, Pfizer, and Gilead.

While it’s well known that COVID-19 vaccines are less effective in patients with chronic lymphocytic leukemia (CLL) who take immunity-lowering drugs, a new study offers fresh insight into what’s happening inside the body. In these patients, the vaccines often don’t boost B cells, which produce antibodies, but they do strengthen T cells, potentially providing crucial protection against severe illness and death.

These findings don’t reveal whether the T-cell boost actually provides extra protection against COVID-19. Still, the study suggests that patients with CLL should be vaccinated no matter which medications they’re taking, coauthor and hematologist/oncologist Clemens-Martin Wendtner, MD, of the Munich (Germany) Clinic, said in an interview.

“Do not defer or pause treatment,” said Dr. Wendtner, whose study was published in Blood Advances.

Patients with CLL appear to have among the weakest responses to the COVID-19 vaccine among people with various types of blood cancer. A meta-analysis published in 2022 found that seropositivity rates following vaccination were just 51% in patients with CLL, compared with 80%-90% in those with acute leukemia and 76%-80% of those with myeloma.

“Usually, the response rate to vaccination among the nonimmunocompromised would be 95%,” Dr. Wendtner said.

Research has also suggested that patients treated with B-cell pathway inhibitors and anti-CD20 antibodies are especially likely to have poorer responses to COVID-19 vaccines, no surprise considering that their job is to dampen the immune system. But there’s an unanswered question, according to Dr. Wendtner: Does “just measuring B-cell response tell us everything about the immune response?”

The new prospective, single-institution study aims to answer that question in patients who each received two types of vaccines. Researchers compared peripheral blood mononuclear cell transcriptional response with antibody and T-cell response rates in 15 patients with CLL/small lymphocytic lymphoma following vaccination with both the Pfizer-BioNTech and AstraZeneca vaccines.

The average antibody response was limited. “Overall, 7/15 of patients failed to mount a humoral response even after three-dose vaccination,” the researchers reported. All of the patients were “heavily pretreated” with CLL medications such as venetoclax, an anti-CD20 monoclonal antibody.

By contrast, the T-cell response was much stronger: 80% of patients (12/15) had a robust response, a number that grew to 90% (14/15) after a booster. This response is “almost ideal” considering that the response in a nonimmunocompromised person would be about 99%, Dr. Wendtner said.

The study also revealed that vaccine responses were weaker in patients who took a combination of a Bruton tyrosine kinase inhibitor and venetoclax within a year.

Four patients developed COVID-19 infections with the Omicron variant about 6 months after vaccination. All had mild symptoms. A lone patient had a history of COVID-19 infection prior to vaccination.

The researchers noted that the study had several limitations, including its small size, its reliance on a single institution, and the differences in treatments and vaccination protocols among the patient population.

Broadly speaking, the study showed that “a vaccine is not in vain” in patients with CLL, “although the doctor might not detect an antibody response,” Dr. Wendtner said. He added that mixing vaccine types should provide more protection. Start with a viral vector vaccine followed by an mRNA vaccine or vice versa, he suggested.

In an interview, infectious disease physician Joshua A. Hill, MD, from Fred Hutchinson Cancer Center, Seattle, who wasn’t involved with the study, said it makes “important and interesting observations to reinforce other studies with similar findings.”

Specifically, Dr. Hill said, “despite the absence of a robust antibody response some of these patients who are on active treatment, patients can still generate robust cellular immune responses in the form of T-cell immunity. Our understanding is that having T cell immunity will provide important additional protection for developing severe disease, although is less easily tested.”

As for the best vaccination strategies, Dr. Hill said “patients should get vaccinated as soon as they are eligible, according to standard guidelines. If patients have not yet started therapy, they should get their indicated vaccines before starting treatment whenever possible.”

The German study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Bavarian State Ministry of Science and Art. Dr. Wendtner disclosed consultant fees from AstraZeneca and BioNTech, and another author disclosed consultant fees from AstraZeneca. The other authors reported no disclosures. Dr. Hill disclosed consultant fees from Moderna, Pfizer, and Gilead.

While it’s well known that COVID-19 vaccines are less effective in patients with chronic lymphocytic leukemia (CLL) who take immunity-lowering drugs, a new study offers fresh insight into what’s happening inside the body. In these patients, the vaccines often don’t boost B cells, which produce antibodies, but they do strengthen T cells, potentially providing crucial protection against severe illness and death.

These findings don’t reveal whether the T-cell boost actually provides extra protection against COVID-19. Still, the study suggests that patients with CLL should be vaccinated no matter which medications they’re taking, coauthor and hematologist/oncologist Clemens-Martin Wendtner, MD, of the Munich (Germany) Clinic, said in an interview.

“Do not defer or pause treatment,” said Dr. Wendtner, whose study was published in Blood Advances.

Patients with CLL appear to have among the weakest responses to the COVID-19 vaccine among people with various types of blood cancer. A meta-analysis published in 2022 found that seropositivity rates following vaccination were just 51% in patients with CLL, compared with 80%-90% in those with acute leukemia and 76%-80% of those with myeloma.

“Usually, the response rate to vaccination among the nonimmunocompromised would be 95%,” Dr. Wendtner said.

Research has also suggested that patients treated with B-cell pathway inhibitors and anti-CD20 antibodies are especially likely to have poorer responses to COVID-19 vaccines, no surprise considering that their job is to dampen the immune system. But there’s an unanswered question, according to Dr. Wendtner: Does “just measuring B-cell response tell us everything about the immune response?”

The new prospective, single-institution study aims to answer that question in patients who each received two types of vaccines. Researchers compared peripheral blood mononuclear cell transcriptional response with antibody and T-cell response rates in 15 patients with CLL/small lymphocytic lymphoma following vaccination with both the Pfizer-BioNTech and AstraZeneca vaccines.

The average antibody response was limited. “Overall, 7/15 of patients failed to mount a humoral response even after three-dose vaccination,” the researchers reported. All of the patients were “heavily pretreated” with CLL medications such as venetoclax, an anti-CD20 monoclonal antibody.

By contrast, the T-cell response was much stronger: 80% of patients (12/15) had a robust response, a number that grew to 90% (14/15) after a booster. This response is “almost ideal” considering that the response in a nonimmunocompromised person would be about 99%, Dr. Wendtner said.

The study also revealed that vaccine responses were weaker in patients who took a combination of a Bruton tyrosine kinase inhibitor and venetoclax within a year.

Four patients developed COVID-19 infections with the Omicron variant about 6 months after vaccination. All had mild symptoms. A lone patient had a history of COVID-19 infection prior to vaccination.

The researchers noted that the study had several limitations, including its small size, its reliance on a single institution, and the differences in treatments and vaccination protocols among the patient population.

Broadly speaking, the study showed that “a vaccine is not in vain” in patients with CLL, “although the doctor might not detect an antibody response,” Dr. Wendtner said. He added that mixing vaccine types should provide more protection. Start with a viral vector vaccine followed by an mRNA vaccine or vice versa, he suggested.

In an interview, infectious disease physician Joshua A. Hill, MD, from Fred Hutchinson Cancer Center, Seattle, who wasn’t involved with the study, said it makes “important and interesting observations to reinforce other studies with similar findings.”

Specifically, Dr. Hill said, “despite the absence of a robust antibody response some of these patients who are on active treatment, patients can still generate robust cellular immune responses in the form of T-cell immunity. Our understanding is that having T cell immunity will provide important additional protection for developing severe disease, although is less easily tested.”

As for the best vaccination strategies, Dr. Hill said “patients should get vaccinated as soon as they are eligible, according to standard guidelines. If patients have not yet started therapy, they should get their indicated vaccines before starting treatment whenever possible.”

The German study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Bavarian State Ministry of Science and Art. Dr. Wendtner disclosed consultant fees from AstraZeneca and BioNTech, and another author disclosed consultant fees from AstraZeneca. The other authors reported no disclosures. Dr. Hill disclosed consultant fees from Moderna, Pfizer, and Gilead.

Opioids are widely regarded as a linchpin in the treatment of moderate to severe cancer-related pain and end-of-life symptoms; however, there are persistent racial and ethnic inequities in opioid access among older cancer patients, with Black patients being disproportionately affected, a new study suggests.

Black patients were more likely to undergo urine drug screening (UDS) despite being less likely to receive any opioids for pain management and receiving lower daily doses of opioids in comparison with White patients, the study found.

The inequities were particularly stark for Black men. “We found that Black men were far less likely to be prescribed reasonable doses than White men were,” said the study’s senior author, Alexi Wright, MD, MPH, a gynecologic oncologist and a researcher in the division of population sciences at Dana-Farber Cancer Institute, Boston. “And Black men were less likely to receive long-acting opioids, which are essential for many patients dying of cancer. Our findings are startling because everyone should agree that cancer patients should have equal access to pain relief at the end of life.”

The study was published on in the Journal of Clinical Oncology.

The researchers gathered data on 318,549 Medicare beneficiaries older than 65 years with poor-prognosis cancers who died between 2007 and 2019. During this time frame, for all groups, access to opioids declined and urine drug testing expanded, owing to the overall opioid epidemic in the United States. Overall, the proportion of patients near end of life (EOL) who received any opioid or long-acting opioids decreased from 42.2% to 32.7% and from 17.9% to 9.4%, respectively.

The investigators used National Drug Codes to identify all Medicare Part D claims for outpatient opioid prescriptions, excluding addiction treatments, cough suppressants, and parenteral opioids. They focused on prescriptions that were filled at least 30 days before death or hospice enrollment.

Among the study participants, the majority (85.5%) of patients were White, 29,555 patients (9.3%) were Black, and 16,636 patients (5.2%) were Hispanic.

Black and Hispanic patients were statistically less likely than White patients to receive opioid prescriptions near EOL (Black, –4.3 percentage points; Hispanic, –3.6 percentage points). They were also less likely to receive long-acting opioid prescriptions (Black, –3.1 percentage points; Hispanic, –2.2 percentage points).

“It’s not just that patients of color are less likely to get opioids, but when they do get them, they get lower doses, and they also are less likely to get long-acting opioids, which a lot of people view as sort of more potential for addiction, which isn’t necessarily true but kind of viewed with heightened concern or suspicion,” the study’s lead author, Andrea Enzinger, MD, a gastrointestinal oncologist and a researcher in Dana-Farber’s division of population sciences, said in an interview.

Dr. Enzinger added that she believes systemic racism and preconceived biases toward minorities and drug addiction may be contributing to these trends.

When Black patients did receive at least one opioid prescription, they received daily doses that were 10.5 morphine milligram equivalents (MMEs) lower than doses given to White patients. Compared with the total opioid dose filled per White decedent near EOL, the total dose filled per Black decedent was 210 MMEs lower.

“We all need to be worried about the potential for misuse or addiction, but this is the one setting that is very low on my priority list when somebody is dying. I mean, we’re looking at the last month of life, so nobody has the potential to become addicted,” Dr. Enzinger commented.

The team also evaluated rates or urine drug screening (UDS), but as these rates were relatively low, they expanded the time frame to 180 days before death or hospice. They found that disparities in UDS disproportionately affected Black men.

From 2007 to 2019, the proportion of patients who underwent UDS increased from 0.6% to 6.7% in the 180 days before death or hospice; however, Black decedents were tested more often than White or Hispanic decedents.

Black decedents were 0.5 percentage points more likely than White decedents to undergo UDS near EOL.

“The disparities in urine drug screening are modest but important, because they hint at underlying systematic racism in recommending patients for screening,” Dr. Wright said. “Screening needs to either be applied uniformly or not at all for patients in this situation.”

The researchers acknowledged that their findings likely do not represent the full spectrum of prescribing disparities and believe that the work should be expanded among younger populations. Nevertheless, the investigators believe the work highlights the persistent racial and ethnic disparities in opioid access.

The study was supported by a grant from the Agency for Healthcare Research and Policy.

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

Opioids are widely regarded as a linchpin in the treatment of moderate to severe cancer-related pain and end-of-life symptoms; however, there are persistent racial and ethnic inequities in opioid access among older cancer patients, with Black patients being disproportionately affected, a new study suggests.

Black patients were more likely to undergo urine drug screening (UDS) despite being less likely to receive any opioids for pain management and receiving lower daily doses of opioids in comparison with White patients, the study found.

The inequities were particularly stark for Black men. “We found that Black men were far less likely to be prescribed reasonable doses than White men were,” said the study’s senior author, Alexi Wright, MD, MPH, a gynecologic oncologist and a researcher in the division of population sciences at Dana-Farber Cancer Institute, Boston. “And Black men were less likely to receive long-acting opioids, which are essential for many patients dying of cancer. Our findings are startling because everyone should agree that cancer patients should have equal access to pain relief at the end of life.”

The study was published on in the Journal of Clinical Oncology.

The researchers gathered data on 318,549 Medicare beneficiaries older than 65 years with poor-prognosis cancers who died between 2007 and 2019. During this time frame, for all groups, access to opioids declined and urine drug testing expanded, owing to the overall opioid epidemic in the United States. Overall, the proportion of patients near end of life (EOL) who received any opioid or long-acting opioids decreased from 42.2% to 32.7% and from 17.9% to 9.4%, respectively.

The investigators used National Drug Codes to identify all Medicare Part D claims for outpatient opioid prescriptions, excluding addiction treatments, cough suppressants, and parenteral opioids. They focused on prescriptions that were filled at least 30 days before death or hospice enrollment.

Among the study participants, the majority (85.5%) of patients were White, 29,555 patients (9.3%) were Black, and 16,636 patients (5.2%) were Hispanic.

Black and Hispanic patients were statistically less likely than White patients to receive opioid prescriptions near EOL (Black, –4.3 percentage points; Hispanic, –3.6 percentage points). They were also less likely to receive long-acting opioid prescriptions (Black, –3.1 percentage points; Hispanic, –2.2 percentage points).

“It’s not just that patients of color are less likely to get opioids, but when they do get them, they get lower doses, and they also are less likely to get long-acting opioids, which a lot of people view as sort of more potential for addiction, which isn’t necessarily true but kind of viewed with heightened concern or suspicion,” the study’s lead author, Andrea Enzinger, MD, a gastrointestinal oncologist and a researcher in Dana-Farber’s division of population sciences, said in an interview.

Dr. Enzinger added that she believes systemic racism and preconceived biases toward minorities and drug addiction may be contributing to these trends.

When Black patients did receive at least one opioid prescription, they received daily doses that were 10.5 morphine milligram equivalents (MMEs) lower than doses given to White patients. Compared with the total opioid dose filled per White decedent near EOL, the total dose filled per Black decedent was 210 MMEs lower.

“We all need to be worried about the potential for misuse or addiction, but this is the one setting that is very low on my priority list when somebody is dying. I mean, we’re looking at the last month of life, so nobody has the potential to become addicted,” Dr. Enzinger commented.

The team also evaluated rates or urine drug screening (UDS), but as these rates were relatively low, they expanded the time frame to 180 days before death or hospice. They found that disparities in UDS disproportionately affected Black men.

From 2007 to 2019, the proportion of patients who underwent UDS increased from 0.6% to 6.7% in the 180 days before death or hospice; however, Black decedents were tested more often than White or Hispanic decedents.

Black decedents were 0.5 percentage points more likely than White decedents to undergo UDS near EOL.

“The disparities in urine drug screening are modest but important, because they hint at underlying systematic racism in recommending patients for screening,” Dr. Wright said. “Screening needs to either be applied uniformly or not at all for patients in this situation.”

The researchers acknowledged that their findings likely do not represent the full spectrum of prescribing disparities and believe that the work should be expanded among younger populations. Nevertheless, the investigators believe the work highlights the persistent racial and ethnic disparities in opioid access.

The study was supported by a grant from the Agency for Healthcare Research and Policy.

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

Opioids are widely regarded as a linchpin in the treatment of moderate to severe cancer-related pain and end-of-life symptoms; however, there are persistent racial and ethnic inequities in opioid access among older cancer patients, with Black patients being disproportionately affected, a new study suggests.

Black patients were more likely to undergo urine drug screening (UDS) despite being less likely to receive any opioids for pain management and receiving lower daily doses of opioids in comparison with White patients, the study found.

The inequities were particularly stark for Black men. “We found that Black men were far less likely to be prescribed reasonable doses than White men were,” said the study’s senior author, Alexi Wright, MD, MPH, a gynecologic oncologist and a researcher in the division of population sciences at Dana-Farber Cancer Institute, Boston. “And Black men were less likely to receive long-acting opioids, which are essential for many patients dying of cancer. Our findings are startling because everyone should agree that cancer patients should have equal access to pain relief at the end of life.”

The study was published on in the Journal of Clinical Oncology.

The researchers gathered data on 318,549 Medicare beneficiaries older than 65 years with poor-prognosis cancers who died between 2007 and 2019. During this time frame, for all groups, access to opioids declined and urine drug testing expanded, owing to the overall opioid epidemic in the United States. Overall, the proportion of patients near end of life (EOL) who received any opioid or long-acting opioids decreased from 42.2% to 32.7% and from 17.9% to 9.4%, respectively.

The investigators used National Drug Codes to identify all Medicare Part D claims for outpatient opioid prescriptions, excluding addiction treatments, cough suppressants, and parenteral opioids. They focused on prescriptions that were filled at least 30 days before death or hospice enrollment.

Among the study participants, the majority (85.5%) of patients were White, 29,555 patients (9.3%) were Black, and 16,636 patients (5.2%) were Hispanic.

Black and Hispanic patients were statistically less likely than White patients to receive opioid prescriptions near EOL (Black, –4.3 percentage points; Hispanic, –3.6 percentage points). They were also less likely to receive long-acting opioid prescriptions (Black, –3.1 percentage points; Hispanic, –2.2 percentage points).

“It’s not just that patients of color are less likely to get opioids, but when they do get them, they get lower doses, and they also are less likely to get long-acting opioids, which a lot of people view as sort of more potential for addiction, which isn’t necessarily true but kind of viewed with heightened concern or suspicion,” the study’s lead author, Andrea Enzinger, MD, a gastrointestinal oncologist and a researcher in Dana-Farber’s division of population sciences, said in an interview.

Dr. Enzinger added that she believes systemic racism and preconceived biases toward minorities and drug addiction may be contributing to these trends.

When Black patients did receive at least one opioid prescription, they received daily doses that were 10.5 morphine milligram equivalents (MMEs) lower than doses given to White patients. Compared with the total opioid dose filled per White decedent near EOL, the total dose filled per Black decedent was 210 MMEs lower.

“We all need to be worried about the potential for misuse or addiction, but this is the one setting that is very low on my priority list when somebody is dying. I mean, we’re looking at the last month of life, so nobody has the potential to become addicted,” Dr. Enzinger commented.

The team also evaluated rates or urine drug screening (UDS), but as these rates were relatively low, they expanded the time frame to 180 days before death or hospice. They found that disparities in UDS disproportionately affected Black men.

From 2007 to 2019, the proportion of patients who underwent UDS increased from 0.6% to 6.7% in the 180 days before death or hospice; however, Black decedents were tested more often than White or Hispanic decedents.

Black decedents were 0.5 percentage points more likely than White decedents to undergo UDS near EOL.

“The disparities in urine drug screening are modest but important, because they hint at underlying systematic racism in recommending patients for screening,” Dr. Wright said. “Screening needs to either be applied uniformly or not at all for patients in this situation.”

The researchers acknowledged that their findings likely do not represent the full spectrum of prescribing disparities and believe that the work should be expanded among younger populations. Nevertheless, the investigators believe the work highlights the persistent racial and ethnic disparities in opioid access.

The study was supported by a grant from the Agency for Healthcare Research and Policy.

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

Young adults who survive cancer are more likely than cancer-free siblings to be lonely and to develop emotional distress, risky behaviors, and new chronic conditions as a result, findings from a large retrospective study suggest.

Young cancer survivors were more than twice as likely to report loneliness at study baseline and follow-up. Loneliness at these times was associated with an almost 10-fold increased risk for anxiety and a nearly 18-fold increased risk for depression.

“We observed an elevated prevalence of loneliness in survivors, compared to sibling controls, and found that loneliness was associated with emotional, behavioral, and physical health morbidities,” lead study author Chiara Papini, PhD, of St. Jude Children’s Research Hospital, Memphis, and her colleagues write. “Our results highlight the importance of identifying and screening young adult survivors of childhood cancer for loneliness and the need for targeted interventions to reduce loneliness.”

The article was published online in the journal Cancer.

Most young cancer survivors in the United States reach adulthood and need to play catch-up: make up for missed school and work, become reacquainted with old friends, and develop new friendships, social networks, and intimate relationships. Meeting these needs may be hindered by adverse physical and psychosocial problems that linger or develop after treatment, which may leave cancer survivors feeling isolated.

“Young adult survivors of childhood cancer are navigating a developmental period marked by increased social expectations, during which loneliness may have significant impact on physical and mental health,” Dr. Papini and colleagues say.

To better understand the risks for loneliness among young cancer survivors, Dr. Papini and her colleagues analyzed data from the retrospective Childhood Cancer Survivor Study, which followed young survivors who had been diagnosed with a range of cancers before age 21 years. Study participants had been treated at one of 31 study sites in North America and had survived 5 years or longer after diagnosis.

The 9,664 survivors and 2,221 randomly sampled siblings ranged in age from 19 to 39 years at the time they completed a survey that assessed emotional distress at baseline and at follow‐up a median of 6.6 years. At baseline, the median age of the survivors was 27 years, and a median of 17.5 years had passed from the time of their diagnosis.

The most common diagnoses were leukemia (35%), Hodgkin lymphoma (15%), central nervous system (CNS) tumors (14%), and bone tumors (10%). More than half (56%) had received radiation therapy.

Using multivariable models, the researchers found that survivors were more likely than siblings to report moderate to extreme loneliness at either baseline or follow‐up (prevalence ratio, 1.04) and were more than two times more likely to report loneliness at both baseline and follow‐up (PR, 2.21).

Loneliness at baseline and follow‐up was associated with a much greater risk for anxiety (relative risk, 9.75) and depression (RR, 17.86). Loneliness at follow‐up was linked with increased risks for suicidal ideation (RR, 1.52), heavy or risky alcohol consumption (RR, 1.27), and any grade 2-4 new‐onset chronic health condition (RR, 1.29), especially those that were neurologic (RR, 4.37).

Survivors of CNS tumors (odds ratio, 2.59) and leukemia (OR, 2.52) were most likely to report loneliness at both baseline and follow‐up, though survivors of four other cancer types also faced an elevated risk for loneliness: neuroblastoma (OR, 2.32), bone tumor (OR, 2.12), soft tissue sarcoma (OR, 1.78), and Hodgkin lymphoma (OR, 1.69).

Treatment type appeared to matter as well. Survivors who underwent amputation (OR, 1.82) or were treated with cranial radiation greater than or equal to 20 Gy (OR, 1.56) or corticosteroids (OR, 1.31) were more likely to report loneliness at baseline and follow‐up, compared with those who reported no loneliness at both time points.

The authors acknowledge limitations to the study, including the fact that roughly 90% of survivors and siblings were White, which limits the applicability of their results to diverse groups. In addition, the responses were self-reported without external validation.

Overall, though, the findings provide a framework for clinicians to understand and identify loneliness among young cancer survivors and help them cope with their emotions.

“The Childhood Cancer Survivor Study provides the largest and the most comprehensive dataset on childhood cancer survivors and healthy-sibling comparisons, giving us powerful data on survivorship, late effects, and psychosocial and health outcomes,” Rachel M. Moore, PhD, child psychologist at Children’s Mercy Kansas City, Mo., said in an interview.

Asking a simple question – “Are you feeling lonely?” – can identify at-risk survivors and enable health care teams to provide timely interventions that address young patients’ physical and psychological needs, said Dr. Moore, who was not involved in the study.

Dr. Moore noted that within her clinical practice, “adolescent and young adult survivors frequently discuss loneliness in their daily lives. They feel different from their peers and misunderstood. Having a conversation early in survivorship care about the experience of loneliness as a product of cancer treatment can open the door to regular screening and destigmatizing mental health services.”

Supporting young people throughout their survivorship journey is important, said Rusha Bhandari, MD, medical director of the Childhood, Adolescent, and Young Adult Cancer Survivorship Program at City of Hope, Duarte, Calif. This study can help ensure that clinicians “provide comprehensive care, including psychosocial screening and support, to meet the unique needs of our young adult survivors,” said Dr. Bhandari, who also was not involved in the research.

The National Cancer Institute and the American Lebanese Syrian Associated Charities supported the study. One co-author reported receiving corporate consulting fees. Dr. Papini, the remaining co-authors, Dr. Moore, and Dr. Bhandari report no relevant financial involvements.

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

Young adults who survive cancer are more likely than cancer-free siblings to be lonely and to develop emotional distress, risky behaviors, and new chronic conditions as a result, findings from a large retrospective study suggest.

Young cancer survivors were more than twice as likely to report loneliness at study baseline and follow-up. Loneliness at these times was associated with an almost 10-fold increased risk for anxiety and a nearly 18-fold increased risk for depression.

“We observed an elevated prevalence of loneliness in survivors, compared to sibling controls, and found that loneliness was associated with emotional, behavioral, and physical health morbidities,” lead study author Chiara Papini, PhD, of St. Jude Children’s Research Hospital, Memphis, and her colleagues write. “Our results highlight the importance of identifying and screening young adult survivors of childhood cancer for loneliness and the need for targeted interventions to reduce loneliness.”

The article was published online in the journal Cancer.

Most young cancer survivors in the United States reach adulthood and need to play catch-up: make up for missed school and work, become reacquainted with old friends, and develop new friendships, social networks, and intimate relationships. Meeting these needs may be hindered by adverse physical and psychosocial problems that linger or develop after treatment, which may leave cancer survivors feeling isolated.

“Young adult survivors of childhood cancer are navigating a developmental period marked by increased social expectations, during which loneliness may have significant impact on physical and mental health,” Dr. Papini and colleagues say.

To better understand the risks for loneliness among young cancer survivors, Dr. Papini and her colleagues analyzed data from the retrospective Childhood Cancer Survivor Study, which followed young survivors who had been diagnosed with a range of cancers before age 21 years. Study participants had been treated at one of 31 study sites in North America and had survived 5 years or longer after diagnosis.

The 9,664 survivors and 2,221 randomly sampled siblings ranged in age from 19 to 39 years at the time they completed a survey that assessed emotional distress at baseline and at follow‐up a median of 6.6 years. At baseline, the median age of the survivors was 27 years, and a median of 17.5 years had passed from the time of their diagnosis.

The most common diagnoses were leukemia (35%), Hodgkin lymphoma (15%), central nervous system (CNS) tumors (14%), and bone tumors (10%). More than half (56%) had received radiation therapy.

Using multivariable models, the researchers found that survivors were more likely than siblings to report moderate to extreme loneliness at either baseline or follow‐up (prevalence ratio, 1.04) and were more than two times more likely to report loneliness at both baseline and follow‐up (PR, 2.21).

Loneliness at baseline and follow‐up was associated with a much greater risk for anxiety (relative risk, 9.75) and depression (RR, 17.86). Loneliness at follow‐up was linked with increased risks for suicidal ideation (RR, 1.52), heavy or risky alcohol consumption (RR, 1.27), and any grade 2-4 new‐onset chronic health condition (RR, 1.29), especially those that were neurologic (RR, 4.37).

Survivors of CNS tumors (odds ratio, 2.59) and leukemia (OR, 2.52) were most likely to report loneliness at both baseline and follow‐up, though survivors of four other cancer types also faced an elevated risk for loneliness: neuroblastoma (OR, 2.32), bone tumor (OR, 2.12), soft tissue sarcoma (OR, 1.78), and Hodgkin lymphoma (OR, 1.69).

Treatment type appeared to matter as well. Survivors who underwent amputation (OR, 1.82) or were treated with cranial radiation greater than or equal to 20 Gy (OR, 1.56) or corticosteroids (OR, 1.31) were more likely to report loneliness at baseline and follow‐up, compared with those who reported no loneliness at both time points.

The authors acknowledge limitations to the study, including the fact that roughly 90% of survivors and siblings were White, which limits the applicability of their results to diverse groups. In addition, the responses were self-reported without external validation.

Overall, though, the findings provide a framework for clinicians to understand and identify loneliness among young cancer survivors and help them cope with their emotions.

“The Childhood Cancer Survivor Study provides the largest and the most comprehensive dataset on childhood cancer survivors and healthy-sibling comparisons, giving us powerful data on survivorship, late effects, and psychosocial and health outcomes,” Rachel M. Moore, PhD, child psychologist at Children’s Mercy Kansas City, Mo., said in an interview.

Asking a simple question – “Are you feeling lonely?” – can identify at-risk survivors and enable health care teams to provide timely interventions that address young patients’ physical and psychological needs, said Dr. Moore, who was not involved in the study.

Dr. Moore noted that within her clinical practice, “adolescent and young adult survivors frequently discuss loneliness in their daily lives. They feel different from their peers and misunderstood. Having a conversation early in survivorship care about the experience of loneliness as a product of cancer treatment can open the door to regular screening and destigmatizing mental health services.”

Supporting young people throughout their survivorship journey is important, said Rusha Bhandari, MD, medical director of the Childhood, Adolescent, and Young Adult Cancer Survivorship Program at City of Hope, Duarte, Calif. This study can help ensure that clinicians “provide comprehensive care, including psychosocial screening and support, to meet the unique needs of our young adult survivors,” said Dr. Bhandari, who also was not involved in the research.

The National Cancer Institute and the American Lebanese Syrian Associated Charities supported the study. One co-author reported receiving corporate consulting fees. Dr. Papini, the remaining co-authors, Dr. Moore, and Dr. Bhandari report no relevant financial involvements.

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

Young adults who survive cancer are more likely than cancer-free siblings to be lonely and to develop emotional distress, risky behaviors, and new chronic conditions as a result, findings from a large retrospective study suggest.

Young cancer survivors were more than twice as likely to report loneliness at study baseline and follow-up. Loneliness at these times was associated with an almost 10-fold increased risk for anxiety and a nearly 18-fold increased risk for depression.

“We observed an elevated prevalence of loneliness in survivors, compared to sibling controls, and found that loneliness was associated with emotional, behavioral, and physical health morbidities,” lead study author Chiara Papini, PhD, of St. Jude Children’s Research Hospital, Memphis, and her colleagues write. “Our results highlight the importance of identifying and screening young adult survivors of childhood cancer for loneliness and the need for targeted interventions to reduce loneliness.”

The article was published online in the journal Cancer.

Most young cancer survivors in the United States reach adulthood and need to play catch-up: make up for missed school and work, become reacquainted with old friends, and develop new friendships, social networks, and intimate relationships. Meeting these needs may be hindered by adverse physical and psychosocial problems that linger or develop after treatment, which may leave cancer survivors feeling isolated.

“Young adult survivors of childhood cancer are navigating a developmental period marked by increased social expectations, during which loneliness may have significant impact on physical and mental health,” Dr. Papini and colleagues say.

To better understand the risks for loneliness among young cancer survivors, Dr. Papini and her colleagues analyzed data from the retrospective Childhood Cancer Survivor Study, which followed young survivors who had been diagnosed with a range of cancers before age 21 years. Study participants had been treated at one of 31 study sites in North America and had survived 5 years or longer after diagnosis.

The 9,664 survivors and 2,221 randomly sampled siblings ranged in age from 19 to 39 years at the time they completed a survey that assessed emotional distress at baseline and at follow‐up a median of 6.6 years. At baseline, the median age of the survivors was 27 years, and a median of 17.5 years had passed from the time of their diagnosis.

The most common diagnoses were leukemia (35%), Hodgkin lymphoma (15%), central nervous system (CNS) tumors (14%), and bone tumors (10%). More than half (56%) had received radiation therapy.

Using multivariable models, the researchers found that survivors were more likely than siblings to report moderate to extreme loneliness at either baseline or follow‐up (prevalence ratio, 1.04) and were more than two times more likely to report loneliness at both baseline and follow‐up (PR, 2.21).

Loneliness at baseline and follow‐up was associated with a much greater risk for anxiety (relative risk, 9.75) and depression (RR, 17.86). Loneliness at follow‐up was linked with increased risks for suicidal ideation (RR, 1.52), heavy or risky alcohol consumption (RR, 1.27), and any grade 2-4 new‐onset chronic health condition (RR, 1.29), especially those that were neurologic (RR, 4.37).

Survivors of CNS tumors (odds ratio, 2.59) and leukemia (OR, 2.52) were most likely to report loneliness at both baseline and follow‐up, though survivors of four other cancer types also faced an elevated risk for loneliness: neuroblastoma (OR, 2.32), bone tumor (OR, 2.12), soft tissue sarcoma (OR, 1.78), and Hodgkin lymphoma (OR, 1.69).

Treatment type appeared to matter as well. Survivors who underwent amputation (OR, 1.82) or were treated with cranial radiation greater than or equal to 20 Gy (OR, 1.56) or corticosteroids (OR, 1.31) were more likely to report loneliness at baseline and follow‐up, compared with those who reported no loneliness at both time points.

The authors acknowledge limitations to the study, including the fact that roughly 90% of survivors and siblings were White, which limits the applicability of their results to diverse groups. In addition, the responses were self-reported without external validation.

Overall, though, the findings provide a framework for clinicians to understand and identify loneliness among young cancer survivors and help them cope with their emotions.

“The Childhood Cancer Survivor Study provides the largest and the most comprehensive dataset on childhood cancer survivors and healthy-sibling comparisons, giving us powerful data on survivorship, late effects, and psychosocial and health outcomes,” Rachel M. Moore, PhD, child psychologist at Children’s Mercy Kansas City, Mo., said in an interview.

Asking a simple question – “Are you feeling lonely?” – can identify at-risk survivors and enable health care teams to provide timely interventions that address young patients’ physical and psychological needs, said Dr. Moore, who was not involved in the study.

Dr. Moore noted that within her clinical practice, “adolescent and young adult survivors frequently discuss loneliness in their daily lives. They feel different from their peers and misunderstood. Having a conversation early in survivorship care about the experience of loneliness as a product of cancer treatment can open the door to regular screening and destigmatizing mental health services.”

Supporting young people throughout their survivorship journey is important, said Rusha Bhandari, MD, medical director of the Childhood, Adolescent, and Young Adult Cancer Survivorship Program at City of Hope, Duarte, Calif. This study can help ensure that clinicians “provide comprehensive care, including psychosocial screening and support, to meet the unique needs of our young adult survivors,” said Dr. Bhandari, who also was not involved in the research.

The National Cancer Institute and the American Lebanese Syrian Associated Charities supported the study. One co-author reported receiving corporate consulting fees. Dr. Papini, the remaining co-authors, Dr. Moore, and Dr. Bhandari report no relevant financial involvements.

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

Female physicians often spend their child-bearing years in medical training and developing their careers, and this can create problems.  

In a survey of just over 1,000 female oncologists, 95% said their career plans were at least somewhat associated with the timing of when to start a family.

The most striking finding was that one third of respondents had miscarried and another one third reported difficulty with infertility that required fertility counseling and/or treatment.

One third reported experiencing discrimination during pregnancy, and another third said they experienced discrimination for taking maternity leave, and having more than one child increased the likelihood of this.

The most common negative factor associated with family planning was long work hours and heavy workload (66.6%),

These findings suggest there are systemic changes needed not only in the healthcare setting but in society as a whole around women in the workplace and their choices of childbearing, say the authors.

The study was published online in JAMA Network Open and led by Anna Lee MD, MPH, from the department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston. 

In an invited commentary, Mona Saleh, MD, and Stephanie Blank, MD, from the department of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai in New York, suggest that cultural changes are needed that go beyond women in medicine.

“These cultural values are so deeply pervasive (one could also say invasive) that they affect even these most educated and wealthy professional women, such as those who participated in this survey,” the editorialists write.

“[The researchers] advocate for early education on assisted reproductive technology (ART) risks, benefits, and success rates, but this is not getting at the underlying issue: Pregnancy discrimination and unfair distribution of childbearing responsibilities are a reflection of a larger problematic culture rather than an issue specific to women in medicine,” they add.
 

Survey details

The survey comprised a novel 39-item questionnaire distributed to 1,004 U.S. female oncologists from May 7 to June 30, 2020, via email and social media channels.

Most respondents (84.4%) were married, and 71% were currently working full-time.

About one-third (35%) worked in radiation oncology, another third (34.3%) in medical oncology, 18.4% in surgical oncology, and 9.1% in pediatric oncology.

A total of 768 respondents (76.5%) had children, and of these, 415 (41.3%) first gave birth during postgraduate training and 275 (27.4%) gave birth in years 1-5 as an attending physician.

Of all respondents who had been pregnant, approximately two-thirds (65.7%) had some type of pregnancy complication. About one-third of respondents (31.7%) reported having experienced a miscarriage after a confirmed pregnancy; of those, 61.6% reported one miscarriage, while the remainder had two or more miscarriages (38.4%).

Approximately one-third (31.4%) of respondents reported difficulty with infertility that required fertility counseling and/or treatment.

The questionnaire also asked about assisted reproductive technology, and 164 participants (16.3%) reported the use of fertility medications, and 53 (5.3%) reported cryopreservation of eggs. Nearly 13% reported the use of intrauterine insemination and 13.2% reported the use of in vivo fertilization. Among those who experienced fertility concerns, 36.6% (232 of 634) reported facing financial burdens because of fertility or pregnancy that was in some way associated with their career choice.

When asked on the survey if fertility preservation should be discussed with women during medical school and/or residency, 65.7% of respondents stated that it should.

However, the editorialists suggest that “encouraging formal and directed education regarding the infertility risks specifically toward female physicians (which Lee et al. recommend) could be perceived as a blanket recommendation that it is best for women in medicine to delay childbearing and pursue ART.”

“Medical schools and residency and fellowship training programs should instead focus their energy on creating a framework and culture that normalizes conception during these points in training while also subsidizing and supporting trainees and physicians who prefer to use ART and delay fertility until after training,” they suggest.

The editorialists also emphasized that women may choose to become pregnant at any point during the years that it takes to go from being a medical student to resident/fellow to attending physician, and they should be supported by their workplace on their decisions.

The study was funded by grants from National Institutes of Health/National Cancer Institute Cancer Center.

Dr. Lee and coauthors reported no relevant financial relationships. Dr. Blank reported receiving grants from AstraZeneca, Aravive, Akesobio, GlaxoSmithKline, Merck, and Seattle Genetics outside the submitted work. Dr. Saleh reports no relevant financial relationships.

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

Female physicians often spend their child-bearing years in medical training and developing their careers, and this can create problems.  

In a survey of just over 1,000 female oncologists, 95% said their career plans were at least somewhat associated with the timing of when to start a family.

The most striking finding was that one third of respondents had miscarried and another one third reported difficulty with infertility that required fertility counseling and/or treatment.

One third reported experiencing discrimination during pregnancy, and another third said they experienced discrimination for taking maternity leave, and having more than one child increased the likelihood of this.

The most common negative factor associated with family planning was long work hours and heavy workload (66.6%),

These findings suggest there are systemic changes needed not only in the healthcare setting but in society as a whole around women in the workplace and their choices of childbearing, say the authors.

The study was published online in JAMA Network Open and led by Anna Lee MD, MPH, from the department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston. 

In an invited commentary, Mona Saleh, MD, and Stephanie Blank, MD, from the department of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai in New York, suggest that cultural changes are needed that go beyond women in medicine.

“These cultural values are so deeply pervasive (one could also say invasive) that they affect even these most educated and wealthy professional women, such as those who participated in this survey,” the editorialists write.

“[The researchers] advocate for early education on assisted reproductive technology (ART) risks, benefits, and success rates, but this is not getting at the underlying issue: Pregnancy discrimination and unfair distribution of childbearing responsibilities are a reflection of a larger problematic culture rather than an issue specific to women in medicine,” they add.
 

Survey details

The survey comprised a novel 39-item questionnaire distributed to 1,004 U.S. female oncologists from May 7 to June 30, 2020, via email and social media channels.

Most respondents (84.4%) were married, and 71% were currently working full-time.

About one-third (35%) worked in radiation oncology, another third (34.3%) in medical oncology, 18.4% in surgical oncology, and 9.1% in pediatric oncology.

A total of 768 respondents (76.5%) had children, and of these, 415 (41.3%) first gave birth during postgraduate training and 275 (27.4%) gave birth in years 1-5 as an attending physician.

Of all respondents who had been pregnant, approximately two-thirds (65.7%) had some type of pregnancy complication. About one-third of respondents (31.7%) reported having experienced a miscarriage after a confirmed pregnancy; of those, 61.6% reported one miscarriage, while the remainder had two or more miscarriages (38.4%).

Approximately one-third (31.4%) of respondents reported difficulty with infertility that required fertility counseling and/or treatment.

The questionnaire also asked about assisted reproductive technology, and 164 participants (16.3%) reported the use of fertility medications, and 53 (5.3%) reported cryopreservation of eggs. Nearly 13% reported the use of intrauterine insemination and 13.2% reported the use of in vivo fertilization. Among those who experienced fertility concerns, 36.6% (232 of 634) reported facing financial burdens because of fertility or pregnancy that was in some way associated with their career choice.

When asked on the survey if fertility preservation should be discussed with women during medical school and/or residency, 65.7% of respondents stated that it should.

However, the editorialists suggest that “encouraging formal and directed education regarding the infertility risks specifically toward female physicians (which Lee et al. recommend) could be perceived as a blanket recommendation that it is best for women in medicine to delay childbearing and pursue ART.”

“Medical schools and residency and fellowship training programs should instead focus their energy on creating a framework and culture that normalizes conception during these points in training while also subsidizing and supporting trainees and physicians who prefer to use ART and delay fertility until after training,” they suggest.

The editorialists also emphasized that women may choose to become pregnant at any point during the years that it takes to go from being a medical student to resident/fellow to attending physician, and they should be supported by their workplace on their decisions.

The study was funded by grants from National Institutes of Health/National Cancer Institute Cancer Center.

Dr. Lee and coauthors reported no relevant financial relationships. Dr. Blank reported receiving grants from AstraZeneca, Aravive, Akesobio, GlaxoSmithKline, Merck, and Seattle Genetics outside the submitted work. Dr. Saleh reports no relevant financial relationships.

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

Female physicians often spend their child-bearing years in medical training and developing their careers, and this can create problems.  

In a survey of just over 1,000 female oncologists, 95% said their career plans were at least somewhat associated with the timing of when to start a family.

The most striking finding was that one third of respondents had miscarried and another one third reported difficulty with infertility that required fertility counseling and/or treatment.

One third reported experiencing discrimination during pregnancy, and another third said they experienced discrimination for taking maternity leave, and having more than one child increased the likelihood of this.

The most common negative factor associated with family planning was long work hours and heavy workload (66.6%),

These findings suggest there are systemic changes needed not only in the healthcare setting but in society as a whole around women in the workplace and their choices of childbearing, say the authors.

The study was published online in JAMA Network Open and led by Anna Lee MD, MPH, from the department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston. 

In an invited commentary, Mona Saleh, MD, and Stephanie Blank, MD, from the department of obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai in New York, suggest that cultural changes are needed that go beyond women in medicine.

“These cultural values are so deeply pervasive (one could also say invasive) that they affect even these most educated and wealthy professional women, such as those who participated in this survey,” the editorialists write.

“[The researchers] advocate for early education on assisted reproductive technology (ART) risks, benefits, and success rates, but this is not getting at the underlying issue: Pregnancy discrimination and unfair distribution of childbearing responsibilities are a reflection of a larger problematic culture rather than an issue specific to women in medicine,” they add.
 

Survey details

The survey comprised a novel 39-item questionnaire distributed to 1,004 U.S. female oncologists from May 7 to June 30, 2020, via email and social media channels.

Most respondents (84.4%) were married, and 71% were currently working full-time.

About one-third (35%) worked in radiation oncology, another third (34.3%) in medical oncology, 18.4% in surgical oncology, and 9.1% in pediatric oncology.

A total of 768 respondents (76.5%) had children, and of these, 415 (41.3%) first gave birth during postgraduate training and 275 (27.4%) gave birth in years 1-5 as an attending physician.

Of all respondents who had been pregnant, approximately two-thirds (65.7%) had some type of pregnancy complication. About one-third of respondents (31.7%) reported having experienced a miscarriage after a confirmed pregnancy; of those, 61.6% reported one miscarriage, while the remainder had two or more miscarriages (38.4%).

Approximately one-third (31.4%) of respondents reported difficulty with infertility that required fertility counseling and/or treatment.

The questionnaire also asked about assisted reproductive technology, and 164 participants (16.3%) reported the use of fertility medications, and 53 (5.3%) reported cryopreservation of eggs. Nearly 13% reported the use of intrauterine insemination and 13.2% reported the use of in vivo fertilization. Among those who experienced fertility concerns, 36.6% (232 of 634) reported facing financial burdens because of fertility or pregnancy that was in some way associated with their career choice.

When asked on the survey if fertility preservation should be discussed with women during medical school and/or residency, 65.7% of respondents stated that it should.

However, the editorialists suggest that “encouraging formal and directed education regarding the infertility risks specifically toward female physicians (which Lee et al. recommend) could be perceived as a blanket recommendation that it is best for women in medicine to delay childbearing and pursue ART.”

“Medical schools and residency and fellowship training programs should instead focus their energy on creating a framework and culture that normalizes conception during these points in training while also subsidizing and supporting trainees and physicians who prefer to use ART and delay fertility until after training,” they suggest.

The editorialists also emphasized that women may choose to become pregnant at any point during the years that it takes to go from being a medical student to resident/fellow to attending physician, and they should be supported by their workplace on their decisions.

The study was funded by grants from National Institutes of Health/National Cancer Institute Cancer Center.

Dr. Lee and coauthors reported no relevant financial relationships. Dr. Blank reported receiving grants from AstraZeneca, Aravive, Akesobio, GlaxoSmithKline, Merck, and Seattle Genetics outside the submitted work. Dr. Saleh reports no relevant financial relationships.

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

The two national emergency declarations dealing with the COVID-19 pandemic will end May 11, President Joe Biden said on Jan. 30.

Doing so will have many effects, including the end of free vaccines and health services to fight the pandemic. The public health emergency has been renewed every 90 days since it was declared by the Trump administration in January 2020.

The declaration allowed major changes throughout the health care system to deal with the pandemic, including the free distribution of vaccines, testing, and treatments. In addition, telehealth services were expanded, and Medicaid and the Children’s Health Insurance Program were extended to millions more Americans.

Biden said the COVID-19 national emergency is set to expire March 1 while the declared public health emergency would currently expire on April 11. The president said both will be extended to end May 11.

There were nearly 300,000 newly reported COVID-19 cases in the United States for the week ending Jan. 25, according to CDC data, as well as more than 3,750 deaths.

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

The two national emergency declarations dealing with the COVID-19 pandemic will end May 11, President Joe Biden said on Jan. 30.

Doing so will have many effects, including the end of free vaccines and health services to fight the pandemic. The public health emergency has been renewed every 90 days since it was declared by the Trump administration in January 2020.

The declaration allowed major changes throughout the health care system to deal with the pandemic, including the free distribution of vaccines, testing, and treatments. In addition, telehealth services were expanded, and Medicaid and the Children’s Health Insurance Program were extended to millions more Americans.

Biden said the COVID-19 national emergency is set to expire March 1 while the declared public health emergency would currently expire on April 11. The president said both will be extended to end May 11.

There were nearly 300,000 newly reported COVID-19 cases in the United States for the week ending Jan. 25, according to CDC data, as well as more than 3,750 deaths.

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

The two national emergency declarations dealing with the COVID-19 pandemic will end May 11, President Joe Biden said on Jan. 30.

Doing so will have many effects, including the end of free vaccines and health services to fight the pandemic. The public health emergency has been renewed every 90 days since it was declared by the Trump administration in January 2020.

The declaration allowed major changes throughout the health care system to deal with the pandemic, including the free distribution of vaccines, testing, and treatments. In addition, telehealth services were expanded, and Medicaid and the Children’s Health Insurance Program were extended to millions more Americans.

Biden said the COVID-19 national emergency is set to expire March 1 while the declared public health emergency would currently expire on April 11. The president said both will be extended to end May 11.

There were nearly 300,000 newly reported COVID-19 cases in the United States for the week ending Jan. 25, according to CDC data, as well as more than 3,750 deaths.

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

Newly released figures showing a rise in the number of men with advanced prostate cancer have laid bare long-simmering resentment among patient advocates who feel the nation’s leading cancer group has largely ignored their concerns for years.

The American Cancer Society on Jan. 13 revealed what it called “alarming” news about prostate cancer: After 2 decades of decline, the number of men diagnosed with the disease in the United States rose by 15% from 2014 to 2019.

“Most concerning,” according to the group’s CEO Karen Knudsen, PhD, MBA, is that the increase is being driven by diagnoses of advanced disease.

“Since 2011, the diagnosis of advanced-stage (regional- or distant-stage) prostate cancer has increased by 4%-5% annually and the proportion of men diagnosed with distant-stage disease has doubled,” said Dr. Knudsen at a press conference concerning the figures. “These findings underscore the importance of understanding and reducing this trend.”

The increase, which works out to be an additional 99,000 cases of prostate cancer, did not take the ACS by surprise; the group has been predicting a jump in diagnoses of the disease, which is the most common cancer in men after skin cancer, and the second most common cause of cancer death for that group.

The ACS announced a new action plan, “Improving Mortality from Prostate Cancer Together” – or IMPACT – to address the rise, especially in Black men, and to curb the increasing rate of advanced, difficult-to-treat cases.

“We must address these shifts in prostate cancer, especially in the Black community, since the incidence of prostate cancer in Black men is 70% higher than in White men and prostate cancer mortality rates in Black men are approximately two to four times higher than those in every other racial and ethnic group,” William Dahut, MD, PhD, chief scientific officer for the ACS, said at the press conference.

A study published in JAMA Network Open challenged that claim, finding that, after controlling for socioeconomic factors, race does not appear to be a significant predictor of mortality for prostate cancer.

Dr. Dahut said in an interview that IMPACT “is still [in the] early days for this initiative and more details will be coming out soon.”

Charles Ryan, MD, CEO of the Prostate Cancer Foundation, the world’s largest prostate cancer research charity, called IMPACT “extremely important work. Highlighting the disparities can only serve to benefit all men with prostate cancer, especially Black men.”
 

Bold action ... or passivity?

Overall cancer mortality has dropped 33% since 1991, averting an estimated 3.8 million deaths, according to ACS. But the story for prostate cancer is different.

The society and advocates had warned as recently as 2 years ago that prostate cancer was poised to rise again, especially advanced cases that may be too late to treat.

Leaders in the prostate cancer advocacy community praised the ACS plan for IMPACT, but some expressed frustration over what they said was ACS’ passivity in the face of long-anticipated increases in cases of the disease.

“I think prostate cancer was not high on their agenda,” said Rick Davis, founder of AnCan, which offers several support groups for patients with prostate cancer.  “It’s good to see ACS get back into the prostate cancer game.”

Mr. Davis and patient advocate Darryl Mitteldorf, LCSW, founder of Malecare, another prostate support organization, said ACS dropped patient services for prostate cancer patients a decade ago and has not been a vocal supporter of screening for levels of prostate-specific antigen (PSA) to detect prostate cancer early.

“Early detection is supposed to be their goal,” Mr. Davis said.

In 2012, the U.S. Preventive Services Task Force recommended against PSA screening, giving it a D-rating. The move prompted attacks on the task force from most advocates and many urologists.

Following this criticism, the task force recommended shared decision-making between patient and doctor, while giving PSA screening a C-rating. Now, the ACS recommends men in general at age 50 discuss prostate cancer screening with their doctor and that Black men do the same at age 45.

Mr. Mitteldorf said ACS “owes prostate cancer patients an explanation and analysis of its response to the USPTF’s downgrade of PSA testing and how that response might be related to death and instance rates.”

Mr. Mitteldorf added that male patients lost key support from ACS when the group dismantled its Man to Man group for prostate cancer patients and its Brother to Brother group for Blacks in particular.

Dr. Dahut said Man to Man “sunsetted” and was turned over to any local organization that chose to offer it. He said longtime staff didn’t have “a lot of information about [the demise of] Brother to Brother.”

For Mr. Davis, those smaller cuts add up to a much larger insult.

“Today, in 2023, ACS continues to poke a finger in the eyes of prostate cancer patients,” he said. “Since 2010, they have not given us any respect. ACS dumped its support.”

He pointed to the group’s funding priorities, noting that outlays for prostate cancer have consistently lagged behind those for breast cancer.

The ACS spent $25.3 million on breast cancer research and $6.7 million for prostate cancer in 2018, and in 2023 will designate $126.5 for breast cancer research and $43.9 million for prostate cancer.

ACS has earmarked $62 million this year for lung cancer programs and $61 million for colorectal cancer.

“Parity between breast cancer and prostate cancer would be a good start in sizing the IMPACT program,” Mr. Davis said. “After all, breast cancer and prostate cancer are hardly different in numbers today.”

Dr. Dahut denied any gender bias in research funding. He said the group makes funding decisions “based on finding the most impactful science regardless of tumor type. Our mission includes funding every cancer, every day; thus, we generally do not go into our funding cycle with any set-asides for a particular cancer.”

Mr. Davis also said the ACS data suggest the growing number of prostate cancer cases is even worse than the group has said. Although the society cites a 3% annual increase in prostate cancer diagnoses from 2014 to 2019, since 2019 the annual increase is a much more dramatic 16%. Meanwhile, the number of new cases of the disease is projected to rise from 175,000 per year in 2019 to 288,000 this year.

Dr. Dahut said the society used the 2014-2019 time frame for technical reasons, separating confirmed cases in the earlier period from estimated cases in recent years.

“We discourage comparing projected cases over time because these cases are model-based and subject to fluctuations,” Dr. Dahut said.

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

Newly released figures showing a rise in the number of men with advanced prostate cancer have laid bare long-simmering resentment among patient advocates who feel the nation’s leading cancer group has largely ignored their concerns for years.

The American Cancer Society on Jan. 13 revealed what it called “alarming” news about prostate cancer: After 2 decades of decline, the number of men diagnosed with the disease in the United States rose by 15% from 2014 to 2019.

“Most concerning,” according to the group’s CEO Karen Knudsen, PhD, MBA, is that the increase is being driven by diagnoses of advanced disease.

“Since 2011, the diagnosis of advanced-stage (regional- or distant-stage) prostate cancer has increased by 4%-5% annually and the proportion of men diagnosed with distant-stage disease has doubled,” said Dr. Knudsen at a press conference concerning the figures. “These findings underscore the importance of understanding and reducing this trend.”

The increase, which works out to be an additional 99,000 cases of prostate cancer, did not take the ACS by surprise; the group has been predicting a jump in diagnoses of the disease, which is the most common cancer in men after skin cancer, and the second most common cause of cancer death for that group.

The ACS announced a new action plan, “Improving Mortality from Prostate Cancer Together” – or IMPACT – to address the rise, especially in Black men, and to curb the increasing rate of advanced, difficult-to-treat cases.

“We must address these shifts in prostate cancer, especially in the Black community, since the incidence of prostate cancer in Black men is 70% higher than in White men and prostate cancer mortality rates in Black men are approximately two to four times higher than those in every other racial and ethnic group,” William Dahut, MD, PhD, chief scientific officer for the ACS, said at the press conference.

A study published in JAMA Network Open challenged that claim, finding that, after controlling for socioeconomic factors, race does not appear to be a significant predictor of mortality for prostate cancer.

Dr. Dahut said in an interview that IMPACT “is still [in the] early days for this initiative and more details will be coming out soon.”

Charles Ryan, MD, CEO of the Prostate Cancer Foundation, the world’s largest prostate cancer research charity, called IMPACT “extremely important work. Highlighting the disparities can only serve to benefit all men with prostate cancer, especially Black men.”
 

Bold action ... or passivity?

Overall cancer mortality has dropped 33% since 1991, averting an estimated 3.8 million deaths, according to ACS. But the story for prostate cancer is different.

The society and advocates had warned as recently as 2 years ago that prostate cancer was poised to rise again, especially advanced cases that may be too late to treat.

Leaders in the prostate cancer advocacy community praised the ACS plan for IMPACT, but some expressed frustration over what they said was ACS’ passivity in the face of long-anticipated increases in cases of the disease.

“I think prostate cancer was not high on their agenda,” said Rick Davis, founder of AnCan, which offers several support groups for patients with prostate cancer.  “It’s good to see ACS get back into the prostate cancer game.”

Mr. Davis and patient advocate Darryl Mitteldorf, LCSW, founder of Malecare, another prostate support organization, said ACS dropped patient services for prostate cancer patients a decade ago and has not been a vocal supporter of screening for levels of prostate-specific antigen (PSA) to detect prostate cancer early.

“Early detection is supposed to be their goal,” Mr. Davis said.

In 2012, the U.S. Preventive Services Task Force recommended against PSA screening, giving it a D-rating. The move prompted attacks on the task force from most advocates and many urologists.

Following this criticism, the task force recommended shared decision-making between patient and doctor, while giving PSA screening a C-rating. Now, the ACS recommends men in general at age 50 discuss prostate cancer screening with their doctor and that Black men do the same at age 45.

Mr. Mitteldorf said ACS “owes prostate cancer patients an explanation and analysis of its response to the USPTF’s downgrade of PSA testing and how that response might be related to death and instance rates.”

Mr. Mitteldorf added that male patients lost key support from ACS when the group dismantled its Man to Man group for prostate cancer patients and its Brother to Brother group for Blacks in particular.

Dr. Dahut said Man to Man “sunsetted” and was turned over to any local organization that chose to offer it. He said longtime staff didn’t have “a lot of information about [the demise of] Brother to Brother.”

For Mr. Davis, those smaller cuts add up to a much larger insult.

“Today, in 2023, ACS continues to poke a finger in the eyes of prostate cancer patients,” he said. “Since 2010, they have not given us any respect. ACS dumped its support.”

He pointed to the group’s funding priorities, noting that outlays for prostate cancer have consistently lagged behind those for breast cancer.

The ACS spent $25.3 million on breast cancer research and $6.7 million for prostate cancer in 2018, and in 2023 will designate $126.5 for breast cancer research and $43.9 million for prostate cancer.

ACS has earmarked $62 million this year for lung cancer programs and $61 million for colorectal cancer.

“Parity between breast cancer and prostate cancer would be a good start in sizing the IMPACT program,” Mr. Davis said. “After all, breast cancer and prostate cancer are hardly different in numbers today.”

Dr. Dahut denied any gender bias in research funding. He said the group makes funding decisions “based on finding the most impactful science regardless of tumor type. Our mission includes funding every cancer, every day; thus, we generally do not go into our funding cycle with any set-asides for a particular cancer.”

Mr. Davis also said the ACS data suggest the growing number of prostate cancer cases is even worse than the group has said. Although the society cites a 3% annual increase in prostate cancer diagnoses from 2014 to 2019, since 2019 the annual increase is a much more dramatic 16%. Meanwhile, the number of new cases of the disease is projected to rise from 175,000 per year in 2019 to 288,000 this year.

Dr. Dahut said the society used the 2014-2019 time frame for technical reasons, separating confirmed cases in the earlier period from estimated cases in recent years.

“We discourage comparing projected cases over time because these cases are model-based and subject to fluctuations,” Dr. Dahut said.

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

Newly released figures showing a rise in the number of men with advanced prostate cancer have laid bare long-simmering resentment among patient advocates who feel the nation’s leading cancer group has largely ignored their concerns for years.

The American Cancer Society on Jan. 13 revealed what it called “alarming” news about prostate cancer: After 2 decades of decline, the number of men diagnosed with the disease in the United States rose by 15% from 2014 to 2019.

“Most concerning,” according to the group’s CEO Karen Knudsen, PhD, MBA, is that the increase is being driven by diagnoses of advanced disease.

“Since 2011, the diagnosis of advanced-stage (regional- or distant-stage) prostate cancer has increased by 4%-5% annually and the proportion of men diagnosed with distant-stage disease has doubled,” said Dr. Knudsen at a press conference concerning the figures. “These findings underscore the importance of understanding and reducing this trend.”

The increase, which works out to be an additional 99,000 cases of prostate cancer, did not take the ACS by surprise; the group has been predicting a jump in diagnoses of the disease, which is the most common cancer in men after skin cancer, and the second most common cause of cancer death for that group.

The ACS announced a new action plan, “Improving Mortality from Prostate Cancer Together” – or IMPACT – to address the rise, especially in Black men, and to curb the increasing rate of advanced, difficult-to-treat cases.

“We must address these shifts in prostate cancer, especially in the Black community, since the incidence of prostate cancer in Black men is 70% higher than in White men and prostate cancer mortality rates in Black men are approximately two to four times higher than those in every other racial and ethnic group,” William Dahut, MD, PhD, chief scientific officer for the ACS, said at the press conference.

A study published in JAMA Network Open challenged that claim, finding that, after controlling for socioeconomic factors, race does not appear to be a significant predictor of mortality for prostate cancer.

Dr. Dahut said in an interview that IMPACT “is still [in the] early days for this initiative and more details will be coming out soon.”

Charles Ryan, MD, CEO of the Prostate Cancer Foundation, the world’s largest prostate cancer research charity, called IMPACT “extremely important work. Highlighting the disparities can only serve to benefit all men with prostate cancer, especially Black men.”
 

Bold action ... or passivity?

Overall cancer mortality has dropped 33% since 1991, averting an estimated 3.8 million deaths, according to ACS. But the story for prostate cancer is different.

The society and advocates had warned as recently as 2 years ago that prostate cancer was poised to rise again, especially advanced cases that may be too late to treat.

Leaders in the prostate cancer advocacy community praised the ACS plan for IMPACT, but some expressed frustration over what they said was ACS’ passivity in the face of long-anticipated increases in cases of the disease.

“I think prostate cancer was not high on their agenda,” said Rick Davis, founder of AnCan, which offers several support groups for patients with prostate cancer.  “It’s good to see ACS get back into the prostate cancer game.”

Mr. Davis and patient advocate Darryl Mitteldorf, LCSW, founder of Malecare, another prostate support organization, said ACS dropped patient services for prostate cancer patients a decade ago and has not been a vocal supporter of screening for levels of prostate-specific antigen (PSA) to detect prostate cancer early.

“Early detection is supposed to be their goal,” Mr. Davis said.

In 2012, the U.S. Preventive Services Task Force recommended against PSA screening, giving it a D-rating. The move prompted attacks on the task force from most advocates and many urologists.

Following this criticism, the task force recommended shared decision-making between patient and doctor, while giving PSA screening a C-rating. Now, the ACS recommends men in general at age 50 discuss prostate cancer screening with their doctor and that Black men do the same at age 45.

Mr. Mitteldorf said ACS “owes prostate cancer patients an explanation and analysis of its response to the USPTF’s downgrade of PSA testing and how that response might be related to death and instance rates.”

Mr. Mitteldorf added that male patients lost key support from ACS when the group dismantled its Man to Man group for prostate cancer patients and its Brother to Brother group for Blacks in particular.

Dr. Dahut said Man to Man “sunsetted” and was turned over to any local organization that chose to offer it. He said longtime staff didn’t have “a lot of information about [the demise of] Brother to Brother.”

For Mr. Davis, those smaller cuts add up to a much larger insult.

“Today, in 2023, ACS continues to poke a finger in the eyes of prostate cancer patients,” he said. “Since 2010, they have not given us any respect. ACS dumped its support.”

He pointed to the group’s funding priorities, noting that outlays for prostate cancer have consistently lagged behind those for breast cancer.

The ACS spent $25.3 million on breast cancer research and $6.7 million for prostate cancer in 2018, and in 2023 will designate $126.5 for breast cancer research and $43.9 million for prostate cancer.

ACS has earmarked $62 million this year for lung cancer programs and $61 million for colorectal cancer.

“Parity between breast cancer and prostate cancer would be a good start in sizing the IMPACT program,” Mr. Davis said. “After all, breast cancer and prostate cancer are hardly different in numbers today.”

Dr. Dahut denied any gender bias in research funding. He said the group makes funding decisions “based on finding the most impactful science regardless of tumor type. Our mission includes funding every cancer, every day; thus, we generally do not go into our funding cycle with any set-asides for a particular cancer.”

Mr. Davis also said the ACS data suggest the growing number of prostate cancer cases is even worse than the group has said. Although the society cites a 3% annual increase in prostate cancer diagnoses from 2014 to 2019, since 2019 the annual increase is a much more dramatic 16%. Meanwhile, the number of new cases of the disease is projected to rise from 175,000 per year in 2019 to 288,000 this year.

Dr. Dahut said the society used the 2014-2019 time frame for technical reasons, separating confirmed cases in the earlier period from estimated cases in recent years.

“We discourage comparing projected cases over time because these cases are model-based and subject to fluctuations,” Dr. Dahut said.

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

The Food and Drug Administration has granted accelerated approval to pirtobrutinib (Jaypirca) for relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton’s tyrosine kinase inhibitor.

Pirtobrutinib is the first and only noncovalent Bruton’s tyrosine kinase inhibitor approved for use in this MCL setting, manufacturer Eli Lilly noted in a press release.

“The approval of Jaypirca represents an important advance for patients with relapsed or refractory MCL, who currently have limited options and historically have had a poor prognosis following discontinuation of treatment with a covalent Bruton’s tyrosine kinase inhibitor,” senior author Michael Wang, MD, University of Texas MD Anderson Cancer Center, Houston, said in the release.

The approval was based on efficacy demonstrated in the open-label, single-arm, phase 1/2 BRUIN trial – a multicenter study assessing 200 mg once-daily oral pirtobrutinib monotherapy in 120 patients with MCL who had previously received a Bruton’s tyrosine kinase inhibitor, most often ibrutinib (Imbruvica, 67%) acalabrutinib (Calquence, 30%) and zanubrutinib (Brukinsa, 8%). Pirtobrutinib was continued until disease progression or unacceptable toxicity.

Study participants had a median of three prior lines of therapy, and 83% discontinued their last Bruton’s tyrosine kinase inhibitor because of refractory or progressive disease.

The overall response rate in pirtobrutinib-treated patients was 50% with a complete response rate of 13%. Estimated median duration of response was 8.3 months, and the estimated duration of response at 6 months occurred in nearly two-thirds of patients.

Adverse reactions that occurred in at least 15% of patients included fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included decreased neutrophil counts, lymphocyte counts, and platelet counts.

Prescribing information for pirtobrutinib includes warnings and precautions for infections, hemorrhage, cytopenias, atrial fibrillation and flutter, and second primary malignancies, noted the FDA, which granted priority review, fast track designation, and orphan drug designation for the application submitted by Eli Lilly.

“Jaypirca can reestablish Bruton’s tyrosine kinase inhibition in MCL patients previously treated with a covalent Bruton’s tyrosine kinase inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) and extend the benefit of targeting the Bruton’s tyrosine kinase pathway,” according to Eli Lilly’s release.

Dr. Wang added that the agent “has the potential to meaningfully impact the treatment paradigm for relapsed and refractory MCL patients.”

Meghan Gutierrez, CEO at the Lymphoma Research Foundation, also noted that “the approval of Jaypirca brings a new treatment option and, along with that, new hope for people with relapsed or refractory MCL.”

The drug is expected to be available in the United States in the coming weeks, and the confirmatory phase 3 BRUIN trial is currently enrolling patients, Eli Lilly announced. The company also indicated the list price would be $21,000 for a 30-day supply of the 200-mg dose.

Serious adverse events believed to be associated with the use of pirtobrutinib or any medicine or device should be reported to the FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

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

The Food and Drug Administration has granted accelerated approval to pirtobrutinib (Jaypirca) for relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton’s tyrosine kinase inhibitor.

Pirtobrutinib is the first and only noncovalent Bruton’s tyrosine kinase inhibitor approved for use in this MCL setting, manufacturer Eli Lilly noted in a press release.

“The approval of Jaypirca represents an important advance for patients with relapsed or refractory MCL, who currently have limited options and historically have had a poor prognosis following discontinuation of treatment with a covalent Bruton’s tyrosine kinase inhibitor,” senior author Michael Wang, MD, University of Texas MD Anderson Cancer Center, Houston, said in the release.

The approval was based on efficacy demonstrated in the open-label, single-arm, phase 1/2 BRUIN trial – a multicenter study assessing 200 mg once-daily oral pirtobrutinib monotherapy in 120 patients with MCL who had previously received a Bruton’s tyrosine kinase inhibitor, most often ibrutinib (Imbruvica, 67%) acalabrutinib (Calquence, 30%) and zanubrutinib (Brukinsa, 8%). Pirtobrutinib was continued until disease progression or unacceptable toxicity.

Study participants had a median of three prior lines of therapy, and 83% discontinued their last Bruton’s tyrosine kinase inhibitor because of refractory or progressive disease.

The overall response rate in pirtobrutinib-treated patients was 50% with a complete response rate of 13%. Estimated median duration of response was 8.3 months, and the estimated duration of response at 6 months occurred in nearly two-thirds of patients.

Adverse reactions that occurred in at least 15% of patients included fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included decreased neutrophil counts, lymphocyte counts, and platelet counts.

Prescribing information for pirtobrutinib includes warnings and precautions for infections, hemorrhage, cytopenias, atrial fibrillation and flutter, and second primary malignancies, noted the FDA, which granted priority review, fast track designation, and orphan drug designation for the application submitted by Eli Lilly.

“Jaypirca can reestablish Bruton’s tyrosine kinase inhibition in MCL patients previously treated with a covalent Bruton’s tyrosine kinase inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) and extend the benefit of targeting the Bruton’s tyrosine kinase pathway,” according to Eli Lilly’s release.

Dr. Wang added that the agent “has the potential to meaningfully impact the treatment paradigm for relapsed and refractory MCL patients.”

Meghan Gutierrez, CEO at the Lymphoma Research Foundation, also noted that “the approval of Jaypirca brings a new treatment option and, along with that, new hope for people with relapsed or refractory MCL.”

The drug is expected to be available in the United States in the coming weeks, and the confirmatory phase 3 BRUIN trial is currently enrolling patients, Eli Lilly announced. The company also indicated the list price would be $21,000 for a 30-day supply of the 200-mg dose.

Serious adverse events believed to be associated with the use of pirtobrutinib or any medicine or device should be reported to the FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

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

The Food and Drug Administration has granted accelerated approval to pirtobrutinib (Jaypirca) for relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton’s tyrosine kinase inhibitor.

Pirtobrutinib is the first and only noncovalent Bruton’s tyrosine kinase inhibitor approved for use in this MCL setting, manufacturer Eli Lilly noted in a press release.

“The approval of Jaypirca represents an important advance for patients with relapsed or refractory MCL, who currently have limited options and historically have had a poor prognosis following discontinuation of treatment with a covalent Bruton’s tyrosine kinase inhibitor,” senior author Michael Wang, MD, University of Texas MD Anderson Cancer Center, Houston, said in the release.

The approval was based on efficacy demonstrated in the open-label, single-arm, phase 1/2 BRUIN trial – a multicenter study assessing 200 mg once-daily oral pirtobrutinib monotherapy in 120 patients with MCL who had previously received a Bruton’s tyrosine kinase inhibitor, most often ibrutinib (Imbruvica, 67%) acalabrutinib (Calquence, 30%) and zanubrutinib (Brukinsa, 8%). Pirtobrutinib was continued until disease progression or unacceptable toxicity.

Study participants had a median of three prior lines of therapy, and 83% discontinued their last Bruton’s tyrosine kinase inhibitor because of refractory or progressive disease.

The overall response rate in pirtobrutinib-treated patients was 50% with a complete response rate of 13%. Estimated median duration of response was 8.3 months, and the estimated duration of response at 6 months occurred in nearly two-thirds of patients.

Adverse reactions that occurred in at least 15% of patients included fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included decreased neutrophil counts, lymphocyte counts, and platelet counts.

Prescribing information for pirtobrutinib includes warnings and precautions for infections, hemorrhage, cytopenias, atrial fibrillation and flutter, and second primary malignancies, noted the FDA, which granted priority review, fast track designation, and orphan drug designation for the application submitted by Eli Lilly.

“Jaypirca can reestablish Bruton’s tyrosine kinase inhibition in MCL patients previously treated with a covalent Bruton’s tyrosine kinase inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) and extend the benefit of targeting the Bruton’s tyrosine kinase pathway,” according to Eli Lilly’s release.

Dr. Wang added that the agent “has the potential to meaningfully impact the treatment paradigm for relapsed and refractory MCL patients.”

Meghan Gutierrez, CEO at the Lymphoma Research Foundation, also noted that “the approval of Jaypirca brings a new treatment option and, along with that, new hope for people with relapsed or refractory MCL.”

The drug is expected to be available in the United States in the coming weeks, and the confirmatory phase 3 BRUIN trial is currently enrolling patients, Eli Lilly announced. The company also indicated the list price would be $21,000 for a 30-day supply of the 200-mg dose.

Serious adverse events believed to be associated with the use of pirtobrutinib or any medicine or device should be reported to the FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

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

The risk of health harms from alcohol is low for people who consume two standard drinks or fewer per week, but it’s higher with greater consumption, according to new guidance from the Canadian Centre on Substance Use and Addiction.

“Drinking less is better,” says the guidance, which replaces Canada’s 2011 Low-Risk Drinking Guidelines (LRDGs).

Developed in consultation with an executive committee from federal, provincial, and territorial governments; national organizations; three scientific expert panels; and an internal evidence review working group, the guidance presents the following findings:

• Consuming no drinks per week has benefits, such as better health and better sleep, and it’s the only safe option during pregnancy.
• Consuming one or two standard drinks weekly will likely not have alcohol-related consequences.
• Three to six drinks raise the risk of developing breast, colon, and other cancers.
• Seven or more increase the risk of heart disease or stroke.
• Each additional drink “radically increases” the risk of these health consequences.

“Alcohol is more harmful than was previously thought and is a key component of the health of your patients,” Adam Sherk, PhD, a scientist at the Canadian Institute for Substance Use Research at the University of Victoria (B.C.), and a member of the scientific expert panel that contributed to the guidance, said in an interview. “Display and discuss the new guidance with your patients with the main message that drinking less is better.”

Peter Butt, MD, a clinical associate professor at the University of Saskatchewan, Saskatoon, and cochair of the guidance project, said in an interview: “The World Health Organization has identified over 200 ICD-coded conditions associated with alcohol use. This creates many opportunities to inquire into quantity and frequency of alcohol use, relate it to the patient’s health and well-being, and provide advice on reduction.”

“Canada’s Guidance on Alcohol and Health: Final Report” and a related infographic were published online Jan. 17.
 

Continuum of risk

The impetus for the new guidance came from the fact that “our 2011 LRDGs were no longer current, and there was emerging evidence that people drinking within those levels were coming to harm,” said Dr. Butt.

That evidence indicates that alcohol causes at least seven types of cancer, mostly of the breast or colon; is a risk factor for most types of heart disease; and is a main cause of liver disease. Evidence also indicates that avoiding drinking to the point of intoxication will reduce people’s risk of perpetrating alcohol-related violence.

Responding to the need to accurately quantify the risk, the guidance defines a “standard” drink as 12 oz of beer, cooler, or cider (5% alcohol); 5 oz of wine (12% alcohol); and 1.5 oz of spirits such as whiskey, vodka, or gin (40% alcohol).

Using different mortality risk thresholds, the project’s experts developed the following continuum of risk:

• Low for individuals who consume two standard drinks or fewer per week
• Moderate for those who consume from three to six standard drinks per week
• Increasingly high for those who consume seven standard drinks or more per week

The guidance makes the following observations:

• Consuming more than two standard drinks per drinking occasion is associated with an increased risk of harms to self and others, including injuries and violence.
• When pregnant or trying to get pregnant, no amount of alcohol is safe.
• When breastfeeding, not drinking is safest.
• Above the upper limit of the moderate risk zone, health risks increase more steeply for females than males.
• Far more injuries, violence, and deaths result from men’s alcohol use, especially for per occasion drinking, than from women’s alcohol use.
• Young people should delay alcohol use for as long as possible.
• Individuals should not start to use alcohol or increase their alcohol use for health benefits.
• Any reduction in alcohol use is beneficial.

Other national guidelines

“Countries that haven’t updated their alcohol use guidelines recently should do so, as the evidence regarding alcohol and health has advanced considerably in the past 10 years,” said Dr. Sherk. He acknowledged that “any time health guidance changes substantially, it’s reasonable to expect a period of readjustment.”

“Some will be resistant,” Dr. Butt agreed. “Some professionals will need more education than others on the health effects of alcohol. Some patients will also be more invested in drinking than others. The harm-reduction, risk-zone approach should assist in the process of engaging patients and helping them reduce over time.

“Just as we benefited from the updates done in the United Kingdom, France, and especially Australia, so also researchers elsewhere will critique our work and our approach and make their own decisions on how best to communicate with their public,” Dr. Butt said. He noted that Canada’s contributions regarding the association between alcohol and violence, as well as their sex/gender approach to the evidence, “may influence the next country’s review.”

Commenting on whether the United States should consider changing its guidance, Timothy Brennan, MD, MPH, chief of clinical services for the Addiction Institute of Mount Sinai Health System in New York, said in an interview, “A lot of people will be surprised at the recommended limits on alcohol. Most think that they can have one or two glasses of alcohol per day and not have any increased risk to their health. I think the Canadians deserve credit for putting themselves out there.”

Dr. Brennan said there will “certainly be pushback by the drinking lobby, which is very strong both in the U.S. and in Canada.” In fact, the national trade group Beer Canada was recently quoted as stating that it still supports the 2011 guidelines and that the updating process lacked full transparency and expert technical peer review.

Nevertheless, Dr. Brennan said, “it’s overwhelmingly clear that alcohol affects a ton of different parts of our body, so limiting the amount of alcohol we take in is always going to be a good thing. The Canadian graphic is great because it color-codes the risk. I recommend that clinicians put it up in their offices and begin quantifying the units of alcohol that are going into a patient’s body each day.”

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

The risk of health harms from alcohol is low for people who consume two standard drinks or fewer per week, but it’s higher with greater consumption, according to new guidance from the Canadian Centre on Substance Use and Addiction.

“Drinking less is better,” says the guidance, which replaces Canada’s 2011 Low-Risk Drinking Guidelines (LRDGs).

Developed in consultation with an executive committee from federal, provincial, and territorial governments; national organizations; three scientific expert panels; and an internal evidence review working group, the guidance presents the following findings:

• Consuming no drinks per week has benefits, such as better health and better sleep, and it’s the only safe option during pregnancy.
• Consuming one or two standard drinks weekly will likely not have alcohol-related consequences.
• Three to six drinks raise the risk of developing breast, colon, and other cancers.
• Seven or more increase the risk of heart disease or stroke.
• Each additional drink “radically increases” the risk of these health consequences.

“Alcohol is more harmful than was previously thought and is a key component of the health of your patients,” Adam Sherk, PhD, a scientist at the Canadian Institute for Substance Use Research at the University of Victoria (B.C.), and a member of the scientific expert panel that contributed to the guidance, said in an interview. “Display and discuss the new guidance with your patients with the main message that drinking less is better.”

Peter Butt, MD, a clinical associate professor at the University of Saskatchewan, Saskatoon, and cochair of the guidance project, said in an interview: “The World Health Organization has identified over 200 ICD-coded conditions associated with alcohol use. This creates many opportunities to inquire into quantity and frequency of alcohol use, relate it to the patient’s health and well-being, and provide advice on reduction.”

“Canada’s Guidance on Alcohol and Health: Final Report” and a related infographic were published online Jan. 17.
 

Continuum of risk

The impetus for the new guidance came from the fact that “our 2011 LRDGs were no longer current, and there was emerging evidence that people drinking within those levels were coming to harm,” said Dr. Butt.

That evidence indicates that alcohol causes at least seven types of cancer, mostly of the breast or colon; is a risk factor for most types of heart disease; and is a main cause of liver disease. Evidence also indicates that avoiding drinking to the point of intoxication will reduce people’s risk of perpetrating alcohol-related violence.

Responding to the need to accurately quantify the risk, the guidance defines a “standard” drink as 12 oz of beer, cooler, or cider (5% alcohol); 5 oz of wine (12% alcohol); and 1.5 oz of spirits such as whiskey, vodka, or gin (40% alcohol).

Using different mortality risk thresholds, the project’s experts developed the following continuum of risk:

• Low for individuals who consume two standard drinks or fewer per week
• Moderate for those who consume from three to six standard drinks per week
• Increasingly high for those who consume seven standard drinks or more per week

The guidance makes the following observations:

• Consuming more than two standard drinks per drinking occasion is associated with an increased risk of harms to self and others, including injuries and violence.
• When pregnant or trying to get pregnant, no amount of alcohol is safe.
• When breastfeeding, not drinking is safest.
• Above the upper limit of the moderate risk zone, health risks increase more steeply for females than males.
• Far more injuries, violence, and deaths result from men’s alcohol use, especially for per occasion drinking, than from women’s alcohol use.
• Young people should delay alcohol use for as long as possible.
• Individuals should not start to use alcohol or increase their alcohol use for health benefits.
• Any reduction in alcohol use is beneficial.

Other national guidelines

“Countries that haven’t updated their alcohol use guidelines recently should do so, as the evidence regarding alcohol and health has advanced considerably in the past 10 years,” said Dr. Sherk. He acknowledged that “any time health guidance changes substantially, it’s reasonable to expect a period of readjustment.”

“Some will be resistant,” Dr. Butt agreed. “Some professionals will need more education than others on the health effects of alcohol. Some patients will also be more invested in drinking than others. The harm-reduction, risk-zone approach should assist in the process of engaging patients and helping them reduce over time.

“Just as we benefited from the updates done in the United Kingdom, France, and especially Australia, so also researchers elsewhere will critique our work and our approach and make their own decisions on how best to communicate with their public,” Dr. Butt said. He noted that Canada’s contributions regarding the association between alcohol and violence, as well as their sex/gender approach to the evidence, “may influence the next country’s review.”

Commenting on whether the United States should consider changing its guidance, Timothy Brennan, MD, MPH, chief of clinical services for the Addiction Institute of Mount Sinai Health System in New York, said in an interview, “A lot of people will be surprised at the recommended limits on alcohol. Most think that they can have one or two glasses of alcohol per day and not have any increased risk to their health. I think the Canadians deserve credit for putting themselves out there.”

Dr. Brennan said there will “certainly be pushback by the drinking lobby, which is very strong both in the U.S. and in Canada.” In fact, the national trade group Beer Canada was recently quoted as stating that it still supports the 2011 guidelines and that the updating process lacked full transparency and expert technical peer review.

Nevertheless, Dr. Brennan said, “it’s overwhelmingly clear that alcohol affects a ton of different parts of our body, so limiting the amount of alcohol we take in is always going to be a good thing. The Canadian graphic is great because it color-codes the risk. I recommend that clinicians put it up in their offices and begin quantifying the units of alcohol that are going into a patient’s body each day.”

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

The risk of health harms from alcohol is low for people who consume two standard drinks or fewer per week, but it’s higher with greater consumption, according to new guidance from the Canadian Centre on Substance Use and Addiction.

“Drinking less is better,” says the guidance, which replaces Canada’s 2011 Low-Risk Drinking Guidelines (LRDGs).

Developed in consultation with an executive committee from federal, provincial, and territorial governments; national organizations; three scientific expert panels; and an internal evidence review working group, the guidance presents the following findings:

• Consuming no drinks per week has benefits, such as better health and better sleep, and it’s the only safe option during pregnancy.
• Consuming one or two standard drinks weekly will likely not have alcohol-related consequences.
• Three to six drinks raise the risk of developing breast, colon, and other cancers.
• Seven or more increase the risk of heart disease or stroke.
• Each additional drink “radically increases” the risk of these health consequences.

“Alcohol is more harmful than was previously thought and is a key component of the health of your patients,” Adam Sherk, PhD, a scientist at the Canadian Institute for Substance Use Research at the University of Victoria (B.C.), and a member of the scientific expert panel that contributed to the guidance, said in an interview. “Display and discuss the new guidance with your patients with the main message that drinking less is better.”

Peter Butt, MD, a clinical associate professor at the University of Saskatchewan, Saskatoon, and cochair of the guidance project, said in an interview: “The World Health Organization has identified over 200 ICD-coded conditions associated with alcohol use. This creates many opportunities to inquire into quantity and frequency of alcohol use, relate it to the patient’s health and well-being, and provide advice on reduction.”

“Canada’s Guidance on Alcohol and Health: Final Report” and a related infographic were published online Jan. 17.
 

Continuum of risk

The impetus for the new guidance came from the fact that “our 2011 LRDGs were no longer current, and there was emerging evidence that people drinking within those levels were coming to harm,” said Dr. Butt.

That evidence indicates that alcohol causes at least seven types of cancer, mostly of the breast or colon; is a risk factor for most types of heart disease; and is a main cause of liver disease. Evidence also indicates that avoiding drinking to the point of intoxication will reduce people’s risk of perpetrating alcohol-related violence.

Responding to the need to accurately quantify the risk, the guidance defines a “standard” drink as 12 oz of beer, cooler, or cider (5% alcohol); 5 oz of wine (12% alcohol); and 1.5 oz of spirits such as whiskey, vodka, or gin (40% alcohol).

Using different mortality risk thresholds, the project’s experts developed the following continuum of risk:

• Low for individuals who consume two standard drinks or fewer per week
• Moderate for those who consume from three to six standard drinks per week
• Increasingly high for those who consume seven standard drinks or more per week

The guidance makes the following observations:

• Consuming more than two standard drinks per drinking occasion is associated with an increased risk of harms to self and others, including injuries and violence.
• When pregnant or trying to get pregnant, no amount of alcohol is safe.
• When breastfeeding, not drinking is safest.
• Above the upper limit of the moderate risk zone, health risks increase more steeply for females than males.
• Far more injuries, violence, and deaths result from men’s alcohol use, especially for per occasion drinking, than from women’s alcohol use.
• Young people should delay alcohol use for as long as possible.
• Individuals should not start to use alcohol or increase their alcohol use for health benefits.
• Any reduction in alcohol use is beneficial.

Other national guidelines

“Countries that haven’t updated their alcohol use guidelines recently should do so, as the evidence regarding alcohol and health has advanced considerably in the past 10 years,” said Dr. Sherk. He acknowledged that “any time health guidance changes substantially, it’s reasonable to expect a period of readjustment.”

“Some will be resistant,” Dr. Butt agreed. “Some professionals will need more education than others on the health effects of alcohol. Some patients will also be more invested in drinking than others. The harm-reduction, risk-zone approach should assist in the process of engaging patients and helping them reduce over time.

“Just as we benefited from the updates done in the United Kingdom, France, and especially Australia, so also researchers elsewhere will critique our work and our approach and make their own decisions on how best to communicate with their public,” Dr. Butt said. He noted that Canada’s contributions regarding the association between alcohol and violence, as well as their sex/gender approach to the evidence, “may influence the next country’s review.”

Commenting on whether the United States should consider changing its guidance, Timothy Brennan, MD, MPH, chief of clinical services for the Addiction Institute of Mount Sinai Health System in New York, said in an interview, “A lot of people will be surprised at the recommended limits on alcohol. Most think that they can have one or two glasses of alcohol per day and not have any increased risk to their health. I think the Canadians deserve credit for putting themselves out there.”

Dr. Brennan said there will “certainly be pushback by the drinking lobby, which is very strong both in the U.S. and in Canada.” In fact, the national trade group Beer Canada was recently quoted as stating that it still supports the 2011 guidelines and that the updating process lacked full transparency and expert technical peer review.

Nevertheless, Dr. Brennan said, “it’s overwhelmingly clear that alcohol affects a ton of different parts of our body, so limiting the amount of alcohol we take in is always going to be a good thing. The Canadian graphic is great because it color-codes the risk. I recommend that clinicians put it up in their offices and begin quantifying the units of alcohol that are going into a patient’s body each day.”

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

Systemic mastocytosis is widely underdiagnosed, and many more hematologic oncologists should be looking for it. This call to action was issued late in 2022 by Stanford (Calif.) Cancer Institute’s Jason Gotlib, MD, speaking at the Lymphoma, Leukemia & Myeloma Congress in New York.

Nationwide, approximately 1,000 adults are diagnosed with systemic mastocytosis annually. This rare disease is a myeloid neoplasm with a highly variable phenotypic expression, in which abnormal mast cells proliferate and infiltrate organs and tissues. It swings widely from a nonadvanced form, composed of indolent or smoldering disease, to advanced disease that progresses to leukemia in 6% of cases.

More than 80% of systemic mastocytosis is driven by the KIT D816V mutation. Along with a host of other rare KIT mutations, KIT D816V activates KIT-receptor tyrosine kinase to trigger mast cell proliferation.

Dr. Gotlib could not be contacted for an interview. However, there are many good reasons to identify patients with systemic mastocytosis, according to Attilio Orazi, MD, professor and chair of the department of pathology at Texas Tech University, El Paso. The chief reason is that the patient may be in grave peril.

“The degree of heterogeneity is amazing. ... There’s very indolent [disease], which is really not a big deal. And then you have a disease in which you’re dead in 3 months,” Dr. Orazi said. “So you run the gamut between an indolent, no-problem cutaneous disease to a very nasty systemic, aggressive leukemia-like neoplasm.”

Since 2001, the diagnosis of mastocytosis has been guided by the World Health Organization Classification of Tumours, or “Blue Book.” In 2022, Dr. Orazi along with 137 other senior experts, most of whom were involved in past editions of the Blue Book, published their own version: The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (the ICC 2022).

In September 2021, this group of specialists held a virtual/in-person advisory committee meeting at the University of Chicago to create the document. One factor in their decision to go it alone, Dr. Orazi said, was that WHO decided to proceed with the fifth edition of the Blue Book using its own internal editorial group without convening an advisory committee, despite repeated requests to do so.

ICC 2022 divides advanced systemic mastocytosis into three subtypes: aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL). Median survival is 3.5 years for patients with ASM, 2 years for those with SM-AHN and as low as 2 months for MCL.

The second key reason to increase awareness of mastocytosis among physicians, said Dr. Orazi, is that patients falling through the net are likely to be ambulatory, and their presentation can be “a little confusing.”

Patients with indolent disease are relatively straightforward to recognize, explained Dr. Orazi. Similarly, very sick patients with SM-AHN or MCL are easily recognized by hem-oncs.

“But if you see a patient in an ambulatory setting, in your clinic or whatever, and you’re suspicious, then you need to decide [how] you’re going to investigate that patient further,” he said, Dr. Orazi noted the next step is not always obvious, especially for primary-practice or internal medicine physicians likely to be unfamiliar with such a rare disease.

A practice survey published in 2022 by other researchers backed up Dr. Orazi’s remarks. The study found that community/solo-practice physicians were less likely to have tested systemic mastocytosis patients for KIT816V mutation than academic/specialty physicians (58% vs. 80%; P = .004; n = 111). Clinicians treating these patients estimated that it took an average of 8.5 months for a “typical” patient to receive the diagnosis from the time of symptom onset.

The research was headed by Ruben Mesa, MD, director of University of Texas Health, San Antonio, and funded by Blueprint Medicines, the manufacturer of avapritinib (Ayvakit), a new drug for the disease.

Dr. Orazi urged clinicians to have a high degree of suspicion for mastocytosis in a patient who walks into the clinic with any combination of the following: urticarial-type skin manifestations, especially if persistent into adulthood; history of undue reaction to an insect sting; a big spleen in a patient with a history of cutaneous flushing or rash; chronic diarrhea, especially if a biopsy has shown “too many mast cells” in the lamina propria of the small bowel; and positivity for KIT816V mutation.

Dr. Orazi stressed that the majority of patients will have indolent disease, but for the few patients for whom immediate treatment is essential, “the distinction between indolent and aggressive [disease] is really very, very important.”

Patients with advanced systemic mastocytosis can now be effectively treated, following the arrival of midostaurin (Rydapt, Tauritmo) and avapritinib.

Midostaurin, a multikinase/KIT inhibitor, was approved by the Food and Drug Administration in 2017 for the treatment of advanced systemic mastocytosis (ASM, SM-AHN, and MCL). Avapritinib, a selective kinase inhibitor of KIT816V and platelet-derived growth factor receptor alpha as well as multiple KIT exon 11, 11/17 and 17 mutants, gained the same indication in June 2021.

As with all rare diseases, it is challenging to obtain accurate numbers on how many patients are affected by systemic mastocytosis. The first population-based study of the disorder, presented at the 2018 annual meeting of the American Society of Hematology, used the Surveillance, Epidemiology, and End Results database from 2000 to 2014 to estimate incidence at 0.046 per 10,000, which translates to 1,050 new adult cases per year. The study data have never been published in full.

How many of these cases are advanced disease? There are no U.S. data but extrapolating from a Danish registry study that found 82% of systemic mastocytosis cases to be indolent disease, the incidence of advanced systemic mastocytosis in the United States could be as low as 200 adults a year.

This information, in turn, suggests that identifying more patients with advanced disease would not only benefit those patients but would also benefit clinical trial investigators who are seeking the proverbial needle in the haystack.

Nationwide, five clinical trials are recruiting individuals with advanced systemic mastocytosis, collectively looking for 352 patients in the United States. Two of the studies focus on mast-cell activation (NCT0544944) and cutaneous mastocytoses (NCT04846348). Two trials in a range of hematological malignancies are testing bispecific antibodies flotetuzumab and MGD024 (both from Macrogenics; NCT04681105, NCT05362773).

Apex, a phase 2 study of tyrosine-kinase inhibitor bezuclastinib (a Cogent hopeful), is specifically focusing on advanced disease. Dr. Gotlib and coinvestigators are aiming for 140 participants.

As a pathologist, Dr. Orazi said he find mastocytosis fascinating because he believes he has “a truly useful role,” contrasting with some other hematological diseases in which the molecular profile rules.

“Pathology plays a major role here,” he explained, “because you have to correlate what you see at the microscope with the full clinical picture, selected laboratory tests such as CBC and serum tryptase, and molecular results. You often need integration through a pathologist to put all the pieces together.

“It’s easier to treat once you know exactly what disease you’re dealing with and whether it is an aggressive or indolent subtype,” Dr. Orazi concluded.

Dr. Orazi disclosed no conflicts of interest. Dr. Gotlib has disclosed ties with Blueprint Medicines, Deciphera, Incyte, and Kartos Therapeutics, and has led committees for Blueprint Medicine’s EXPLORER and PATHFINDER studies, Deciphera’s Study Steering Committee for ripretinib in AdvSM, and the Central Response Review Committee for the phase 2 study of bezuclastinib in AdvSM.

Systemic mastocytosis is widely underdiagnosed, and many more hematologic oncologists should be looking for it. This call to action was issued late in 2022 by Stanford (Calif.) Cancer Institute’s Jason Gotlib, MD, speaking at the Lymphoma, Leukemia & Myeloma Congress in New York.

Nationwide, approximately 1,000 adults are diagnosed with systemic mastocytosis annually. This rare disease is a myeloid neoplasm with a highly variable phenotypic expression, in which abnormal mast cells proliferate and infiltrate organs and tissues. It swings widely from a nonadvanced form, composed of indolent or smoldering disease, to advanced disease that progresses to leukemia in 6% of cases.

More than 80% of systemic mastocytosis is driven by the KIT D816V mutation. Along with a host of other rare KIT mutations, KIT D816V activates KIT-receptor tyrosine kinase to trigger mast cell proliferation.

Dr. Gotlib could not be contacted for an interview. However, there are many good reasons to identify patients with systemic mastocytosis, according to Attilio Orazi, MD, professor and chair of the department of pathology at Texas Tech University, El Paso. The chief reason is that the patient may be in grave peril.

“The degree of heterogeneity is amazing. ... There’s very indolent [disease], which is really not a big deal. And then you have a disease in which you’re dead in 3 months,” Dr. Orazi said. “So you run the gamut between an indolent, no-problem cutaneous disease to a very nasty systemic, aggressive leukemia-like neoplasm.”

Since 2001, the diagnosis of mastocytosis has been guided by the World Health Organization Classification of Tumours, or “Blue Book.” In 2022, Dr. Orazi along with 137 other senior experts, most of whom were involved in past editions of the Blue Book, published their own version: The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (the ICC 2022).

In September 2021, this group of specialists held a virtual/in-person advisory committee meeting at the University of Chicago to create the document. One factor in their decision to go it alone, Dr. Orazi said, was that WHO decided to proceed with the fifth edition of the Blue Book using its own internal editorial group without convening an advisory committee, despite repeated requests to do so.

ICC 2022 divides advanced systemic mastocytosis into three subtypes: aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL). Median survival is 3.5 years for patients with ASM, 2 years for those with SM-AHN and as low as 2 months for MCL.

The second key reason to increase awareness of mastocytosis among physicians, said Dr. Orazi, is that patients falling through the net are likely to be ambulatory, and their presentation can be “a little confusing.”

Patients with indolent disease are relatively straightforward to recognize, explained Dr. Orazi. Similarly, very sick patients with SM-AHN or MCL are easily recognized by hem-oncs.

“But if you see a patient in an ambulatory setting, in your clinic or whatever, and you’re suspicious, then you need to decide [how] you’re going to investigate that patient further,” he said, Dr. Orazi noted the next step is not always obvious, especially for primary-practice or internal medicine physicians likely to be unfamiliar with such a rare disease.

A practice survey published in 2022 by other researchers backed up Dr. Orazi’s remarks. The study found that community/solo-practice physicians were less likely to have tested systemic mastocytosis patients for KIT816V mutation than academic/specialty physicians (58% vs. 80%; P = .004; n = 111). Clinicians treating these patients estimated that it took an average of 8.5 months for a “typical” patient to receive the diagnosis from the time of symptom onset.

The research was headed by Ruben Mesa, MD, director of University of Texas Health, San Antonio, and funded by Blueprint Medicines, the manufacturer of avapritinib (Ayvakit), a new drug for the disease.

Dr. Orazi urged clinicians to have a high degree of suspicion for mastocytosis in a patient who walks into the clinic with any combination of the following: urticarial-type skin manifestations, especially if persistent into adulthood; history of undue reaction to an insect sting; a big spleen in a patient with a history of cutaneous flushing or rash; chronic diarrhea, especially if a biopsy has shown “too many mast cells” in the lamina propria of the small bowel; and positivity for KIT816V mutation.

Dr. Orazi stressed that the majority of patients will have indolent disease, but for the few patients for whom immediate treatment is essential, “the distinction between indolent and aggressive [disease] is really very, very important.”

Patients with advanced systemic mastocytosis can now be effectively treated, following the arrival of midostaurin (Rydapt, Tauritmo) and avapritinib.

Midostaurin, a multikinase/KIT inhibitor, was approved by the Food and Drug Administration in 2017 for the treatment of advanced systemic mastocytosis (ASM, SM-AHN, and MCL). Avapritinib, a selective kinase inhibitor of KIT816V and platelet-derived growth factor receptor alpha as well as multiple KIT exon 11, 11/17 and 17 mutants, gained the same indication in June 2021.

As with all rare diseases, it is challenging to obtain accurate numbers on how many patients are affected by systemic mastocytosis. The first population-based study of the disorder, presented at the 2018 annual meeting of the American Society of Hematology, used the Surveillance, Epidemiology, and End Results database from 2000 to 2014 to estimate incidence at 0.046 per 10,000, which translates to 1,050 new adult cases per year. The study data have never been published in full.

How many of these cases are advanced disease? There are no U.S. data but extrapolating from a Danish registry study that found 82% of systemic mastocytosis cases to be indolent disease, the incidence of advanced systemic mastocytosis in the United States could be as low as 200 adults a year.

This information, in turn, suggests that identifying more patients with advanced disease would not only benefit those patients but would also benefit clinical trial investigators who are seeking the proverbial needle in the haystack.

Nationwide, five clinical trials are recruiting individuals with advanced systemic mastocytosis, collectively looking for 352 patients in the United States. Two of the studies focus on mast-cell activation (NCT0544944) and cutaneous mastocytoses (NCT04846348). Two trials in a range of hematological malignancies are testing bispecific antibodies flotetuzumab and MGD024 (both from Macrogenics; NCT04681105, NCT05362773).

Apex, a phase 2 study of tyrosine-kinase inhibitor bezuclastinib (a Cogent hopeful), is specifically focusing on advanced disease. Dr. Gotlib and coinvestigators are aiming for 140 participants.

As a pathologist, Dr. Orazi said he find mastocytosis fascinating because he believes he has “a truly useful role,” contrasting with some other hematological diseases in which the molecular profile rules.

“Pathology plays a major role here,” he explained, “because you have to correlate what you see at the microscope with the full clinical picture, selected laboratory tests such as CBC and serum tryptase, and molecular results. You often need integration through a pathologist to put all the pieces together.

“It’s easier to treat once you know exactly what disease you’re dealing with and whether it is an aggressive or indolent subtype,” Dr. Orazi concluded.

Dr. Orazi disclosed no conflicts of interest. Dr. Gotlib has disclosed ties with Blueprint Medicines, Deciphera, Incyte, and Kartos Therapeutics, and has led committees for Blueprint Medicine’s EXPLORER and PATHFINDER studies, Deciphera’s Study Steering Committee for ripretinib in AdvSM, and the Central Response Review Committee for the phase 2 study of bezuclastinib in AdvSM.

Systemic mastocytosis is widely underdiagnosed, and many more hematologic oncologists should be looking for it. This call to action was issued late in 2022 by Stanford (Calif.) Cancer Institute’s Jason Gotlib, MD, speaking at the Lymphoma, Leukemia & Myeloma Congress in New York.

Nationwide, approximately 1,000 adults are diagnosed with systemic mastocytosis annually. This rare disease is a myeloid neoplasm with a highly variable phenotypic expression, in which abnormal mast cells proliferate and infiltrate organs and tissues. It swings widely from a nonadvanced form, composed of indolent or smoldering disease, to advanced disease that progresses to leukemia in 6% of cases.

More than 80% of systemic mastocytosis is driven by the KIT D816V mutation. Along with a host of other rare KIT mutations, KIT D816V activates KIT-receptor tyrosine kinase to trigger mast cell proliferation.

Dr. Gotlib could not be contacted for an interview. However, there are many good reasons to identify patients with systemic mastocytosis, according to Attilio Orazi, MD, professor and chair of the department of pathology at Texas Tech University, El Paso. The chief reason is that the patient may be in grave peril.

“The degree of heterogeneity is amazing. ... There’s very indolent [disease], which is really not a big deal. And then you have a disease in which you’re dead in 3 months,” Dr. Orazi said. “So you run the gamut between an indolent, no-problem cutaneous disease to a very nasty systemic, aggressive leukemia-like neoplasm.”

Since 2001, the diagnosis of mastocytosis has been guided by the World Health Organization Classification of Tumours, or “Blue Book.” In 2022, Dr. Orazi along with 137 other senior experts, most of whom were involved in past editions of the Blue Book, published their own version: The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (the ICC 2022).

In September 2021, this group of specialists held a virtual/in-person advisory committee meeting at the University of Chicago to create the document. One factor in their decision to go it alone, Dr. Orazi said, was that WHO decided to proceed with the fifth edition of the Blue Book using its own internal editorial group without convening an advisory committee, despite repeated requests to do so.

ICC 2022 divides advanced systemic mastocytosis into three subtypes: aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL). Median survival is 3.5 years for patients with ASM, 2 years for those with SM-AHN and as low as 2 months for MCL.

The second key reason to increase awareness of mastocytosis among physicians, said Dr. Orazi, is that patients falling through the net are likely to be ambulatory, and their presentation can be “a little confusing.”

Patients with indolent disease are relatively straightforward to recognize, explained Dr. Orazi. Similarly, very sick patients with SM-AHN or MCL are easily recognized by hem-oncs.

“But if you see a patient in an ambulatory setting, in your clinic or whatever, and you’re suspicious, then you need to decide [how] you’re going to investigate that patient further,” he said, Dr. Orazi noted the next step is not always obvious, especially for primary-practice or internal medicine physicians likely to be unfamiliar with such a rare disease.

A practice survey published in 2022 by other researchers backed up Dr. Orazi’s remarks. The study found that community/solo-practice physicians were less likely to have tested systemic mastocytosis patients for KIT816V mutation than academic/specialty physicians (58% vs. 80%; P = .004; n = 111). Clinicians treating these patients estimated that it took an average of 8.5 months for a “typical” patient to receive the diagnosis from the time of symptom onset.

The research was headed by Ruben Mesa, MD, director of University of Texas Health, San Antonio, and funded by Blueprint Medicines, the manufacturer of avapritinib (Ayvakit), a new drug for the disease.

Dr. Orazi urged clinicians to have a high degree of suspicion for mastocytosis in a patient who walks into the clinic with any combination of the following: urticarial-type skin manifestations, especially if persistent into adulthood; history of undue reaction to an insect sting; a big spleen in a patient with a history of cutaneous flushing or rash; chronic diarrhea, especially if a biopsy has shown “too many mast cells” in the lamina propria of the small bowel; and positivity for KIT816V mutation.

Dr. Orazi stressed that the majority of patients will have indolent disease, but for the few patients for whom immediate treatment is essential, “the distinction between indolent and aggressive [disease] is really very, very important.”

Patients with advanced systemic mastocytosis can now be effectively treated, following the arrival of midostaurin (Rydapt, Tauritmo) and avapritinib.

Midostaurin, a multikinase/KIT inhibitor, was approved by the Food and Drug Administration in 2017 for the treatment of advanced systemic mastocytosis (ASM, SM-AHN, and MCL). Avapritinib, a selective kinase inhibitor of KIT816V and platelet-derived growth factor receptor alpha as well as multiple KIT exon 11, 11/17 and 17 mutants, gained the same indication in June 2021.

As with all rare diseases, it is challenging to obtain accurate numbers on how many patients are affected by systemic mastocytosis. The first population-based study of the disorder, presented at the 2018 annual meeting of the American Society of Hematology, used the Surveillance, Epidemiology, and End Results database from 2000 to 2014 to estimate incidence at 0.046 per 10,000, which translates to 1,050 new adult cases per year. The study data have never been published in full.

How many of these cases are advanced disease? There are no U.S. data but extrapolating from a Danish registry study that found 82% of systemic mastocytosis cases to be indolent disease, the incidence of advanced systemic mastocytosis in the United States could be as low as 200 adults a year.

This information, in turn, suggests that identifying more patients with advanced disease would not only benefit those patients but would also benefit clinical trial investigators who are seeking the proverbial needle in the haystack.

Nationwide, five clinical trials are recruiting individuals with advanced systemic mastocytosis, collectively looking for 352 patients in the United States. Two of the studies focus on mast-cell activation (NCT0544944) and cutaneous mastocytoses (NCT04846348). Two trials in a range of hematological malignancies are testing bispecific antibodies flotetuzumab and MGD024 (both from Macrogenics; NCT04681105, NCT05362773).

Apex, a phase 2 study of tyrosine-kinase inhibitor bezuclastinib (a Cogent hopeful), is specifically focusing on advanced disease. Dr. Gotlib and coinvestigators are aiming for 140 participants.

As a pathologist, Dr. Orazi said he find mastocytosis fascinating because he believes he has “a truly useful role,” contrasting with some other hematological diseases in which the molecular profile rules.

“Pathology plays a major role here,” he explained, “because you have to correlate what you see at the microscope with the full clinical picture, selected laboratory tests such as CBC and serum tryptase, and molecular results. You often need integration through a pathologist to put all the pieces together.

“It’s easier to treat once you know exactly what disease you’re dealing with and whether it is an aggressive or indolent subtype,” Dr. Orazi concluded.

Dr. Orazi disclosed no conflicts of interest. Dr. Gotlib has disclosed ties with Blueprint Medicines, Deciphera, Incyte, and Kartos Therapeutics, and has led committees for Blueprint Medicine’s EXPLORER and PATHFINDER studies, Deciphera’s Study Steering Committee for ripretinib in AdvSM, and the Central Response Review Committee for the phase 2 study of bezuclastinib in AdvSM.

Adding venetoclax to ibrutinib for chronic lymphocytic leukemia (CLL) improved rates of durable, treatment-free remission among 45 patients at the University of Texas MD Anderson Cancer Center, Houston.

Investigators led by Philip Thompson, MD, a hematologist/oncologist at the center, explained that CLL patients receiving ibrutinib, a Bruton’s kinase inhibitor, “rarely achieve complete remission with undetectable measurable residual disease,” so they stay on the costly treatment indefinitely or until disease progression or accumulating adverse events force a switch to venetoclax.

Using the two agents together, instead of consecutively, may allow strong responders to stop treatment altogether and suboptimal responders to have longer remissions, they said.

“We would not advocate prolonged Bruton’s kinase inhibitor use prior to starting venetoclax in treatment-naive patients, as the safety and efficacy of commencing venetoclax after a 3-month ibrutinib monotherapy phase has been repeatedly demonstrated,” the team said.

However, the investigators noted that their “study was not intended to directly answer the question of whether combination therapy is superior to the current paradigm of sequential monotherapy.” Randomized trials are looking into the matter. The study was published recently as a preprint on ResearchSquare.com and has not been peer reviewed.
 

Complete remission in over half

The 45 adult subjects had one or more high-risk features for CLL progression and had received at least 1 year of ibrutinib at 140-420 mg once daily, depending on tolerance. They had bone marrow detectable disease at study entry but did not meet criteria for progression. Median duration of ibrutinib at baseline was 32 months, and about half the subjects were on it as their initial therapy.

Venetoclax, a BCL2 inhibitor with a completely different mechanisms of action, was added to ibrutinib for up to 2 years, escalated up to a target dose of 400 mg once daily.

On intention-to-treat analysis, venetoclax add-on improved ibrutinib response to complete remission in 55% of patients; complete remission was defined as less than 1 CLL cell per 10,000 leukocytes in bone marrow on two consecutive occasions 6 months apart.

The rate of undetectable bone marrow disease was 57% after 1 year of combined treatment and 71% after venetoclax completion, at which point 23 patients with undetectable disease stopped ibrutinib along with venetoclax.

Five patients had disease progression at a median of 41 months after venetoclax initiation, one during combined therapy, three during ibrutinib maintenance afterward, and one with Richter transformation after complete remission and discontinuation of all treatment. No patient had died from CLL.

“There has so far been no significant difference noted in” time to residual disease re-emergence, the team said, based on whether or not patients continued ibrutinib after venetoclax add-on.

There was no significant difference in the rate of bone marrow clearance according to the presence or absence of TP53 abnormalities, complex karyotypes, or prior treatment status.

The most common grade 3/4 adverse event was neutropenia in 20% of patients. Nine patients developed nonmelanoma skin cancer during the trial; six were diagnosed with other solid tumors; three came down with grade 3 infections, and two developed myelodysplastic syndrome, both with a prior history of chemotherapy.

No one stopped venetoclax because of toxicity, but about a third of subjects required dose reductions, most often because of neutropenia.

The study was funded by AbbVie, which is commercializing venetoclax along with Genentech. Investigators disclosed ties to both companies and many others. Dr. Thompson disclosed ties to AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, Beigene, and Genentech.

Adding venetoclax to ibrutinib for chronic lymphocytic leukemia (CLL) improved rates of durable, treatment-free remission among 45 patients at the University of Texas MD Anderson Cancer Center, Houston.

Investigators led by Philip Thompson, MD, a hematologist/oncologist at the center, explained that CLL patients receiving ibrutinib, a Bruton’s kinase inhibitor, “rarely achieve complete remission with undetectable measurable residual disease,” so they stay on the costly treatment indefinitely or until disease progression or accumulating adverse events force a switch to venetoclax.

Using the two agents together, instead of consecutively, may allow strong responders to stop treatment altogether and suboptimal responders to have longer remissions, they said.

“We would not advocate prolonged Bruton’s kinase inhibitor use prior to starting venetoclax in treatment-naive patients, as the safety and efficacy of commencing venetoclax after a 3-month ibrutinib monotherapy phase has been repeatedly demonstrated,” the team said.

However, the investigators noted that their “study was not intended to directly answer the question of whether combination therapy is superior to the current paradigm of sequential monotherapy.” Randomized trials are looking into the matter. The study was published recently as a preprint on ResearchSquare.com and has not been peer reviewed.
 

Complete remission in over half

The 45 adult subjects had one or more high-risk features for CLL progression and had received at least 1 year of ibrutinib at 140-420 mg once daily, depending on tolerance. They had bone marrow detectable disease at study entry but did not meet criteria for progression. Median duration of ibrutinib at baseline was 32 months, and about half the subjects were on it as their initial therapy.

Venetoclax, a BCL2 inhibitor with a completely different mechanisms of action, was added to ibrutinib for up to 2 years, escalated up to a target dose of 400 mg once daily.

On intention-to-treat analysis, venetoclax add-on improved ibrutinib response to complete remission in 55% of patients; complete remission was defined as less than 1 CLL cell per 10,000 leukocytes in bone marrow on two consecutive occasions 6 months apart.

The rate of undetectable bone marrow disease was 57% after 1 year of combined treatment and 71% after venetoclax completion, at which point 23 patients with undetectable disease stopped ibrutinib along with venetoclax.

Five patients had disease progression at a median of 41 months after venetoclax initiation, one during combined therapy, three during ibrutinib maintenance afterward, and one with Richter transformation after complete remission and discontinuation of all treatment. No patient had died from CLL.

“There has so far been no significant difference noted in” time to residual disease re-emergence, the team said, based on whether or not patients continued ibrutinib after venetoclax add-on.

There was no significant difference in the rate of bone marrow clearance according to the presence or absence of TP53 abnormalities, complex karyotypes, or prior treatment status.

The most common grade 3/4 adverse event was neutropenia in 20% of patients. Nine patients developed nonmelanoma skin cancer during the trial; six were diagnosed with other solid tumors; three came down with grade 3 infections, and two developed myelodysplastic syndrome, both with a prior history of chemotherapy.

No one stopped venetoclax because of toxicity, but about a third of subjects required dose reductions, most often because of neutropenia.

The study was funded by AbbVie, which is commercializing venetoclax along with Genentech. Investigators disclosed ties to both companies and many others. Dr. Thompson disclosed ties to AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, Beigene, and Genentech.

Adding venetoclax to ibrutinib for chronic lymphocytic leukemia (CLL) improved rates of durable, treatment-free remission among 45 patients at the University of Texas MD Anderson Cancer Center, Houston.

Investigators led by Philip Thompson, MD, a hematologist/oncologist at the center, explained that CLL patients receiving ibrutinib, a Bruton’s kinase inhibitor, “rarely achieve complete remission with undetectable measurable residual disease,” so they stay on the costly treatment indefinitely or until disease progression or accumulating adverse events force a switch to venetoclax.

Using the two agents together, instead of consecutively, may allow strong responders to stop treatment altogether and suboptimal responders to have longer remissions, they said.

“We would not advocate prolonged Bruton’s kinase inhibitor use prior to starting venetoclax in treatment-naive patients, as the safety and efficacy of commencing venetoclax after a 3-month ibrutinib monotherapy phase has been repeatedly demonstrated,” the team said.

However, the investigators noted that their “study was not intended to directly answer the question of whether combination therapy is superior to the current paradigm of sequential monotherapy.” Randomized trials are looking into the matter. The study was published recently as a preprint on ResearchSquare.com and has not been peer reviewed.
 

Complete remission in over half

The 45 adult subjects had one or more high-risk features for CLL progression and had received at least 1 year of ibrutinib at 140-420 mg once daily, depending on tolerance. They had bone marrow detectable disease at study entry but did not meet criteria for progression. Median duration of ibrutinib at baseline was 32 months, and about half the subjects were on it as their initial therapy.

Venetoclax, a BCL2 inhibitor with a completely different mechanisms of action, was added to ibrutinib for up to 2 years, escalated up to a target dose of 400 mg once daily.

On intention-to-treat analysis, venetoclax add-on improved ibrutinib response to complete remission in 55% of patients; complete remission was defined as less than 1 CLL cell per 10,000 leukocytes in bone marrow on two consecutive occasions 6 months apart.

The rate of undetectable bone marrow disease was 57% after 1 year of combined treatment and 71% after venetoclax completion, at which point 23 patients with undetectable disease stopped ibrutinib along with venetoclax.

Five patients had disease progression at a median of 41 months after venetoclax initiation, one during combined therapy, three during ibrutinib maintenance afterward, and one with Richter transformation after complete remission and discontinuation of all treatment. No patient had died from CLL.

“There has so far been no significant difference noted in” time to residual disease re-emergence, the team said, based on whether or not patients continued ibrutinib after venetoclax add-on.

There was no significant difference in the rate of bone marrow clearance according to the presence or absence of TP53 abnormalities, complex karyotypes, or prior treatment status.

The most common grade 3/4 adverse event was neutropenia in 20% of patients. Nine patients developed nonmelanoma skin cancer during the trial; six were diagnosed with other solid tumors; three came down with grade 3 infections, and two developed myelodysplastic syndrome, both with a prior history of chemotherapy.

No one stopped venetoclax because of toxicity, but about a third of subjects required dose reductions, most often because of neutropenia.

The study was funded by AbbVie, which is commercializing venetoclax along with Genentech. Investigators disclosed ties to both companies and many others. Dr. Thompson disclosed ties to AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, Beigene, and Genentech.