Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail. 

When I met him in December 2023, he had hit rock bottom and was willing to try anything.

At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone. 

Richard shared some feedback after his first 2 weeks:

The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.

And after 6 weeks:

Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.

And finally, after 8 weeks:

Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you. 

Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine. 

Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors. 

Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone. 

At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity. 

*Patient’s name has been changed.
 

Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail. 

When I met him in December 2023, he had hit rock bottom and was willing to try anything.

At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone. 

Richard shared some feedback after his first 2 weeks:

The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.

And after 6 weeks:

Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.

And finally, after 8 weeks:

Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you. 

Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine. 

Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors. 

Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone. 

At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity. 

*Patient’s name has been changed.
 

Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail. 

When I met him in December 2023, he had hit rock bottom and was willing to try anything.

At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone. 

Richard shared some feedback after his first 2 weeks:

The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.

And after 6 weeks:

Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.

And finally, after 8 weeks:

Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you. 

Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine. 

Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors. 

Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone. 

At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity. 

*Patient’s name has been changed.
 

Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Three different definitions of nonanemic iron deficiency (ID), a common disorder causing substantial morbidity in women, were significantly associated with different population prevalence estimates, a data analysis of the cross-sectional Hemochromatosis and Iron Overload Screening Study (HEIRS) study found.

These differences held, regardless of self-reported age, pregnancy, or race and ethnicity, according to HEIRS researchers led by James C. Barton, MD, professor of hematology at the University of Alabama at Birmingham.

“Using higher serum ferritin thresholds to define ID could lead to diagnosis and treatment of more women with ID and greater reduction of related morbidity,” the investigators wrote. The study was published in JAMA Network Open.

The authors noted that ID affects about 2 billion people worldwide, mainly women and children, increasing risks of fatigue, impaired muscular performance, cold intolerance, mucosal and epithelial abnormalities, pica, disturbances of menstruation, and adverse pregnancy outcomes.

Manifestations of ID, including anemia, are less prevalent or less severe in adults with higher serum ferritin (SF), and the three definitions correspond, in sequence, to ID of increasing prevalence and decreasing severity, they explained.
 

The Study

HEIRS conducted multiethnic, primary care–based screening for iron disorders during 2001-2003 at four field centers in the United States and one in Canada at primary care venues.

In data for the current study analyzed from June to December, 2023, the three ID definitions were: combined transferrin saturation less than 10% and SF less than 15 ng/mL (HEIRS); SF less than 15 ng/mL (World Health Organization [WHO]); and SF less than 25 ng/mL, the threshold for ID-deficient erythropoiesis [IDE).

Among the cohort’s 62,685 women (mean age, 49.58 years, 27,072 White, 17,272 Black), the estimated prevalence of ID emerged as follows across the different definitions:

• 1957 (3.12%) according to HEIRS
• 4659 (7.43%) according to WHO
• 9611 (15.33%) according to IDE

Those figures translated to an increased relative ID prevalence of 2.4-fold (95% CI, 2.3-2.5; P < .001) according to the WHO standard and 4.9-fold (95% CI, 4.7-5.2; P < .001) according IDEs.

In addition, prevalence was higher in younger women, and within each racial and ethnic subgroup of participants aged 25-54 years, prevalence rose significantly from the HEIRS definition to the WHO and IDE definitions.

Notably, ID was significantly higher among Black and Hispanic participants than Asian and White participants.

An accompanying editorial pointed to gender-based health equity issues raised by the HEIRS analysis and argued that a similar passive acceptance of laboratory definitions of a debilitating but correctable condition in White males would be “frankly unimaginable.”

“Iron deficiency is the leading cause of years lived with disability among women of reproductive age,” wrote hematologist Michelle Sholzberg, MDCM, MSc, and Grace H. Tang, MSc, of St. Michael’s Hospital in Toronto, Canada. “It is a factor clearly associated with maternal death and morbidity (including diminished IQ), and it is correctable, and, thus, unnecessary, in high-income, middle-income, and low-income geographic settings.”

The authors listed no specific funding for this analysis of HEIRS data. Dr. Barton reported contracts from the National Institutes of Health, National Human Genome Research Institute, outside of the submitted work. A coauthor reported grants from the National Heart, Lung, and Blood Institute and the National Human Genome Research Institute outside of the submitted work. Dr. Sholzberg reported unrestricted research funding to her institution from Octapharma and Pfizer and speakers’ honoraria from Takeda, Sobi, and Medison outside of the submitted work.

Three different definitions of nonanemic iron deficiency (ID), a common disorder causing substantial morbidity in women, were significantly associated with different population prevalence estimates, a data analysis of the cross-sectional Hemochromatosis and Iron Overload Screening Study (HEIRS) study found.

These differences held, regardless of self-reported age, pregnancy, or race and ethnicity, according to HEIRS researchers led by James C. Barton, MD, professor of hematology at the University of Alabama at Birmingham.

“Using higher serum ferritin thresholds to define ID could lead to diagnosis and treatment of more women with ID and greater reduction of related morbidity,” the investigators wrote. The study was published in JAMA Network Open.

The authors noted that ID affects about 2 billion people worldwide, mainly women and children, increasing risks of fatigue, impaired muscular performance, cold intolerance, mucosal and epithelial abnormalities, pica, disturbances of menstruation, and adverse pregnancy outcomes.

Manifestations of ID, including anemia, are less prevalent or less severe in adults with higher serum ferritin (SF), and the three definitions correspond, in sequence, to ID of increasing prevalence and decreasing severity, they explained.
 

The Study

HEIRS conducted multiethnic, primary care–based screening for iron disorders during 2001-2003 at four field centers in the United States and one in Canada at primary care venues.

In data for the current study analyzed from June to December, 2023, the three ID definitions were: combined transferrin saturation less than 10% and SF less than 15 ng/mL (HEIRS); SF less than 15 ng/mL (World Health Organization [WHO]); and SF less than 25 ng/mL, the threshold for ID-deficient erythropoiesis [IDE).

Among the cohort’s 62,685 women (mean age, 49.58 years, 27,072 White, 17,272 Black), the estimated prevalence of ID emerged as follows across the different definitions:

• 1957 (3.12%) according to HEIRS
• 4659 (7.43%) according to WHO
• 9611 (15.33%) according to IDE

Those figures translated to an increased relative ID prevalence of 2.4-fold (95% CI, 2.3-2.5; P < .001) according to the WHO standard and 4.9-fold (95% CI, 4.7-5.2; P < .001) according IDEs.

In addition, prevalence was higher in younger women, and within each racial and ethnic subgroup of participants aged 25-54 years, prevalence rose significantly from the HEIRS definition to the WHO and IDE definitions.

Notably, ID was significantly higher among Black and Hispanic participants than Asian and White participants.

An accompanying editorial pointed to gender-based health equity issues raised by the HEIRS analysis and argued that a similar passive acceptance of laboratory definitions of a debilitating but correctable condition in White males would be “frankly unimaginable.”

“Iron deficiency is the leading cause of years lived with disability among women of reproductive age,” wrote hematologist Michelle Sholzberg, MDCM, MSc, and Grace H. Tang, MSc, of St. Michael’s Hospital in Toronto, Canada. “It is a factor clearly associated with maternal death and morbidity (including diminished IQ), and it is correctable, and, thus, unnecessary, in high-income, middle-income, and low-income geographic settings.”

The authors listed no specific funding for this analysis of HEIRS data. Dr. Barton reported contracts from the National Institutes of Health, National Human Genome Research Institute, outside of the submitted work. A coauthor reported grants from the National Heart, Lung, and Blood Institute and the National Human Genome Research Institute outside of the submitted work. Dr. Sholzberg reported unrestricted research funding to her institution from Octapharma and Pfizer and speakers’ honoraria from Takeda, Sobi, and Medison outside of the submitted work.

Three different definitions of nonanemic iron deficiency (ID), a common disorder causing substantial morbidity in women, were significantly associated with different population prevalence estimates, a data analysis of the cross-sectional Hemochromatosis and Iron Overload Screening Study (HEIRS) study found.

These differences held, regardless of self-reported age, pregnancy, or race and ethnicity, according to HEIRS researchers led by James C. Barton, MD, professor of hematology at the University of Alabama at Birmingham.

“Using higher serum ferritin thresholds to define ID could lead to diagnosis and treatment of more women with ID and greater reduction of related morbidity,” the investigators wrote. The study was published in JAMA Network Open.

The authors noted that ID affects about 2 billion people worldwide, mainly women and children, increasing risks of fatigue, impaired muscular performance, cold intolerance, mucosal and epithelial abnormalities, pica, disturbances of menstruation, and adverse pregnancy outcomes.

Manifestations of ID, including anemia, are less prevalent or less severe in adults with higher serum ferritin (SF), and the three definitions correspond, in sequence, to ID of increasing prevalence and decreasing severity, they explained.
 

The Study

HEIRS conducted multiethnic, primary care–based screening for iron disorders during 2001-2003 at four field centers in the United States and one in Canada at primary care venues.

In data for the current study analyzed from June to December, 2023, the three ID definitions were: combined transferrin saturation less than 10% and SF less than 15 ng/mL (HEIRS); SF less than 15 ng/mL (World Health Organization [WHO]); and SF less than 25 ng/mL, the threshold for ID-deficient erythropoiesis [IDE).

Among the cohort’s 62,685 women (mean age, 49.58 years, 27,072 White, 17,272 Black), the estimated prevalence of ID emerged as follows across the different definitions:

• 1957 (3.12%) according to HEIRS
• 4659 (7.43%) according to WHO
• 9611 (15.33%) according to IDE

Those figures translated to an increased relative ID prevalence of 2.4-fold (95% CI, 2.3-2.5; P < .001) according to the WHO standard and 4.9-fold (95% CI, 4.7-5.2; P < .001) according IDEs.

In addition, prevalence was higher in younger women, and within each racial and ethnic subgroup of participants aged 25-54 years, prevalence rose significantly from the HEIRS definition to the WHO and IDE definitions.

Notably, ID was significantly higher among Black and Hispanic participants than Asian and White participants.

An accompanying editorial pointed to gender-based health equity issues raised by the HEIRS analysis and argued that a similar passive acceptance of laboratory definitions of a debilitating but correctable condition in White males would be “frankly unimaginable.”

“Iron deficiency is the leading cause of years lived with disability among women of reproductive age,” wrote hematologist Michelle Sholzberg, MDCM, MSc, and Grace H. Tang, MSc, of St. Michael’s Hospital in Toronto, Canada. “It is a factor clearly associated with maternal death and morbidity (including diminished IQ), and it is correctable, and, thus, unnecessary, in high-income, middle-income, and low-income geographic settings.”

The authors listed no specific funding for this analysis of HEIRS data. Dr. Barton reported contracts from the National Institutes of Health, National Human Genome Research Institute, outside of the submitted work. A coauthor reported grants from the National Heart, Lung, and Blood Institute and the National Human Genome Research Institute outside of the submitted work. Dr. Sholzberg reported unrestricted research funding to her institution from Octapharma and Pfizer and speakers’ honoraria from Takeda, Sobi, and Medison outside of the submitted work.

Dual therapy of ibrutinib (Imbruvica) and venetoclax (Venclexta) produced “promising” and comparable efficacy across cohorts of patients with mantle cell lymphoma (MCL) and TP53 mutations, a new analysis of the randomized, double-blind, phase 3 Sympatico study finds.

In first-line patients (n = 29) and relapsed/refractory patients (n = 45) with TP53 mutations, complete response rates were 55% and 58%, respectively, reported hematologist-oncologist Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, and colleagues, at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

“These results are encouraging in light of the poor responses and shorter survival outcomes with standard chemotherapy,” Dr. Wang said in an ASCO presentation.

The current standard of care for relapsed/refractory MCL includes Bruton tyrosine kinase inhibitors for first relapse and CAR T-cell therapy (CAR-T) for second relapse in eligible patients or pirtobrutinib (Jaypirca) in patients ineligible for CAR T-cell therapy, Ohio State University Comprehensive Cancer Center hematology specialist Narendranath Epperla, MD, MS, said in an interview. Dr. Epperla is familiar with the new study findings but didn’t take part in the research.

Options for third relapse and beyond include clinical trial, rituximab [Rituxan] and lenalidomide [Revlimid], and bortezomib [Velcade],” Dr. Epperla said. “Venetoclax is not currently FDA-approved but can also be considered at third relapse.”

Better therapies are needed for a number of reasons, including poor outcomes in high-risk patients, such as those with TP53 mutations and those who progress following CAR T, Dr. Epperla said. Also, “as the novel agents are being moved into earlier lines of therapy, there remains an unmet need in those who progress on these agents with fewer options in the relapsed setting.”

At last December’s American Society of Hematology annual meeting, Dr. Wang and colleagues reported on the primary analysis results from the Sympatico study. Patients with relapsed/refractory MCL after 1-5 prior therapies were randomly assigned to receive 560 mg of ibrutinib once daily with either placebo (n = 133) or 400 mg daily of venetoclax after ramp-up (n = 134) for 2 years. Then subjects continued taking ibrutinib alone until their disease progressed or they reached unacceptable toxicity.

At a median follow-up of 51.2 months, median progression-free survival was longer in the ibrutinib-venetoclax group vs. ibrutinib alone (hazard ratio [HR] = 0.65, 95% CI, P = .0052).

The new analysis pools several cohorts of patients with TP53 mutations who all took the combination therapy: 5 from a safety run-in phase, 40 from the randomized phase, and 29 from a first-line cohort (median age at baseline = 67).

Median overall survival was not reached in the first-line group and 35.0 months in the relapsed/refractory group (total = 47.1 months). Median progress-free survival in the groups was 22.0 months and 20.9 months, respectively, and median duration of response was 20.5 months and 26.5 months, respectively.

With regard to the new findings, “it is good to see the responses with ibrutinib and venetoclax were deep and durable,” Dr. Epperla said. The combination treatment “provides a good alternative option for TP53-mutated MCL patients who are ineligible for CAR-T.”

Dr. Epperla added that the findings about the addition of ibrutinib could apply to newer-generation Bruton tyrosine kinase inhibitors that have relatively better safety profiles.

However, Dr. Epperla cautioned that the treatment needs to be weighed against the toxicity and cost of the regimen of ibrutinib and venetoclax for 2 years then single-agent ibrutinib until progression or unacceptable toxicity.

This news organization reported in 2023 that estimated net spending on ibrutinib per Medicare data increased by nearly half from 2014-2020, reaching $11,980 in 2020 vs. $7,787 for venetoclax.

Dr. Epperla also noted that “there are newer therapies that are emerging, such as T-cell-engaging bispecific antibodies, and they have shown promising results.”

In an interview, Brad S. Kahl, MD, a hematologist-oncologist at Washington University, St. Louis, said the improvement in outcomes are “modestly significant.”

Dr. Kahl, who is familiar with the study findings but didn’t take part in the research, said it is “worth adding the venetoclax, particularly in these biologically high risk patients with p53 mutations. Venetoclax is not FDA-approved, so insurance approval will need to be determined on a case-by-case basis. The combination is very expensive.”

Dr. Kahl agreed with Dr. Epperla that the findings could be extrapolated to other Bruton tyrosine kinase inhibitors.

The study was funded by Pharmacyclics, an AbbVie Company. Dr. Epperla disclosed relationships with BeiGene and Eli Lilly. Dr. Kahl reported ties with AstraZeneca, BeiGene, Abbvie, and Genentech.

Dual therapy of ibrutinib (Imbruvica) and venetoclax (Venclexta) produced “promising” and comparable efficacy across cohorts of patients with mantle cell lymphoma (MCL) and TP53 mutations, a new analysis of the randomized, double-blind, phase 3 Sympatico study finds.

In first-line patients (n = 29) and relapsed/refractory patients (n = 45) with TP53 mutations, complete response rates were 55% and 58%, respectively, reported hematologist-oncologist Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, and colleagues, at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

“These results are encouraging in light of the poor responses and shorter survival outcomes with standard chemotherapy,” Dr. Wang said in an ASCO presentation.

The current standard of care for relapsed/refractory MCL includes Bruton tyrosine kinase inhibitors for first relapse and CAR T-cell therapy (CAR-T) for second relapse in eligible patients or pirtobrutinib (Jaypirca) in patients ineligible for CAR T-cell therapy, Ohio State University Comprehensive Cancer Center hematology specialist Narendranath Epperla, MD, MS, said in an interview. Dr. Epperla is familiar with the new study findings but didn’t take part in the research.

Options for third relapse and beyond include clinical trial, rituximab [Rituxan] and lenalidomide [Revlimid], and bortezomib [Velcade],” Dr. Epperla said. “Venetoclax is not currently FDA-approved but can also be considered at third relapse.”

Better therapies are needed for a number of reasons, including poor outcomes in high-risk patients, such as those with TP53 mutations and those who progress following CAR T, Dr. Epperla said. Also, “as the novel agents are being moved into earlier lines of therapy, there remains an unmet need in those who progress on these agents with fewer options in the relapsed setting.”

At last December’s American Society of Hematology annual meeting, Dr. Wang and colleagues reported on the primary analysis results from the Sympatico study. Patients with relapsed/refractory MCL after 1-5 prior therapies were randomly assigned to receive 560 mg of ibrutinib once daily with either placebo (n = 133) or 400 mg daily of venetoclax after ramp-up (n = 134) for 2 years. Then subjects continued taking ibrutinib alone until their disease progressed or they reached unacceptable toxicity.

At a median follow-up of 51.2 months, median progression-free survival was longer in the ibrutinib-venetoclax group vs. ibrutinib alone (hazard ratio [HR] = 0.65, 95% CI, P = .0052).

The new analysis pools several cohorts of patients with TP53 mutations who all took the combination therapy: 5 from a safety run-in phase, 40 from the randomized phase, and 29 from a first-line cohort (median age at baseline = 67).

Median overall survival was not reached in the first-line group and 35.0 months in the relapsed/refractory group (total = 47.1 months). Median progress-free survival in the groups was 22.0 months and 20.9 months, respectively, and median duration of response was 20.5 months and 26.5 months, respectively.

With regard to the new findings, “it is good to see the responses with ibrutinib and venetoclax were deep and durable,” Dr. Epperla said. The combination treatment “provides a good alternative option for TP53-mutated MCL patients who are ineligible for CAR-T.”

Dr. Epperla added that the findings about the addition of ibrutinib could apply to newer-generation Bruton tyrosine kinase inhibitors that have relatively better safety profiles.

However, Dr. Epperla cautioned that the treatment needs to be weighed against the toxicity and cost of the regimen of ibrutinib and venetoclax for 2 years then single-agent ibrutinib until progression or unacceptable toxicity.

This news organization reported in 2023 that estimated net spending on ibrutinib per Medicare data increased by nearly half from 2014-2020, reaching $11,980 in 2020 vs. $7,787 for venetoclax.

Dr. Epperla also noted that “there are newer therapies that are emerging, such as T-cell-engaging bispecific antibodies, and they have shown promising results.”

In an interview, Brad S. Kahl, MD, a hematologist-oncologist at Washington University, St. Louis, said the improvement in outcomes are “modestly significant.”

Dr. Kahl, who is familiar with the study findings but didn’t take part in the research, said it is “worth adding the venetoclax, particularly in these biologically high risk patients with p53 mutations. Venetoclax is not FDA-approved, so insurance approval will need to be determined on a case-by-case basis. The combination is very expensive.”

Dr. Kahl agreed with Dr. Epperla that the findings could be extrapolated to other Bruton tyrosine kinase inhibitors.

The study was funded by Pharmacyclics, an AbbVie Company. Dr. Epperla disclosed relationships with BeiGene and Eli Lilly. Dr. Kahl reported ties with AstraZeneca, BeiGene, Abbvie, and Genentech.

Dual therapy of ibrutinib (Imbruvica) and venetoclax (Venclexta) produced “promising” and comparable efficacy across cohorts of patients with mantle cell lymphoma (MCL) and TP53 mutations, a new analysis of the randomized, double-blind, phase 3 Sympatico study finds.

In first-line patients (n = 29) and relapsed/refractory patients (n = 45) with TP53 mutations, complete response rates were 55% and 58%, respectively, reported hematologist-oncologist Michael Wang, MD, of the University of Texas MD Anderson Cancer Center, and colleagues, at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

“These results are encouraging in light of the poor responses and shorter survival outcomes with standard chemotherapy,” Dr. Wang said in an ASCO presentation.

The current standard of care for relapsed/refractory MCL includes Bruton tyrosine kinase inhibitors for first relapse and CAR T-cell therapy (CAR-T) for second relapse in eligible patients or pirtobrutinib (Jaypirca) in patients ineligible for CAR T-cell therapy, Ohio State University Comprehensive Cancer Center hematology specialist Narendranath Epperla, MD, MS, said in an interview. Dr. Epperla is familiar with the new study findings but didn’t take part in the research.

Options for third relapse and beyond include clinical trial, rituximab [Rituxan] and lenalidomide [Revlimid], and bortezomib [Velcade],” Dr. Epperla said. “Venetoclax is not currently FDA-approved but can also be considered at third relapse.”

Better therapies are needed for a number of reasons, including poor outcomes in high-risk patients, such as those with TP53 mutations and those who progress following CAR T, Dr. Epperla said. Also, “as the novel agents are being moved into earlier lines of therapy, there remains an unmet need in those who progress on these agents with fewer options in the relapsed setting.”

At last December’s American Society of Hematology annual meeting, Dr. Wang and colleagues reported on the primary analysis results from the Sympatico study. Patients with relapsed/refractory MCL after 1-5 prior therapies were randomly assigned to receive 560 mg of ibrutinib once daily with either placebo (n = 133) or 400 mg daily of venetoclax after ramp-up (n = 134) for 2 years. Then subjects continued taking ibrutinib alone until their disease progressed or they reached unacceptable toxicity.

At a median follow-up of 51.2 months, median progression-free survival was longer in the ibrutinib-venetoclax group vs. ibrutinib alone (hazard ratio [HR] = 0.65, 95% CI, P = .0052).

The new analysis pools several cohorts of patients with TP53 mutations who all took the combination therapy: 5 from a safety run-in phase, 40 from the randomized phase, and 29 from a first-line cohort (median age at baseline = 67).

Median overall survival was not reached in the first-line group and 35.0 months in the relapsed/refractory group (total = 47.1 months). Median progress-free survival in the groups was 22.0 months and 20.9 months, respectively, and median duration of response was 20.5 months and 26.5 months, respectively.

With regard to the new findings, “it is good to see the responses with ibrutinib and venetoclax were deep and durable,” Dr. Epperla said. The combination treatment “provides a good alternative option for TP53-mutated MCL patients who are ineligible for CAR-T.”

Dr. Epperla added that the findings about the addition of ibrutinib could apply to newer-generation Bruton tyrosine kinase inhibitors that have relatively better safety profiles.

However, Dr. Epperla cautioned that the treatment needs to be weighed against the toxicity and cost of the regimen of ibrutinib and venetoclax for 2 years then single-agent ibrutinib until progression or unacceptable toxicity.

This news organization reported in 2023 that estimated net spending on ibrutinib per Medicare data increased by nearly half from 2014-2020, reaching $11,980 in 2020 vs. $7,787 for venetoclax.

Dr. Epperla also noted that “there are newer therapies that are emerging, such as T-cell-engaging bispecific antibodies, and they have shown promising results.”

In an interview, Brad S. Kahl, MD, a hematologist-oncologist at Washington University, St. Louis, said the improvement in outcomes are “modestly significant.”

Dr. Kahl, who is familiar with the study findings but didn’t take part in the research, said it is “worth adding the venetoclax, particularly in these biologically high risk patients with p53 mutations. Venetoclax is not FDA-approved, so insurance approval will need to be determined on a case-by-case basis. The combination is very expensive.”

Dr. Kahl agreed with Dr. Epperla that the findings could be extrapolated to other Bruton tyrosine kinase inhibitors.

The study was funded by Pharmacyclics, an AbbVie Company. Dr. Epperla disclosed relationships with BeiGene and Eli Lilly. Dr. Kahl reported ties with AstraZeneca, BeiGene, Abbvie, and Genentech.

Irisin levels in cerebrospinal fluid (CSF) are significantly lower among patients with Alzheimer’s disease, and levels positively correlate with amyloid beta 1-42 (Abeta42), increasing support for this emerging Alzheimer’s disease biomarker, according to investigators.

Irisin, a hormone released by muscles during physical exercise, also negatively correlated with Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) in female patients, pointing to a sex-specific disease phenomenon, reported by co-lead authors Manuela Dicarlo, PhD, and Patrizia Pignataro, MSc, of the University of Bari “A. Moro,” Bari, Italy, and colleagues.

Regular physical exercise can slow cognitive decline in individuals at risk for or with Alzheimer’s disease, and irisin appears to play a key role in this process, the investigators wrote in Annals of Neurology. Previous studies have shown that increased irisin levels in the brain are associated with improved cognitive function and reduced amyloid beta levels, suggesting the hormone’s potential as a biomarker and therapeutic target for Alzheimer’s disease.

“Based on the protective effect of irisin in Alzheimer’s disease shown in animal and cell models, the goal of the present study was to investigate the levels of irisin in the biological fluids of a large cohort of patients biologically characterized according to the amyloid/tau/neurodegeneration (ATN) scheme of the National Institute on Aging–Alzheimer’s Association (NIA-AA),” Dr. Dicarlo and colleagues wrote. “We aimed to understand whether there may be variations of irisin levels across the disease stages, identified through the ATN system.”
 

Lower Levels of Irisin Seen in Patients With Alzheimer’s Disease

The study included 82 patients with Alzheimer’s disease, 44 individuals with mild cognitive impairment (MCI), and 20 with subjective memory complaints (SMC). Participants underwent comprehensive assessments, including neurological and neuropsychological exams, nutritional evaluations, MRI scans, and routine lab tests. Cognitive impairment severity was measured using the CDR-SOB and other metrics.

Blood and CSF samples were collected from all patients, the latter via lumbar puncture. These samples were analyzed for irisin levels and known Alzheimer’s disease biomarkers, including Abeta42, total tau (t-tau), and hyperphosphorylated tau (p-tau).

Mean CSF irisin levels were significantly lower among patients with Alzheimer’s disease than those with SMC (0.80 vs 1.23 pg/mL; P < .0001), and among those with MCI vs SMC (0.95 vs 1.23 pg/mL; P = .046). Among patients with Alzheimer’s disease, irisin levels were significantly lower among women than men (0.70 vs 0.96 pg/mL; P = .031).

Further analyses revealed positive correlations between CSF irisin level and Abeta42 in both males (r = 0.262; P < 005) and females (r = 0.379; P < .001). Conversely, in female patients, a significant negative correlation was found between CSF irisin level and CDR-SOB score (r = −0.234; P < .05).

Although a negative trend was observed between CSF irisin and total tau (t-tau) in the overall patient population (r = −0.144; P = 0.082), and more notably in female patients (r = −0.189; P = 0.084), these results were not statistically significant.

Plasma irisin levels were not significantly correlated with any of the other biomarkers.
 

Clinical Implications

This study “verifies that irisin levels do have a relationship to the Alzheimer’s disease process,” said Dylan Wint, MD, director of Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas.

In a written comment, Dr. Wint speculated that measuring irisin levels could theoretically help individualize physical exercise routines designed to combat cognitive decline.

“For example, maybe someone who is exercising but has a low irisin level would need to change the type of exercise they’re doing in order to optimally protect their brain health,” he said. “Or maybe they won’t get the same benefits for brain health as someone whose irisin shoots up every time they walk a flight of stairs.”

Cleveland Clinic

It’s “near-impossible to tell,” however, if irisin will be employed in clinical trials or real-world practice, he added.

“I don’t see this being a highly useful serum biomarker for Alzheimer’s disease itself because other serum biomarkers are so far ahead and have more face validity,” Dr. Wint said.

The route of collection could also cause challenges.

“In the United States, CSF-based biomarkers can be a difficult sell, especially for serial testing,” Dr. Wint said. “But we have usable serum biomarkers for Alzheimer’s disease only because we have had CSF biomarkers against which to evaluate them. They may develop a way to evaluate this in the serum.”

Dr. Dicarlo and colleagues suggested that more work is needed to determine the ultimate value of irisin measurement.“The true ability of irisin to represent a biomarker of disease progression and severity remains to be further investigated,” they concluded. “However, our findings might offer interesting perspectives toward the potential role of irisin in the modulation of AD pathology and can guide the exploration of medication targeting the irisin system.”

The study was supported by Regione Puglia and CNR for Tecnopolo per la Medicina di Precisione, CIREMIC, the University of Bari, and Next Generation EU. The investigators and Dr. Wint disclosed no conflicts of interest.

Irisin levels in cerebrospinal fluid (CSF) are significantly lower among patients with Alzheimer’s disease, and levels positively correlate with amyloid beta 1-42 (Abeta42), increasing support for this emerging Alzheimer’s disease biomarker, according to investigators.

Irisin, a hormone released by muscles during physical exercise, also negatively correlated with Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) in female patients, pointing to a sex-specific disease phenomenon, reported by co-lead authors Manuela Dicarlo, PhD, and Patrizia Pignataro, MSc, of the University of Bari “A. Moro,” Bari, Italy, and colleagues.

Regular physical exercise can slow cognitive decline in individuals at risk for or with Alzheimer’s disease, and irisin appears to play a key role in this process, the investigators wrote in Annals of Neurology. Previous studies have shown that increased irisin levels in the brain are associated with improved cognitive function and reduced amyloid beta levels, suggesting the hormone’s potential as a biomarker and therapeutic target for Alzheimer’s disease.

“Based on the protective effect of irisin in Alzheimer’s disease shown in animal and cell models, the goal of the present study was to investigate the levels of irisin in the biological fluids of a large cohort of patients biologically characterized according to the amyloid/tau/neurodegeneration (ATN) scheme of the National Institute on Aging–Alzheimer’s Association (NIA-AA),” Dr. Dicarlo and colleagues wrote. “We aimed to understand whether there may be variations of irisin levels across the disease stages, identified through the ATN system.”
 

Lower Levels of Irisin Seen in Patients With Alzheimer’s Disease

The study included 82 patients with Alzheimer’s disease, 44 individuals with mild cognitive impairment (MCI), and 20 with subjective memory complaints (SMC). Participants underwent comprehensive assessments, including neurological and neuropsychological exams, nutritional evaluations, MRI scans, and routine lab tests. Cognitive impairment severity was measured using the CDR-SOB and other metrics.

Blood and CSF samples were collected from all patients, the latter via lumbar puncture. These samples were analyzed for irisin levels and known Alzheimer’s disease biomarkers, including Abeta42, total tau (t-tau), and hyperphosphorylated tau (p-tau).

Mean CSF irisin levels were significantly lower among patients with Alzheimer’s disease than those with SMC (0.80 vs 1.23 pg/mL; P < .0001), and among those with MCI vs SMC (0.95 vs 1.23 pg/mL; P = .046). Among patients with Alzheimer’s disease, irisin levels were significantly lower among women than men (0.70 vs 0.96 pg/mL; P = .031).

Further analyses revealed positive correlations between CSF irisin level and Abeta42 in both males (r = 0.262; P < 005) and females (r = 0.379; P < .001). Conversely, in female patients, a significant negative correlation was found between CSF irisin level and CDR-SOB score (r = −0.234; P < .05).

Although a negative trend was observed between CSF irisin and total tau (t-tau) in the overall patient population (r = −0.144; P = 0.082), and more notably in female patients (r = −0.189; P = 0.084), these results were not statistically significant.

Plasma irisin levels were not significantly correlated with any of the other biomarkers.
 

Clinical Implications

This study “verifies that irisin levels do have a relationship to the Alzheimer’s disease process,” said Dylan Wint, MD, director of Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas.

In a written comment, Dr. Wint speculated that measuring irisin levels could theoretically help individualize physical exercise routines designed to combat cognitive decline.

“For example, maybe someone who is exercising but has a low irisin level would need to change the type of exercise they’re doing in order to optimally protect their brain health,” he said. “Or maybe they won’t get the same benefits for brain health as someone whose irisin shoots up every time they walk a flight of stairs.”

Cleveland Clinic

It’s “near-impossible to tell,” however, if irisin will be employed in clinical trials or real-world practice, he added.

“I don’t see this being a highly useful serum biomarker for Alzheimer’s disease itself because other serum biomarkers are so far ahead and have more face validity,” Dr. Wint said.

The route of collection could also cause challenges.

“In the United States, CSF-based biomarkers can be a difficult sell, especially for serial testing,” Dr. Wint said. “But we have usable serum biomarkers for Alzheimer’s disease only because we have had CSF biomarkers against which to evaluate them. They may develop a way to evaluate this in the serum.”

Dr. Dicarlo and colleagues suggested that more work is needed to determine the ultimate value of irisin measurement.“The true ability of irisin to represent a biomarker of disease progression and severity remains to be further investigated,” they concluded. “However, our findings might offer interesting perspectives toward the potential role of irisin in the modulation of AD pathology and can guide the exploration of medication targeting the irisin system.”

The study was supported by Regione Puglia and CNR for Tecnopolo per la Medicina di Precisione, CIREMIC, the University of Bari, and Next Generation EU. The investigators and Dr. Wint disclosed no conflicts of interest.

Irisin levels in cerebrospinal fluid (CSF) are significantly lower among patients with Alzheimer’s disease, and levels positively correlate with amyloid beta 1-42 (Abeta42), increasing support for this emerging Alzheimer’s disease biomarker, according to investigators.

Irisin, a hormone released by muscles during physical exercise, also negatively correlated with Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) in female patients, pointing to a sex-specific disease phenomenon, reported by co-lead authors Manuela Dicarlo, PhD, and Patrizia Pignataro, MSc, of the University of Bari “A. Moro,” Bari, Italy, and colleagues.

Regular physical exercise can slow cognitive decline in individuals at risk for or with Alzheimer’s disease, and irisin appears to play a key role in this process, the investigators wrote in Annals of Neurology. Previous studies have shown that increased irisin levels in the brain are associated with improved cognitive function and reduced amyloid beta levels, suggesting the hormone’s potential as a biomarker and therapeutic target for Alzheimer’s disease.

“Based on the protective effect of irisin in Alzheimer’s disease shown in animal and cell models, the goal of the present study was to investigate the levels of irisin in the biological fluids of a large cohort of patients biologically characterized according to the amyloid/tau/neurodegeneration (ATN) scheme of the National Institute on Aging–Alzheimer’s Association (NIA-AA),” Dr. Dicarlo and colleagues wrote. “We aimed to understand whether there may be variations of irisin levels across the disease stages, identified through the ATN system.”
 

Lower Levels of Irisin Seen in Patients With Alzheimer’s Disease

The study included 82 patients with Alzheimer’s disease, 44 individuals with mild cognitive impairment (MCI), and 20 with subjective memory complaints (SMC). Participants underwent comprehensive assessments, including neurological and neuropsychological exams, nutritional evaluations, MRI scans, and routine lab tests. Cognitive impairment severity was measured using the CDR-SOB and other metrics.

Blood and CSF samples were collected from all patients, the latter via lumbar puncture. These samples were analyzed for irisin levels and known Alzheimer’s disease biomarkers, including Abeta42, total tau (t-tau), and hyperphosphorylated tau (p-tau).

Mean CSF irisin levels were significantly lower among patients with Alzheimer’s disease than those with SMC (0.80 vs 1.23 pg/mL; P < .0001), and among those with MCI vs SMC (0.95 vs 1.23 pg/mL; P = .046). Among patients with Alzheimer’s disease, irisin levels were significantly lower among women than men (0.70 vs 0.96 pg/mL; P = .031).

Further analyses revealed positive correlations between CSF irisin level and Abeta42 in both males (r = 0.262; P < 005) and females (r = 0.379; P < .001). Conversely, in female patients, a significant negative correlation was found between CSF irisin level and CDR-SOB score (r = −0.234; P < .05).

Although a negative trend was observed between CSF irisin and total tau (t-tau) in the overall patient population (r = −0.144; P = 0.082), and more notably in female patients (r = −0.189; P = 0.084), these results were not statistically significant.

Plasma irisin levels were not significantly correlated with any of the other biomarkers.
 

Clinical Implications

This study “verifies that irisin levels do have a relationship to the Alzheimer’s disease process,” said Dylan Wint, MD, director of Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas.

In a written comment, Dr. Wint speculated that measuring irisin levels could theoretically help individualize physical exercise routines designed to combat cognitive decline.

“For example, maybe someone who is exercising but has a low irisin level would need to change the type of exercise they’re doing in order to optimally protect their brain health,” he said. “Or maybe they won’t get the same benefits for brain health as someone whose irisin shoots up every time they walk a flight of stairs.”

Cleveland Clinic

It’s “near-impossible to tell,” however, if irisin will be employed in clinical trials or real-world practice, he added.

“I don’t see this being a highly useful serum biomarker for Alzheimer’s disease itself because other serum biomarkers are so far ahead and have more face validity,” Dr. Wint said.

The route of collection could also cause challenges.

“In the United States, CSF-based biomarkers can be a difficult sell, especially for serial testing,” Dr. Wint said. “But we have usable serum biomarkers for Alzheimer’s disease only because we have had CSF biomarkers against which to evaluate them. They may develop a way to evaluate this in the serum.”

Dr. Dicarlo and colleagues suggested that more work is needed to determine the ultimate value of irisin measurement.“The true ability of irisin to represent a biomarker of disease progression and severity remains to be further investigated,” they concluded. “However, our findings might offer interesting perspectives toward the potential role of irisin in the modulation of AD pathology and can guide the exploration of medication targeting the irisin system.”

The study was supported by Regione Puglia and CNR for Tecnopolo per la Medicina di Precisione, CIREMIC, the University of Bari, and Next Generation EU. The investigators and Dr. Wint disclosed no conflicts of interest.

PARIS — Allergic comorbidities such as asthma and rhinitis are common among pregnant women. During the 19th French-speaking Congress of Allergology, Dario Ebode, MD, otolaryngologist and cervicofacial surgeon at Hôpital de la Conception in Marseille, France, described gestational rhinitis and detailed its management.

A Hormonal Rhinitis

The prevalence of rhinitis during pregnancy ranges from 18% to 30%, whether it is pre-existing (eg, allergic or infectious) or newly diagnosed. About half of the cases of pre-existing rhinitis worsen during pregnancy, leading to gestational rhinitis, which has a prevalence of approximately 22%.

“The latter is characterized by its onset in the 2nd or 3rd trimester, a duration of > 6 weeks, an absence of associated allergic symptoms, and complete spontaneous resolution 2-3 weeks after delivery,” said Dr. Ebode.

Uncertainties about the pathophysiology of gestational rhinitis, a “hormonal rhinitis,” remain, he added. Beta-estradiol and progesterone hormones lead to an increase in H1 histamine receptors on epithelial and endothelial cells, which promotes the migration or degranulation of eosinophils.
 

Management

While gestational rhinitis is benign, its symptoms can still be bothersome and can be relieved. In addition to dietary and hygienic (nasal irrigation with large volumes) measures and allergen avoidance, local treatments include nasal corticosteroids, possibly combined with antihistamines, and systemic antihistamines. “During pregnancy, nasal corticosteroids, oral antihistamines [excluding azelastine hydrochloride before 10 weeks], and ipratropium bromide are allowed,” said Dr. Ebode. Regarding sprays that combine corticosteroids and antihistamines, the combination of mometasone furoate and olopatadine is possible but not the combination of azelastine hydrochloride and fluticasone propionate before 10 weeks.

Finally, oral vasoconstrictors (which are found in many over-the-counter medications) should be avoided, as should Kenacort (triamcinolone acetonide), “which also has no place in women outside of pregnancy due to an unfavorable risk-benefit balance in rhinitis,” said Dr. Ebode. Allergen immunotherapy plans should be postponed after delivery.

Dr. Ebode reported a financial relationship with Zambon.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

PARIS — Allergic comorbidities such as asthma and rhinitis are common among pregnant women. During the 19th French-speaking Congress of Allergology, Dario Ebode, MD, otolaryngologist and cervicofacial surgeon at Hôpital de la Conception in Marseille, France, described gestational rhinitis and detailed its management.

A Hormonal Rhinitis

The prevalence of rhinitis during pregnancy ranges from 18% to 30%, whether it is pre-existing (eg, allergic or infectious) or newly diagnosed. About half of the cases of pre-existing rhinitis worsen during pregnancy, leading to gestational rhinitis, which has a prevalence of approximately 22%.

“The latter is characterized by its onset in the 2nd or 3rd trimester, a duration of > 6 weeks, an absence of associated allergic symptoms, and complete spontaneous resolution 2-3 weeks after delivery,” said Dr. Ebode.

Uncertainties about the pathophysiology of gestational rhinitis, a “hormonal rhinitis,” remain, he added. Beta-estradiol and progesterone hormones lead to an increase in H1 histamine receptors on epithelial and endothelial cells, which promotes the migration or degranulation of eosinophils.
 

Management

While gestational rhinitis is benign, its symptoms can still be bothersome and can be relieved. In addition to dietary and hygienic (nasal irrigation with large volumes) measures and allergen avoidance, local treatments include nasal corticosteroids, possibly combined with antihistamines, and systemic antihistamines. “During pregnancy, nasal corticosteroids, oral antihistamines [excluding azelastine hydrochloride before 10 weeks], and ipratropium bromide are allowed,” said Dr. Ebode. Regarding sprays that combine corticosteroids and antihistamines, the combination of mometasone furoate and olopatadine is possible but not the combination of azelastine hydrochloride and fluticasone propionate before 10 weeks.

Finally, oral vasoconstrictors (which are found in many over-the-counter medications) should be avoided, as should Kenacort (triamcinolone acetonide), “which also has no place in women outside of pregnancy due to an unfavorable risk-benefit balance in rhinitis,” said Dr. Ebode. Allergen immunotherapy plans should be postponed after delivery.

Dr. Ebode reported a financial relationship with Zambon.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

PARIS — Allergic comorbidities such as asthma and rhinitis are common among pregnant women. During the 19th French-speaking Congress of Allergology, Dario Ebode, MD, otolaryngologist and cervicofacial surgeon at Hôpital de la Conception in Marseille, France, described gestational rhinitis and detailed its management.

A Hormonal Rhinitis

The prevalence of rhinitis during pregnancy ranges from 18% to 30%, whether it is pre-existing (eg, allergic or infectious) or newly diagnosed. About half of the cases of pre-existing rhinitis worsen during pregnancy, leading to gestational rhinitis, which has a prevalence of approximately 22%.

“The latter is characterized by its onset in the 2nd or 3rd trimester, a duration of > 6 weeks, an absence of associated allergic symptoms, and complete spontaneous resolution 2-3 weeks after delivery,” said Dr. Ebode.

Uncertainties about the pathophysiology of gestational rhinitis, a “hormonal rhinitis,” remain, he added. Beta-estradiol and progesterone hormones lead to an increase in H1 histamine receptors on epithelial and endothelial cells, which promotes the migration or degranulation of eosinophils.
 

Management

While gestational rhinitis is benign, its symptoms can still be bothersome and can be relieved. In addition to dietary and hygienic (nasal irrigation with large volumes) measures and allergen avoidance, local treatments include nasal corticosteroids, possibly combined with antihistamines, and systemic antihistamines. “During pregnancy, nasal corticosteroids, oral antihistamines [excluding azelastine hydrochloride before 10 weeks], and ipratropium bromide are allowed,” said Dr. Ebode. Regarding sprays that combine corticosteroids and antihistamines, the combination of mometasone furoate and olopatadine is possible but not the combination of azelastine hydrochloride and fluticasone propionate before 10 weeks.

Finally, oral vasoconstrictors (which are found in many over-the-counter medications) should be avoided, as should Kenacort (triamcinolone acetonide), “which also has no place in women outside of pregnancy due to an unfavorable risk-benefit balance in rhinitis,” said Dr. Ebode. Allergen immunotherapy plans should be postponed after delivery.

Dr. Ebode reported a financial relationship with Zambon.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

When Ezra Spier was diagnosed with long COVID in late 2022, his main symptom, postexertional malaise, caused fatigue so severe that it forced him to quit his job as a technology entrepreneur. Since then, it’s been a tough road for Spier, 37, who said he wouldn’t wish his hellish condition on anyone. 

Last spring, he enrolled in a clinical trial of a new long COVID therapy at Stanford University, and he’s about to start another at the University of California, San Francisco. 

For Spier, who lives in Oakland, California, being part of the clinical trials connected him with people dealing with similar health issues while also moving the needle toward better treatments for everyone. Yet many potential participants are unaware that these clinical trials exist. Clinical trial researchers also express frustration over the challenge of enrolling participants.

That’s why Spier created a new website to help match long COVID patients with clinical trials that can help.

“I wanted a way to make long COVID clinical trials more accessible to the general public,” he said. Spier’s website, aptly named Long Covid Studies, launched in March. The site already includes details from about 550 trials globally and, in the future, will include many more.
 

It’s Not the Number of Studies, It’s Navigating Them

In all, nearly 9300 long COVID trials are listed on ClinicalTrials.gov. But many patients find the site difficult to navigate, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City. He said Spier’s website helps make trials easier for patients to manage in ways that remove the enrollment challenges.

“Ezra’s platform pulls data from ClinicalTrials.gov and puts it into a space that’s much easier for patients to manage,” said Dr. Putrino. The site only includes the most relevant information, such as the study location, eligibility, and purpose and how to sign up. 

Another of Spier’s goals is to make the process easier for patients who are already marginalized and often excluded from the healthcare system. Long COVID disproportionately impacts people in minority ethnic groups and women, as well as those who are impoverished or live in rural areas. 

According to the National Institutes of Health (NIH), 1 in 4 patients with severe long COVID-19 are Black or Hispanic whereas only 1 in 7 are White. Yet participation by White persons in clinical trials is much higher overall: 77% of participants are White, compared with only 14% for Black persons and 15% for Hispanic persons. Without more balanced representation, research becomes skewed and less accurate, said Grace McComsey, MD, who leads one of the 15 nationwide long COVID centers funded by the federal RECOVER (Researching COVID to Enhance Recovery) Initiative in Cleveland. 

Websites that are easier for the layperson to access would allow for wider participation, said McComsey.
 

Too Many Barriers to Entry

A study published in the Journal of Applied Gerontology found that transportation plays an outsized role in influencing study participation, which may also lead to less diverse participation.

Decentralized trials — in which participants receive therapy at home — also make enrolling in clinical trials easier for marginalized patients and those too sick to make it to a research center, said Dr. Putrino. Research published recently in The American Journal of Medicine demonstrated that for many patients, remote studies are the future of COVID research. The study, focusing on the efficacy of Paxlovid, recruited patients living in the 48 contiguous US states. Participation was entirely remote. 

“We need to have more consideration for bedbound and housebound patients in our research,” said Dr. Putrino. “Some people don’t have the ability to show up to a prestigious university to take part in an academic trial.”

Dr. Putrino and colleagues at Yale School of Medicine’s Yale COVID Recovery Study plan to release a paper in the near future on the methodology for running decentralized or remote studies that could provide guidance for researchers elsewhere. 

Decentralized studies serve a larger audience, but they’re also more expensive and cost has plagued long COVID research from the start, said Michael Peluso, MD, an assistant research professor of infectious medicine at UCSF School of Medicine, University of California, San Francisco. 

“You need to have a staff in place that’s trained to do home visits in order to conduct remote trials,” Dr. Peluso said, adding that his biggest challenge has been connecting patients to appropriate clinical trials. 

Individual eligibility has been an ongoing issue. For example, Dr. Peluso’s current trials are testing monoclonal antibodies — antibodies produced by cloning unique white blood cells to target viral persistence, which is thought to be a cause of long COVID. Only patients who were infected with certain variants of acute COVID are eligible because of the antibodies needed to target SARS-CoV-2 spike proteins. 

“This can lead to a lot of frustration among patients who might think they can participate, but aren’t eligible,” said Dr. Peluso.
 

Long Fight for Better Long COVID Research

For Spier, one of the hardest parts of his health issues and lack of energy is that they have sharply curtailed his social interactions with friends and colleagues. 

He has channeled his energies into researching new treatments that could potentially improve his symptoms. That research is partly what drove him to create the Long Covid Studies website.

His goal is still to help others with long COVID find trials that can improve their symptoms as well. The more people who participate, the closer scientists will come to providing effective treatments for everyone, he said.

“For all my frustrations, we’re still at the forefront of science globally,” he said. “And if we have the level of funding the NIH is equipped to provide, we can show the world what’s possible with long COVID research.”

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

When Ezra Spier was diagnosed with long COVID in late 2022, his main symptom, postexertional malaise, caused fatigue so severe that it forced him to quit his job as a technology entrepreneur. Since then, it’s been a tough road for Spier, 37, who said he wouldn’t wish his hellish condition on anyone. 

Last spring, he enrolled in a clinical trial of a new long COVID therapy at Stanford University, and he’s about to start another at the University of California, San Francisco. 

For Spier, who lives in Oakland, California, being part of the clinical trials connected him with people dealing with similar health issues while also moving the needle toward better treatments for everyone. Yet many potential participants are unaware that these clinical trials exist. Clinical trial researchers also express frustration over the challenge of enrolling participants.

That’s why Spier created a new website to help match long COVID patients with clinical trials that can help.

“I wanted a way to make long COVID clinical trials more accessible to the general public,” he said. Spier’s website, aptly named Long Covid Studies, launched in March. The site already includes details from about 550 trials globally and, in the future, will include many more.
 

It’s Not the Number of Studies, It’s Navigating Them

In all, nearly 9300 long COVID trials are listed on ClinicalTrials.gov. But many patients find the site difficult to navigate, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City. He said Spier’s website helps make trials easier for patients to manage in ways that remove the enrollment challenges.

“Ezra’s platform pulls data from ClinicalTrials.gov and puts it into a space that’s much easier for patients to manage,” said Dr. Putrino. The site only includes the most relevant information, such as the study location, eligibility, and purpose and how to sign up. 

Another of Spier’s goals is to make the process easier for patients who are already marginalized and often excluded from the healthcare system. Long COVID disproportionately impacts people in minority ethnic groups and women, as well as those who are impoverished or live in rural areas. 

According to the National Institutes of Health (NIH), 1 in 4 patients with severe long COVID-19 are Black or Hispanic whereas only 1 in 7 are White. Yet participation by White persons in clinical trials is much higher overall: 77% of participants are White, compared with only 14% for Black persons and 15% for Hispanic persons. Without more balanced representation, research becomes skewed and less accurate, said Grace McComsey, MD, who leads one of the 15 nationwide long COVID centers funded by the federal RECOVER (Researching COVID to Enhance Recovery) Initiative in Cleveland. 

Websites that are easier for the layperson to access would allow for wider participation, said McComsey.
 

Too Many Barriers to Entry

A study published in the Journal of Applied Gerontology found that transportation plays an outsized role in influencing study participation, which may also lead to less diverse participation.

Decentralized trials — in which participants receive therapy at home — also make enrolling in clinical trials easier for marginalized patients and those too sick to make it to a research center, said Dr. Putrino. Research published recently in The American Journal of Medicine demonstrated that for many patients, remote studies are the future of COVID research. The study, focusing on the efficacy of Paxlovid, recruited patients living in the 48 contiguous US states. Participation was entirely remote. 

“We need to have more consideration for bedbound and housebound patients in our research,” said Dr. Putrino. “Some people don’t have the ability to show up to a prestigious university to take part in an academic trial.”

Dr. Putrino and colleagues at Yale School of Medicine’s Yale COVID Recovery Study plan to release a paper in the near future on the methodology for running decentralized or remote studies that could provide guidance for researchers elsewhere. 

Decentralized studies serve a larger audience, but they’re also more expensive and cost has plagued long COVID research from the start, said Michael Peluso, MD, an assistant research professor of infectious medicine at UCSF School of Medicine, University of California, San Francisco. 

“You need to have a staff in place that’s trained to do home visits in order to conduct remote trials,” Dr. Peluso said, adding that his biggest challenge has been connecting patients to appropriate clinical trials. 

Individual eligibility has been an ongoing issue. For example, Dr. Peluso’s current trials are testing monoclonal antibodies — antibodies produced by cloning unique white blood cells to target viral persistence, which is thought to be a cause of long COVID. Only patients who were infected with certain variants of acute COVID are eligible because of the antibodies needed to target SARS-CoV-2 spike proteins. 

“This can lead to a lot of frustration among patients who might think they can participate, but aren’t eligible,” said Dr. Peluso.
 

Long Fight for Better Long COVID Research

For Spier, one of the hardest parts of his health issues and lack of energy is that they have sharply curtailed his social interactions with friends and colleagues. 

He has channeled his energies into researching new treatments that could potentially improve his symptoms. That research is partly what drove him to create the Long Covid Studies website.

His goal is still to help others with long COVID find trials that can improve their symptoms as well. The more people who participate, the closer scientists will come to providing effective treatments for everyone, he said.

“For all my frustrations, we’re still at the forefront of science globally,” he said. “And if we have the level of funding the NIH is equipped to provide, we can show the world what’s possible with long COVID research.”

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

When Ezra Spier was diagnosed with long COVID in late 2022, his main symptom, postexertional malaise, caused fatigue so severe that it forced him to quit his job as a technology entrepreneur. Since then, it’s been a tough road for Spier, 37, who said he wouldn’t wish his hellish condition on anyone. 

Last spring, he enrolled in a clinical trial of a new long COVID therapy at Stanford University, and he’s about to start another at the University of California, San Francisco. 

For Spier, who lives in Oakland, California, being part of the clinical trials connected him with people dealing with similar health issues while also moving the needle toward better treatments for everyone. Yet many potential participants are unaware that these clinical trials exist. Clinical trial researchers also express frustration over the challenge of enrolling participants.

That’s why Spier created a new website to help match long COVID patients with clinical trials that can help.

“I wanted a way to make long COVID clinical trials more accessible to the general public,” he said. Spier’s website, aptly named Long Covid Studies, launched in March. The site already includes details from about 550 trials globally and, in the future, will include many more.
 

It’s Not the Number of Studies, It’s Navigating Them

In all, nearly 9300 long COVID trials are listed on ClinicalTrials.gov. But many patients find the site difficult to navigate, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City. He said Spier’s website helps make trials easier for patients to manage in ways that remove the enrollment challenges.

“Ezra’s platform pulls data from ClinicalTrials.gov and puts it into a space that’s much easier for patients to manage,” said Dr. Putrino. The site only includes the most relevant information, such as the study location, eligibility, and purpose and how to sign up. 

Another of Spier’s goals is to make the process easier for patients who are already marginalized and often excluded from the healthcare system. Long COVID disproportionately impacts people in minority ethnic groups and women, as well as those who are impoverished or live in rural areas. 

According to the National Institutes of Health (NIH), 1 in 4 patients with severe long COVID-19 are Black or Hispanic whereas only 1 in 7 are White. Yet participation by White persons in clinical trials is much higher overall: 77% of participants are White, compared with only 14% for Black persons and 15% for Hispanic persons. Without more balanced representation, research becomes skewed and less accurate, said Grace McComsey, MD, who leads one of the 15 nationwide long COVID centers funded by the federal RECOVER (Researching COVID to Enhance Recovery) Initiative in Cleveland. 

Websites that are easier for the layperson to access would allow for wider participation, said McComsey.
 

Too Many Barriers to Entry

A study published in the Journal of Applied Gerontology found that transportation plays an outsized role in influencing study participation, which may also lead to less diverse participation.

Decentralized trials — in which participants receive therapy at home — also make enrolling in clinical trials easier for marginalized patients and those too sick to make it to a research center, said Dr. Putrino. Research published recently in The American Journal of Medicine demonstrated that for many patients, remote studies are the future of COVID research. The study, focusing on the efficacy of Paxlovid, recruited patients living in the 48 contiguous US states. Participation was entirely remote. 

“We need to have more consideration for bedbound and housebound patients in our research,” said Dr. Putrino. “Some people don’t have the ability to show up to a prestigious university to take part in an academic trial.”

Dr. Putrino and colleagues at Yale School of Medicine’s Yale COVID Recovery Study plan to release a paper in the near future on the methodology for running decentralized or remote studies that could provide guidance for researchers elsewhere. 

Decentralized studies serve a larger audience, but they’re also more expensive and cost has plagued long COVID research from the start, said Michael Peluso, MD, an assistant research professor of infectious medicine at UCSF School of Medicine, University of California, San Francisco. 

“You need to have a staff in place that’s trained to do home visits in order to conduct remote trials,” Dr. Peluso said, adding that his biggest challenge has been connecting patients to appropriate clinical trials. 

Individual eligibility has been an ongoing issue. For example, Dr. Peluso’s current trials are testing monoclonal antibodies — antibodies produced by cloning unique white blood cells to target viral persistence, which is thought to be a cause of long COVID. Only patients who were infected with certain variants of acute COVID are eligible because of the antibodies needed to target SARS-CoV-2 spike proteins. 

“This can lead to a lot of frustration among patients who might think they can participate, but aren’t eligible,” said Dr. Peluso.
 

Long Fight for Better Long COVID Research

For Spier, one of the hardest parts of his health issues and lack of energy is that they have sharply curtailed his social interactions with friends and colleagues. 

He has channeled his energies into researching new treatments that could potentially improve his symptoms. That research is partly what drove him to create the Long Covid Studies website.

His goal is still to help others with long COVID find trials that can improve their symptoms as well. The more people who participate, the closer scientists will come to providing effective treatments for everyone, he said.

“For all my frustrations, we’re still at the forefront of science globally,” he said. “And if we have the level of funding the NIH is equipped to provide, we can show the world what’s possible with long COVID research.”

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

In just 4 years, there’s been a significant evolution in the profile of pediatric and young adult patients who’ve taken the chimeric antigen receptor (CAR) T-cell immunotherapy known as tisagenlecleucel (Kymriah) for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), a new industry-funded study finds.

It’s becoming more common for patients with less severe disease to undergo the treatment, often bypassing hematopoietic stem cell transplantation (HSCT), and survival is on the rise.

From 2018 to 2022, the percentage of patients in an international cohort who had disease burden of ≥50% fell from 18% to 4%, researchers reported at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Median relapse-free survival in patients who didn’t undergo post-infusion HSCT grew from 18 months in 2018 to 27 months in 2020. It was not estimable in 2021.

“This introduction of the therapy is changing the treatment landscape of how we look at refractory B-ALL, where the standard of care previously would be to proceed to transplant. This therapy is actually reducing the use of transplant, which has lots of morbidity and mortality associated with it,” Texas Children’s Cancer Center hematologist-oncologist Rayne H. Rouce, MD, who led the study, said in an interview.

Tisagenlecleucel received Food and Drug Administration approval in 2017, said Nirali N. Shah, MD, MHSc, head of the Pediatric Oncology Branch’s Hematologic Malignancies Section at the National Cancer Institute, in an interview. Dr. Shah is familiar with the study findings but didn’t take part in the research.

Remission rates have been around 60%-70%, Dr. Shah said, although that rate is “likely higher” now because of gains in experience and improvement in disease burden prior to therapy. 

The new findings fill a knowledge gap about real-world outcomes since a lot of the prior data was based on investigational CAR T-cell products, she said.

The noninterventional, prospective, longitudinal study, funded by tisagenlecleucel manufacturer Novartis, tracked 974 patients up to age 25 who received tisagenlecleucel in the United States, Canada, Korea, and Taiwan.

The study found that between 2018 and 2022:

• The percentage of patients who received treatment while in morphological complete remission grew from 34% to 51%.
• The percentages who were in third or greater relapse fell from 14% to 2%.
• The percentages undergoing ≥1 HSCT before tisagenlecleucel infusion fell from 37% to 15%.
• Overall, 34.5% of 911 patients received post-infusion HSCT.

In the big picture, the findings suggest that the therapy can be considered more than “a last resort for patients in a second or greater relapse or who are refractory,” Dr. Rouce said. By offering CAR T-cell therapy to earlier-stage patients, she said, “when they’re less sick, when they have less comorbidities, and when their organs are functioning better, we could potentially save them from having to go on to a transplant.”

Dr. Shah said the findings indicate that “a substantial number of patients are surviving. It’s remarkable actually. Prior to tisagenlecleucel, patients had dismal outcomes from standard chemotherapy.”

She added that the study suggests “providers are getting much more comfortable with getting their patients in the best shape prior to getting CAR T-cell therapy. Outcomes are improving as providers expand the use of CAR T-cell therapy to patients who are less heavily pretreated and have lower disease burden.”

Moving forward, “at some point there will likely be a plateau in terms of how good the outcomes can be.” And there will be discussion of the role of HSCT.

“We’ll figure out some of the nuances about which patients need transplants and which can avoid them. But curative potential is growing. With or without transplant, this is ultimately going to lead to a much higher fraction of patients being cured who previously would not have been cured,” she said. “That’s the bottom line.”

As for adverse effects, Dr. Shah said “disease burden has a pretty direct relationship with side effects and toxicities. If you have more disease, you have more severe side effects.”

Reducing disease burden will reduce side effects, she said. Also, “we’re getting a lot better at managing these toxicities. Eliminating some of the more toxic chemotherapy through earlier use of CAR T-cells in chemotherapy-refractory patients may well help reduce therapy burden and improve long-term survival outcomes, she added.

As for cost, drugs.com reports that the therapy runs to more than $612,000 per infusion. But Dr. Shah said insurers are covering the treatment. She added that there are efforts to expand the indication so CAR T-cell therapy can be used earlier in patients who are chemotherapy-refractory.

Novartis funded the study. Dr. Shah discloses ties with Lentigen, VOR, and CARGO, ImmunoACT, and Sobi. Dr. Rouce reports relationships with Pfizer and Novartis.

In just 4 years, there’s been a significant evolution in the profile of pediatric and young adult patients who’ve taken the chimeric antigen receptor (CAR) T-cell immunotherapy known as tisagenlecleucel (Kymriah) for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), a new industry-funded study finds.

It’s becoming more common for patients with less severe disease to undergo the treatment, often bypassing hematopoietic stem cell transplantation (HSCT), and survival is on the rise.

From 2018 to 2022, the percentage of patients in an international cohort who had disease burden of ≥50% fell from 18% to 4%, researchers reported at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Median relapse-free survival in patients who didn’t undergo post-infusion HSCT grew from 18 months in 2018 to 27 months in 2020. It was not estimable in 2021.

“This introduction of the therapy is changing the treatment landscape of how we look at refractory B-ALL, where the standard of care previously would be to proceed to transplant. This therapy is actually reducing the use of transplant, which has lots of morbidity and mortality associated with it,” Texas Children’s Cancer Center hematologist-oncologist Rayne H. Rouce, MD, who led the study, said in an interview.

Tisagenlecleucel received Food and Drug Administration approval in 2017, said Nirali N. Shah, MD, MHSc, head of the Pediatric Oncology Branch’s Hematologic Malignancies Section at the National Cancer Institute, in an interview. Dr. Shah is familiar with the study findings but didn’t take part in the research.

Remission rates have been around 60%-70%, Dr. Shah said, although that rate is “likely higher” now because of gains in experience and improvement in disease burden prior to therapy. 

The new findings fill a knowledge gap about real-world outcomes since a lot of the prior data was based on investigational CAR T-cell products, she said.

The noninterventional, prospective, longitudinal study, funded by tisagenlecleucel manufacturer Novartis, tracked 974 patients up to age 25 who received tisagenlecleucel in the United States, Canada, Korea, and Taiwan.

The study found that between 2018 and 2022:

• The percentage of patients who received treatment while in morphological complete remission grew from 34% to 51%.
• The percentages who were in third or greater relapse fell from 14% to 2%.
• The percentages undergoing ≥1 HSCT before tisagenlecleucel infusion fell from 37% to 15%.
• Overall, 34.5% of 911 patients received post-infusion HSCT.

In the big picture, the findings suggest that the therapy can be considered more than “a last resort for patients in a second or greater relapse or who are refractory,” Dr. Rouce said. By offering CAR T-cell therapy to earlier-stage patients, she said, “when they’re less sick, when they have less comorbidities, and when their organs are functioning better, we could potentially save them from having to go on to a transplant.”

Dr. Shah said the findings indicate that “a substantial number of patients are surviving. It’s remarkable actually. Prior to tisagenlecleucel, patients had dismal outcomes from standard chemotherapy.”

She added that the study suggests “providers are getting much more comfortable with getting their patients in the best shape prior to getting CAR T-cell therapy. Outcomes are improving as providers expand the use of CAR T-cell therapy to patients who are less heavily pretreated and have lower disease burden.”

Moving forward, “at some point there will likely be a plateau in terms of how good the outcomes can be.” And there will be discussion of the role of HSCT.

“We’ll figure out some of the nuances about which patients need transplants and which can avoid them. But curative potential is growing. With or without transplant, this is ultimately going to lead to a much higher fraction of patients being cured who previously would not have been cured,” she said. “That’s the bottom line.”

As for adverse effects, Dr. Shah said “disease burden has a pretty direct relationship with side effects and toxicities. If you have more disease, you have more severe side effects.”

Reducing disease burden will reduce side effects, she said. Also, “we’re getting a lot better at managing these toxicities. Eliminating some of the more toxic chemotherapy through earlier use of CAR T-cells in chemotherapy-refractory patients may well help reduce therapy burden and improve long-term survival outcomes, she added.

As for cost, drugs.com reports that the therapy runs to more than $612,000 per infusion. But Dr. Shah said insurers are covering the treatment. She added that there are efforts to expand the indication so CAR T-cell therapy can be used earlier in patients who are chemotherapy-refractory.

Novartis funded the study. Dr. Shah discloses ties with Lentigen, VOR, and CARGO, ImmunoACT, and Sobi. Dr. Rouce reports relationships with Pfizer and Novartis.

In just 4 years, there’s been a significant evolution in the profile of pediatric and young adult patients who’ve taken the chimeric antigen receptor (CAR) T-cell immunotherapy known as tisagenlecleucel (Kymriah) for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), a new industry-funded study finds.

It’s becoming more common for patients with less severe disease to undergo the treatment, often bypassing hematopoietic stem cell transplantation (HSCT), and survival is on the rise.

From 2018 to 2022, the percentage of patients in an international cohort who had disease burden of ≥50% fell from 18% to 4%, researchers reported at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Median relapse-free survival in patients who didn’t undergo post-infusion HSCT grew from 18 months in 2018 to 27 months in 2020. It was not estimable in 2021.

“This introduction of the therapy is changing the treatment landscape of how we look at refractory B-ALL, where the standard of care previously would be to proceed to transplant. This therapy is actually reducing the use of transplant, which has lots of morbidity and mortality associated with it,” Texas Children’s Cancer Center hematologist-oncologist Rayne H. Rouce, MD, who led the study, said in an interview.

Tisagenlecleucel received Food and Drug Administration approval in 2017, said Nirali N. Shah, MD, MHSc, head of the Pediatric Oncology Branch’s Hematologic Malignancies Section at the National Cancer Institute, in an interview. Dr. Shah is familiar with the study findings but didn’t take part in the research.

Remission rates have been around 60%-70%, Dr. Shah said, although that rate is “likely higher” now because of gains in experience and improvement in disease burden prior to therapy. 

The new findings fill a knowledge gap about real-world outcomes since a lot of the prior data was based on investigational CAR T-cell products, she said.

The noninterventional, prospective, longitudinal study, funded by tisagenlecleucel manufacturer Novartis, tracked 974 patients up to age 25 who received tisagenlecleucel in the United States, Canada, Korea, and Taiwan.

The study found that between 2018 and 2022:

• The percentage of patients who received treatment while in morphological complete remission grew from 34% to 51%.
• The percentages who were in third or greater relapse fell from 14% to 2%.
• The percentages undergoing ≥1 HSCT before tisagenlecleucel infusion fell from 37% to 15%.
• Overall, 34.5% of 911 patients received post-infusion HSCT.

In the big picture, the findings suggest that the therapy can be considered more than “a last resort for patients in a second or greater relapse or who are refractory,” Dr. Rouce said. By offering CAR T-cell therapy to earlier-stage patients, she said, “when they’re less sick, when they have less comorbidities, and when their organs are functioning better, we could potentially save them from having to go on to a transplant.”

Dr. Shah said the findings indicate that “a substantial number of patients are surviving. It’s remarkable actually. Prior to tisagenlecleucel, patients had dismal outcomes from standard chemotherapy.”

She added that the study suggests “providers are getting much more comfortable with getting their patients in the best shape prior to getting CAR T-cell therapy. Outcomes are improving as providers expand the use of CAR T-cell therapy to patients who are less heavily pretreated and have lower disease burden.”

Moving forward, “at some point there will likely be a plateau in terms of how good the outcomes can be.” And there will be discussion of the role of HSCT.

“We’ll figure out some of the nuances about which patients need transplants and which can avoid them. But curative potential is growing. With or without transplant, this is ultimately going to lead to a much higher fraction of patients being cured who previously would not have been cured,” she said. “That’s the bottom line.”

As for adverse effects, Dr. Shah said “disease burden has a pretty direct relationship with side effects and toxicities. If you have more disease, you have more severe side effects.”

Reducing disease burden will reduce side effects, she said. Also, “we’re getting a lot better at managing these toxicities. Eliminating some of the more toxic chemotherapy through earlier use of CAR T-cells in chemotherapy-refractory patients may well help reduce therapy burden and improve long-term survival outcomes, she added.

As for cost, drugs.com reports that the therapy runs to more than $612,000 per infusion. But Dr. Shah said insurers are covering the treatment. She added that there are efforts to expand the indication so CAR T-cell therapy can be used earlier in patients who are chemotherapy-refractory.

Novartis funded the study. Dr. Shah discloses ties with Lentigen, VOR, and CARGO, ImmunoACT, and Sobi. Dr. Rouce reports relationships with Pfizer and Novartis.

Non-respiratory symptoms including poor sleep, fatigue, pain, anxiety, and depressive symptoms were prevalent among adults with cystic fibrosis (AwCF) and persisted after 1 year of follow-up, based on data from more than 200 individuals in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

“People with cystic fibrosis have qualitatively reported burden from extrapulmonary symptoms that were not being addressed by their health care providers; this is the first study to examine these symptoms concurrently in a large sample over time,” said lead author Kristin A. Riekert, PhD, of Johns Hopkins University, Baltimore, in an interview.

Previous cross-sectional studies have shown a high prevalence of poor sleep quality, fatigue, pain, depression, and anxiety among AwCF, but longitudinal data showing the persistence of symptoms are lacking, Dr. Riekert and colleagues noted in their abstract.
 

Sleep Quality, Anxiety, and Other Assessments

The researchers recruited a total of 236 AwCF aged 18 years and older from two cystic fibrosis (CF) centers between April 2021 and August 2022. They examined the prevalence of poor sleep quality, fatigue pain, depression, and anxiety in AwCF on the basis of five assessments: At baseline and at 3, 6, 9, and 12 months.

Participants were assessed via an online survey using the Fatigue Severity Scale (cutoff, > 4), Pittsburgh Sleep Quality Index (cutoff, > 5), Patient Health Questionnaire (cutoff, > 9), Generalized Anxiety Disorder (cutoff, > 9), and PROMIS Pain Intensity (cutoff, > 50 T score). Chronic symptoms were defined as positive scores on four or more assessments for individuals who completed four or five time-point assessments. The mean age of the participants was 37 years, 52% were women, 95% were non-Hispanic White, and 86% had been prescribed CF modulator therapy.

At 12 months, 62% of participants reported poor sleep, and 34% reported fatigue. In addition, 17% reported depressive symptoms, 14% reported anxiety symptoms, and 7% reported pain at 12 months.

Overall, 49% of participants met the criteria for chronic poor sleep quality, and 29% met the criteria for chronic fatigue, with positive assessments at four or more time points over the course of a year. In addition, 40%, 30%, and 18% of participants reported taking medication in the past 7 days for pain, mental health, and sleep, respectively.

The findings suggest that patients with CF might benefit from routine assessments of non-pulmonary symptoms in clinical care and from access to health care providers, including mental health professionals, to address non-pulmonary concerns, the researchers wrote in their abstract.

“We delayed starting the study until elexacaftor/tezacaftor/ivacaftor (ETI) was FDA-approved because there was an assumption that people with CF would have less fatigue because of respiratory improvements from ETI,” Dr. Riekert told this news organization. “Instead, the prevalence of fatigue and poor sleep quality was higher and more chronic than we had anticipated,” she noted.

However, “we were pleasantly surprised that depression and anxiety, while still prevalent, were less prevalent and chronic than previously reported,” Dr. Riekert said in an interview. “We attribute this to the CF Foundation’s mental health initiative that has increased the frequency of annual screening for depression and anxiety and provided resources to help people with cystic fibrosis obtain mental health services,” she said.

The study findings suggest that clinicians should assess people with CF for chronic fatigue and poor sleep along with depression and anxiety and provide treatment or referral, Dr. Riekert said. “For example, cognitive behavioral therapy can effectively treat all the symptoms that were measured in our study,” she noted.

Limitations of the study include the lack of data on how the non-respiratory symptoms interact with respiratory symptoms or pulmonary exacerbations, said Dr. Riekert. “While we assessed these symptoms five times, it was for a year; longer-term follow-up seems merited given our findings,” she said. In addition, “we need to study approaches to make cognitive behavioral therapy and other therapy more accessible for people with cystic fibrosis,” Dr. Riekert said.
 

Targeting Non-Pulmonary Dimensions of CF Care

The current study highlights an aspect of quality of life that is often forgotten when managing adults with CF and may affect their well-being despite effective therapy to improve function and prolong life, said Wissam Chatila, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

The high incidence of poor sleep, fatigue, depression, and anxiety seen in the current study was “somewhat surprising,” Dr. Chatila said. Also somewhat surprising was the chronicity of the symptoms considering the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (designed to correct the malfunctioning protein made by the CFTR gene) that have changed the face of CF, he noted.

However, recent growth in the number of adult patients with CF (more than 50% in certain countries) has led to a change in pathologies that physicians have to manage, and the current study addresses some of the emerging pathologies, said Dr. Chatila.

“Beyond demonstrating survival data from registries and other epidemiologic studies, this study sheds light on the need to address patient-reported outcomes that may or may not be directly related to the pulmonary and GI effects of the CFTR modulators,” he said. “Recognizing the extent of the dysfunction that many CF patients continue to suffer from will eventually lead to identifying factors that contribute to poor outcomes and the mechanisms involved,” he added.

Overall, the current study illustrates the potential benefits of offering personalized medicine to adults with CF that improves not only their physical function but also their mental health, Dr. Chatila said.

The study was funded by the Cystic Fibrosis Foundation. Dr. Riekert had no financial conflicts to disclose. Dr. Chatila had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Non-respiratory symptoms including poor sleep, fatigue, pain, anxiety, and depressive symptoms were prevalent among adults with cystic fibrosis (AwCF) and persisted after 1 year of follow-up, based on data from more than 200 individuals in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

“People with cystic fibrosis have qualitatively reported burden from extrapulmonary symptoms that were not being addressed by their health care providers; this is the first study to examine these symptoms concurrently in a large sample over time,” said lead author Kristin A. Riekert, PhD, of Johns Hopkins University, Baltimore, in an interview.

Previous cross-sectional studies have shown a high prevalence of poor sleep quality, fatigue, pain, depression, and anxiety among AwCF, but longitudinal data showing the persistence of symptoms are lacking, Dr. Riekert and colleagues noted in their abstract.
 

Sleep Quality, Anxiety, and Other Assessments

The researchers recruited a total of 236 AwCF aged 18 years and older from two cystic fibrosis (CF) centers between April 2021 and August 2022. They examined the prevalence of poor sleep quality, fatigue pain, depression, and anxiety in AwCF on the basis of five assessments: At baseline and at 3, 6, 9, and 12 months.

Participants were assessed via an online survey using the Fatigue Severity Scale (cutoff, > 4), Pittsburgh Sleep Quality Index (cutoff, > 5), Patient Health Questionnaire (cutoff, > 9), Generalized Anxiety Disorder (cutoff, > 9), and PROMIS Pain Intensity (cutoff, > 50 T score). Chronic symptoms were defined as positive scores on four or more assessments for individuals who completed four or five time-point assessments. The mean age of the participants was 37 years, 52% were women, 95% were non-Hispanic White, and 86% had been prescribed CF modulator therapy.

At 12 months, 62% of participants reported poor sleep, and 34% reported fatigue. In addition, 17% reported depressive symptoms, 14% reported anxiety symptoms, and 7% reported pain at 12 months.

Overall, 49% of participants met the criteria for chronic poor sleep quality, and 29% met the criteria for chronic fatigue, with positive assessments at four or more time points over the course of a year. In addition, 40%, 30%, and 18% of participants reported taking medication in the past 7 days for pain, mental health, and sleep, respectively.

The findings suggest that patients with CF might benefit from routine assessments of non-pulmonary symptoms in clinical care and from access to health care providers, including mental health professionals, to address non-pulmonary concerns, the researchers wrote in their abstract.

“We delayed starting the study until elexacaftor/tezacaftor/ivacaftor (ETI) was FDA-approved because there was an assumption that people with CF would have less fatigue because of respiratory improvements from ETI,” Dr. Riekert told this news organization. “Instead, the prevalence of fatigue and poor sleep quality was higher and more chronic than we had anticipated,” she noted.

However, “we were pleasantly surprised that depression and anxiety, while still prevalent, were less prevalent and chronic than previously reported,” Dr. Riekert said in an interview. “We attribute this to the CF Foundation’s mental health initiative that has increased the frequency of annual screening for depression and anxiety and provided resources to help people with cystic fibrosis obtain mental health services,” she said.

The study findings suggest that clinicians should assess people with CF for chronic fatigue and poor sleep along with depression and anxiety and provide treatment or referral, Dr. Riekert said. “For example, cognitive behavioral therapy can effectively treat all the symptoms that were measured in our study,” she noted.

Limitations of the study include the lack of data on how the non-respiratory symptoms interact with respiratory symptoms or pulmonary exacerbations, said Dr. Riekert. “While we assessed these symptoms five times, it was for a year; longer-term follow-up seems merited given our findings,” she said. In addition, “we need to study approaches to make cognitive behavioral therapy and other therapy more accessible for people with cystic fibrosis,” Dr. Riekert said.
 

Targeting Non-Pulmonary Dimensions of CF Care

The current study highlights an aspect of quality of life that is often forgotten when managing adults with CF and may affect their well-being despite effective therapy to improve function and prolong life, said Wissam Chatila, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

The high incidence of poor sleep, fatigue, depression, and anxiety seen in the current study was “somewhat surprising,” Dr. Chatila said. Also somewhat surprising was the chronicity of the symptoms considering the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (designed to correct the malfunctioning protein made by the CFTR gene) that have changed the face of CF, he noted.

However, recent growth in the number of adult patients with CF (more than 50% in certain countries) has led to a change in pathologies that physicians have to manage, and the current study addresses some of the emerging pathologies, said Dr. Chatila.

“Beyond demonstrating survival data from registries and other epidemiologic studies, this study sheds light on the need to address patient-reported outcomes that may or may not be directly related to the pulmonary and GI effects of the CFTR modulators,” he said. “Recognizing the extent of the dysfunction that many CF patients continue to suffer from will eventually lead to identifying factors that contribute to poor outcomes and the mechanisms involved,” he added.

Overall, the current study illustrates the potential benefits of offering personalized medicine to adults with CF that improves not only their physical function but also their mental health, Dr. Chatila said.

The study was funded by the Cystic Fibrosis Foundation. Dr. Riekert had no financial conflicts to disclose. Dr. Chatila had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Non-respiratory symptoms including poor sleep, fatigue, pain, anxiety, and depressive symptoms were prevalent among adults with cystic fibrosis (AwCF) and persisted after 1 year of follow-up, based on data from more than 200 individuals in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

“People with cystic fibrosis have qualitatively reported burden from extrapulmonary symptoms that were not being addressed by their health care providers; this is the first study to examine these symptoms concurrently in a large sample over time,” said lead author Kristin A. Riekert, PhD, of Johns Hopkins University, Baltimore, in an interview.

Previous cross-sectional studies have shown a high prevalence of poor sleep quality, fatigue, pain, depression, and anxiety among AwCF, but longitudinal data showing the persistence of symptoms are lacking, Dr. Riekert and colleagues noted in their abstract.
 

Sleep Quality, Anxiety, and Other Assessments

The researchers recruited a total of 236 AwCF aged 18 years and older from two cystic fibrosis (CF) centers between April 2021 and August 2022. They examined the prevalence of poor sleep quality, fatigue pain, depression, and anxiety in AwCF on the basis of five assessments: At baseline and at 3, 6, 9, and 12 months.

Participants were assessed via an online survey using the Fatigue Severity Scale (cutoff, > 4), Pittsburgh Sleep Quality Index (cutoff, > 5), Patient Health Questionnaire (cutoff, > 9), Generalized Anxiety Disorder (cutoff, > 9), and PROMIS Pain Intensity (cutoff, > 50 T score). Chronic symptoms were defined as positive scores on four or more assessments for individuals who completed four or five time-point assessments. The mean age of the participants was 37 years, 52% were women, 95% were non-Hispanic White, and 86% had been prescribed CF modulator therapy.

At 12 months, 62% of participants reported poor sleep, and 34% reported fatigue. In addition, 17% reported depressive symptoms, 14% reported anxiety symptoms, and 7% reported pain at 12 months.

Overall, 49% of participants met the criteria for chronic poor sleep quality, and 29% met the criteria for chronic fatigue, with positive assessments at four or more time points over the course of a year. In addition, 40%, 30%, and 18% of participants reported taking medication in the past 7 days for pain, mental health, and sleep, respectively.

The findings suggest that patients with CF might benefit from routine assessments of non-pulmonary symptoms in clinical care and from access to health care providers, including mental health professionals, to address non-pulmonary concerns, the researchers wrote in their abstract.

“We delayed starting the study until elexacaftor/tezacaftor/ivacaftor (ETI) was FDA-approved because there was an assumption that people with CF would have less fatigue because of respiratory improvements from ETI,” Dr. Riekert told this news organization. “Instead, the prevalence of fatigue and poor sleep quality was higher and more chronic than we had anticipated,” she noted.

However, “we were pleasantly surprised that depression and anxiety, while still prevalent, were less prevalent and chronic than previously reported,” Dr. Riekert said in an interview. “We attribute this to the CF Foundation’s mental health initiative that has increased the frequency of annual screening for depression and anxiety and provided resources to help people with cystic fibrosis obtain mental health services,” she said.

The study findings suggest that clinicians should assess people with CF for chronic fatigue and poor sleep along with depression and anxiety and provide treatment or referral, Dr. Riekert said. “For example, cognitive behavioral therapy can effectively treat all the symptoms that were measured in our study,” she noted.

Limitations of the study include the lack of data on how the non-respiratory symptoms interact with respiratory symptoms or pulmonary exacerbations, said Dr. Riekert. “While we assessed these symptoms five times, it was for a year; longer-term follow-up seems merited given our findings,” she said. In addition, “we need to study approaches to make cognitive behavioral therapy and other therapy more accessible for people with cystic fibrosis,” Dr. Riekert said.
 

Targeting Non-Pulmonary Dimensions of CF Care

The current study highlights an aspect of quality of life that is often forgotten when managing adults with CF and may affect their well-being despite effective therapy to improve function and prolong life, said Wissam Chatila, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

The high incidence of poor sleep, fatigue, depression, and anxiety seen in the current study was “somewhat surprising,” Dr. Chatila said. Also somewhat surprising was the chronicity of the symptoms considering the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (designed to correct the malfunctioning protein made by the CFTR gene) that have changed the face of CF, he noted.

However, recent growth in the number of adult patients with CF (more than 50% in certain countries) has led to a change in pathologies that physicians have to manage, and the current study addresses some of the emerging pathologies, said Dr. Chatila.

“Beyond demonstrating survival data from registries and other epidemiologic studies, this study sheds light on the need to address patient-reported outcomes that may or may not be directly related to the pulmonary and GI effects of the CFTR modulators,” he said. “Recognizing the extent of the dysfunction that many CF patients continue to suffer from will eventually lead to identifying factors that contribute to poor outcomes and the mechanisms involved,” he added.

Overall, the current study illustrates the potential benefits of offering personalized medicine to adults with CF that improves not only their physical function but also their mental health, Dr. Chatila said.

The study was funded by the Cystic Fibrosis Foundation. Dr. Riekert had no financial conflicts to disclose. Dr. Chatila had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

CHICAGO — Genetics and diet have been among the top theories for what may be fueling the troubling rise of colorectal cancer in young adults. Now, an early look at genetic data from people with colorectal cancer further suggests that the cause is linked to what is happening in the gut.

The findings were presented at the annual meeting of the American Society for Clinical Oncology (ASCO) by researchers from Ohio State University. For the analysis, they analyzed genetic data on tumors.

The researchers found signs that a high-fat, low-fiber diet may increase inflammation in the gut that prevents it from naturally suppressing tumors. The cells of young people with colorectal cancer also appeared to have aged more quickly — by 15 years on average — than a person’s actual age. That’s unusual, because older people with colorectal cancer don’t have the same boost in cellular aging.

The rate of colorectal cancer among young people has been rising at an alarming rate, according to a 2023 report from the American Cancer Society. In 2019, one in five colorectal cancer cases were among people younger than 55. That’s up from 1 in 10 in 1995, which means the rate has doubled in less than 30 years.
 

Need Colon Cancer Screening?

Who needs a colorectal cancer screening? Ask colorectal cancer specialist Nancy Kemeny, MD.

A 2017 analysis estimated that a person’s risk of colorectal cancer increased 12% by eating 3.5 ounces of red or processed meat daily, which is the equivalent of the size of a deck of playing cards. The same study also linked colorectal cancer risk to alcohol intake, citing its ethanol content. Eating a diet high in fiber can reduce a person’s risk.

This latest study aligned with previous findings that link bacteria called Fusobacterium to colorectal cancer. It’s not unusual for Fusobacterium to be present in a person’s mouth, but it is more likely to be found in the intestines of colorectal cancer patients, compared with those of healthy people. One study even found that people with colorectal cancer were five times more likely to have Fusobacterium in their stool, compared with healthy people.

Colorectal cancer is more common among men than women, “likely reflecting differences in risk factor prevalence, such as excess body weight and processed meat consumption,” the authors of the 2023 American Cancer Society report explained.

People younger than 45 should alert their medical provider if they have constipation, rectal bleeding, or sudden changes in bowel movements, which can be symptoms of colorectal cancer. Screening for colorectal cancer should begin for most people at age 45.

A version of this article appeared on WebMD.com.

CHICAGO — Genetics and diet have been among the top theories for what may be fueling the troubling rise of colorectal cancer in young adults. Now, an early look at genetic data from people with colorectal cancer further suggests that the cause is linked to what is happening in the gut.

The findings were presented at the annual meeting of the American Society for Clinical Oncology (ASCO) by researchers from Ohio State University. For the analysis, they analyzed genetic data on tumors.

The researchers found signs that a high-fat, low-fiber diet may increase inflammation in the gut that prevents it from naturally suppressing tumors. The cells of young people with colorectal cancer also appeared to have aged more quickly — by 15 years on average — than a person’s actual age. That’s unusual, because older people with colorectal cancer don’t have the same boost in cellular aging.

The rate of colorectal cancer among young people has been rising at an alarming rate, according to a 2023 report from the American Cancer Society. In 2019, one in five colorectal cancer cases were among people younger than 55. That’s up from 1 in 10 in 1995, which means the rate has doubled in less than 30 years.
 

Need Colon Cancer Screening?

Who needs a colorectal cancer screening? Ask colorectal cancer specialist Nancy Kemeny, MD.

A 2017 analysis estimated that a person’s risk of colorectal cancer increased 12% by eating 3.5 ounces of red or processed meat daily, which is the equivalent of the size of a deck of playing cards. The same study also linked colorectal cancer risk to alcohol intake, citing its ethanol content. Eating a diet high in fiber can reduce a person’s risk.

This latest study aligned with previous findings that link bacteria called Fusobacterium to colorectal cancer. It’s not unusual for Fusobacterium to be present in a person’s mouth, but it is more likely to be found in the intestines of colorectal cancer patients, compared with those of healthy people. One study even found that people with colorectal cancer were five times more likely to have Fusobacterium in their stool, compared with healthy people.

Colorectal cancer is more common among men than women, “likely reflecting differences in risk factor prevalence, such as excess body weight and processed meat consumption,” the authors of the 2023 American Cancer Society report explained.

People younger than 45 should alert their medical provider if they have constipation, rectal bleeding, or sudden changes in bowel movements, which can be symptoms of colorectal cancer. Screening for colorectal cancer should begin for most people at age 45.

A version of this article appeared on WebMD.com.

CHICAGO — Genetics and diet have been among the top theories for what may be fueling the troubling rise of colorectal cancer in young adults. Now, an early look at genetic data from people with colorectal cancer further suggests that the cause is linked to what is happening in the gut.

The findings were presented at the annual meeting of the American Society for Clinical Oncology (ASCO) by researchers from Ohio State University. For the analysis, they analyzed genetic data on tumors.

The researchers found signs that a high-fat, low-fiber diet may increase inflammation in the gut that prevents it from naturally suppressing tumors. The cells of young people with colorectal cancer also appeared to have aged more quickly — by 15 years on average — than a person’s actual age. That’s unusual, because older people with colorectal cancer don’t have the same boost in cellular aging.

The rate of colorectal cancer among young people has been rising at an alarming rate, according to a 2023 report from the American Cancer Society. In 2019, one in five colorectal cancer cases were among people younger than 55. That’s up from 1 in 10 in 1995, which means the rate has doubled in less than 30 years.
 

Need Colon Cancer Screening?

Who needs a colorectal cancer screening? Ask colorectal cancer specialist Nancy Kemeny, MD.

A 2017 analysis estimated that a person’s risk of colorectal cancer increased 12% by eating 3.5 ounces of red or processed meat daily, which is the equivalent of the size of a deck of playing cards. The same study also linked colorectal cancer risk to alcohol intake, citing its ethanol content. Eating a diet high in fiber can reduce a person’s risk.

This latest study aligned with previous findings that link bacteria called Fusobacterium to colorectal cancer. It’s not unusual for Fusobacterium to be present in a person’s mouth, but it is more likely to be found in the intestines of colorectal cancer patients, compared with those of healthy people. One study even found that people with colorectal cancer were five times more likely to have Fusobacterium in their stool, compared with healthy people.

Colorectal cancer is more common among men than women, “likely reflecting differences in risk factor prevalence, such as excess body weight and processed meat consumption,” the authors of the 2023 American Cancer Society report explained.

People younger than 45 should alert their medical provider if they have constipation, rectal bleeding, or sudden changes in bowel movements, which can be symptoms of colorectal cancer. Screening for colorectal cancer should begin for most people at age 45.

A version of this article appeared on WebMD.com.

The incidence of antidepressant discontinuation symptoms appears to be much lower than was previously thought, results from a new meta-analysis of studies assessing this issue showed.

After accounting for placebo effects, results showed that about 15% of patients who discontinue antidepressant therapy had true discontinuation symptoms, with severe symptoms occurring in about 2% of patients. 

“Considering all available data, we conservatively estimate that one out of every six to seven patients has truly pharmacologically-caused antidepressant discontinuation symptoms. This might still be an over-estimate, as it is difficult to factor in residual or re-emerging symptoms of depression or anxiety,” the researchers concluded. 

The study was published online in The Lancet.
 

More Reliable Data

“We are not saying all antidepressant discontinuation symptoms are a placebo effect. It is a real phenomenon. And we are not saying that there is no problem discontinuing antidepressants. But these findings suggest that true antidepressant discontinuation symptoms are lower than previous studies have suggested,” study investigator, Christopher Baethge, MD, University of Cologne, Germany, said at a Science Media Centre press briefing.

“Our data should de-emotionalize the debate on this issue. Yes, antidepressant discontinuation symptoms are a problem, but they should not cause undue alarm to patients or doctors,” Dr. Baethge added. 

Lead investigator, Jonathan Henssler, MD, Charité – Universitätsmedizin Berlin, Germany, noted that “previous studies on this issue have included surveys which have selection bias in that people with symptoms antidepressant discontinuation are more likely to participate. This study includes a broader range of research and excluded surveys, so we believe these are more reliable results.” 
 

A Controversial Issue

The investigators note that antidepressant discontinuation symptoms can be highly variable and nonspecific, with the most frequently reported symptoms being dizziness, headache, nausea, insomnia, and irritability. These symptoms typically occur within a few days and are usually transient but can last up to several weeks or months.

Explaining the mechanism behind the phenomenon, Dr. Baethge noted that selective serotonin reuptake inhibitor antidepressants increase the available serotonin in the brain, but the body responds by reducing the number of serotonin receptors. If the amount of available serotonin is reduced after stopping the medication, then this can lead to discontinuation symptoms. 

However, the incidence and severity of these symptoms remains controversial, the researchers noted. They point out that some estimates suggest that antidepressant discontinuation symptoms occurred in the majority of patients (56%), with almost half of cases classed as severe. 

Previous attempts at assessment have been questioned on methodologic grounds especially because of inclusion of online surveys or other studies prone to selection and dissatisfaction bias.

“Medical professionals continue to hold polarized positions on the incidence and severity of antidepressant discontinuation symptoms, and the debate continues in public media,” they wrote.

This is the first publication of a larger project on antidepressant discontinuation symptoms.

For the study, the researchers conducted a meta-analysis of 44 controlled trials and 35 observational studies assessing the incidence of antidepressant discontinuation symptoms including a total of 21,002 patients. Of these, 16,532 patients discontinued antidepressant treatment, and 4470 patients discontinued placebo. 

Incidence of at least one antidepressant discontinuation symptom occurred in 31% of patients stopping antidepressant therapy and in 17% after discontinuation of placebo, giving a true rate of pharmacologic-driven antidepressant discontinuation symptoms of 14%-15%.

The study also showed that severe discontinuation symptoms occurred in 2.8% of those stopping antidepressants and in 0.6% of those stopping placebo, giving a true rate of severe antidepressant discontinuation symptoms of around 2%. 

There was no association with treatment duration or with pharmaceutical company funding, and different statistical analyses produced similar results, suggesting the findings are robust, Dr. Baethge reported.

 

Risks by Medication

Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequency of discontinuation symptoms and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms.

Fluoxetine, sertraline, and citalopram had lower rates of discontinuation symptoms. No data were available for bupropion, mirtazapine, and amitriptyline.

As for the clinical implications of the findings, Dr. Henssler said that he does consider discontinuation symptoms when selecting a medication. “I would choose a drug with lower rate of these symptoms unless there was a specific reason to choose one with a higher rate,” he said. 

Dr. Henssler added that these data raise awareness of the placebo effect.

“Considering the placebo results, approximately half of antidepressant discontinuation symptoms could be attributable to expectation or non-specific symptoms,” the researchers noted.

“This is not to say all antidepressant discontinuation symptoms are caused by patient expectations; in practice, all patients discontinuing antidepressants need to be counseled and monitored, and patients who report antidepressant discontinuation symptoms must be helped, in particular those who develop severe antidepressant discontinuation symptoms,” they concluded.

 

Experts Weigh In

Commenting on the study at a press briefing, Oliver Howes, MD, chair of the psychopharmacology committee at the Royal College of Psychiatrists, United Kingdom, said that he welcomed “the insight that this robust study provides.”

“If someone chooses to stop taking their antidepressants, their doctor should help them to do so slowly and in a controlled manner that limits the impact of any potential withdrawal symptoms,” Dr. Howes said.

He added that the Royal College of Psychiatrists has produced a resource for patients and carers on stopping antidepressants that offers information on tapering medication at a pace that suits individual patient needs.

Also commenting, Tony Kendrick, MD, professor of primary care, University of Southampton, United Kingdom, pointed out some limitations of the new meta-analysis — in particular, that the method of assessment of discontinuation symptoms in the included studies was very variable, with specific measurement scales of discontinuation symptoms used in only six of the studies. 

“In most cases the assessment seemed to depend at least partly on the judgment of the authors of the included studies rather than being based on a systematic collection of data,” Dr. Kendrick added.

In an accompanying editorial, Glyn Lewis, PhD, and Gemma Lewis, PhD, University College London, United Kingdom, wrote that though the meta-analysis has its limitations, including the fact that many of the studies were small, often use antidepressants that are not commonly used now, and studied people who had not taken the antidepressants for a very long time, “the results here are a substantial improvement on anything that has been published before.”

They emphasize the importance of discussing the issue of a placebo effect with patients when stopping antidepressants. 

The editorialists pointed out that as antidepressants are prescribed to many millions of people, the relatively uncommon severe withdrawal symptoms will still affect a substantial number of people. However, for individual clinicians, severe withdrawal symptoms will seem uncommon, and most patients will probably not be troubled by antidepressant withdrawal, especially when medication is tapered over a few weeks.

They noted that cessation of antidepressants can lead to an increase in depressive and anxious symptoms, and distinguishing between relapsing symptoms and withdrawal is difficult. 

“Short-term symptoms that reduce quickly, without intervention, are best thought of as a form of withdrawal, even if those symptoms might be similar or identical to the symptoms of depression and anxiety. More serious and longer-term symptoms might best be managed by tapering more slowly, or even deciding to remain on the antidepressant,” the editorialists wrote.

There was no funding source for this study. The authors declare no competing interests. Dr. Kendrick led the NIHR REDUCE trial of internet and telephone support for antidepressant discontinuation and was a member of the guideline committee for the NICE 2022 Depression Guideline.

A version of this article appeared on Medscape.com.

The incidence of antidepressant discontinuation symptoms appears to be much lower than was previously thought, results from a new meta-analysis of studies assessing this issue showed.

After accounting for placebo effects, results showed that about 15% of patients who discontinue antidepressant therapy had true discontinuation symptoms, with severe symptoms occurring in about 2% of patients. 

“Considering all available data, we conservatively estimate that one out of every six to seven patients has truly pharmacologically-caused antidepressant discontinuation symptoms. This might still be an over-estimate, as it is difficult to factor in residual or re-emerging symptoms of depression or anxiety,” the researchers concluded. 

The study was published online in The Lancet.
 

More Reliable Data

“We are not saying all antidepressant discontinuation symptoms are a placebo effect. It is a real phenomenon. And we are not saying that there is no problem discontinuing antidepressants. But these findings suggest that true antidepressant discontinuation symptoms are lower than previous studies have suggested,” study investigator, Christopher Baethge, MD, University of Cologne, Germany, said at a Science Media Centre press briefing.

“Our data should de-emotionalize the debate on this issue. Yes, antidepressant discontinuation symptoms are a problem, but they should not cause undue alarm to patients or doctors,” Dr. Baethge added. 

Lead investigator, Jonathan Henssler, MD, Charité – Universitätsmedizin Berlin, Germany, noted that “previous studies on this issue have included surveys which have selection bias in that people with symptoms antidepressant discontinuation are more likely to participate. This study includes a broader range of research and excluded surveys, so we believe these are more reliable results.” 
 

A Controversial Issue

The investigators note that antidepressant discontinuation symptoms can be highly variable and nonspecific, with the most frequently reported symptoms being dizziness, headache, nausea, insomnia, and irritability. These symptoms typically occur within a few days and are usually transient but can last up to several weeks or months.

Explaining the mechanism behind the phenomenon, Dr. Baethge noted that selective serotonin reuptake inhibitor antidepressants increase the available serotonin in the brain, but the body responds by reducing the number of serotonin receptors. If the amount of available serotonin is reduced after stopping the medication, then this can lead to discontinuation symptoms. 

However, the incidence and severity of these symptoms remains controversial, the researchers noted. They point out that some estimates suggest that antidepressant discontinuation symptoms occurred in the majority of patients (56%), with almost half of cases classed as severe. 

Previous attempts at assessment have been questioned on methodologic grounds especially because of inclusion of online surveys or other studies prone to selection and dissatisfaction bias.

“Medical professionals continue to hold polarized positions on the incidence and severity of antidepressant discontinuation symptoms, and the debate continues in public media,” they wrote.

This is the first publication of a larger project on antidepressant discontinuation symptoms.

For the study, the researchers conducted a meta-analysis of 44 controlled trials and 35 observational studies assessing the incidence of antidepressant discontinuation symptoms including a total of 21,002 patients. Of these, 16,532 patients discontinued antidepressant treatment, and 4470 patients discontinued placebo. 

Incidence of at least one antidepressant discontinuation symptom occurred in 31% of patients stopping antidepressant therapy and in 17% after discontinuation of placebo, giving a true rate of pharmacologic-driven antidepressant discontinuation symptoms of 14%-15%.

The study also showed that severe discontinuation symptoms occurred in 2.8% of those stopping antidepressants and in 0.6% of those stopping placebo, giving a true rate of severe antidepressant discontinuation symptoms of around 2%. 

There was no association with treatment duration or with pharmaceutical company funding, and different statistical analyses produced similar results, suggesting the findings are robust, Dr. Baethge reported.

 

Risks by Medication

Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequency of discontinuation symptoms and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms.

Fluoxetine, sertraline, and citalopram had lower rates of discontinuation symptoms. No data were available for bupropion, mirtazapine, and amitriptyline.

As for the clinical implications of the findings, Dr. Henssler said that he does consider discontinuation symptoms when selecting a medication. “I would choose a drug with lower rate of these symptoms unless there was a specific reason to choose one with a higher rate,” he said. 

Dr. Henssler added that these data raise awareness of the placebo effect.

“Considering the placebo results, approximately half of antidepressant discontinuation symptoms could be attributable to expectation or non-specific symptoms,” the researchers noted.

“This is not to say all antidepressant discontinuation symptoms are caused by patient expectations; in practice, all patients discontinuing antidepressants need to be counseled and monitored, and patients who report antidepressant discontinuation symptoms must be helped, in particular those who develop severe antidepressant discontinuation symptoms,” they concluded.

 

Experts Weigh In

Commenting on the study at a press briefing, Oliver Howes, MD, chair of the psychopharmacology committee at the Royal College of Psychiatrists, United Kingdom, said that he welcomed “the insight that this robust study provides.”

“If someone chooses to stop taking their antidepressants, their doctor should help them to do so slowly and in a controlled manner that limits the impact of any potential withdrawal symptoms,” Dr. Howes said.

He added that the Royal College of Psychiatrists has produced a resource for patients and carers on stopping antidepressants that offers information on tapering medication at a pace that suits individual patient needs.

Also commenting, Tony Kendrick, MD, professor of primary care, University of Southampton, United Kingdom, pointed out some limitations of the new meta-analysis — in particular, that the method of assessment of discontinuation symptoms in the included studies was very variable, with specific measurement scales of discontinuation symptoms used in only six of the studies. 

“In most cases the assessment seemed to depend at least partly on the judgment of the authors of the included studies rather than being based on a systematic collection of data,” Dr. Kendrick added.

In an accompanying editorial, Glyn Lewis, PhD, and Gemma Lewis, PhD, University College London, United Kingdom, wrote that though the meta-analysis has its limitations, including the fact that many of the studies were small, often use antidepressants that are not commonly used now, and studied people who had not taken the antidepressants for a very long time, “the results here are a substantial improvement on anything that has been published before.”

They emphasize the importance of discussing the issue of a placebo effect with patients when stopping antidepressants. 

The editorialists pointed out that as antidepressants are prescribed to many millions of people, the relatively uncommon severe withdrawal symptoms will still affect a substantial number of people. However, for individual clinicians, severe withdrawal symptoms will seem uncommon, and most patients will probably not be troubled by antidepressant withdrawal, especially when medication is tapered over a few weeks.

They noted that cessation of antidepressants can lead to an increase in depressive and anxious symptoms, and distinguishing between relapsing symptoms and withdrawal is difficult. 

“Short-term symptoms that reduce quickly, without intervention, are best thought of as a form of withdrawal, even if those symptoms might be similar or identical to the symptoms of depression and anxiety. More serious and longer-term symptoms might best be managed by tapering more slowly, or even deciding to remain on the antidepressant,” the editorialists wrote.

There was no funding source for this study. The authors declare no competing interests. Dr. Kendrick led the NIHR REDUCE trial of internet and telephone support for antidepressant discontinuation and was a member of the guideline committee for the NICE 2022 Depression Guideline.

A version of this article appeared on Medscape.com.

The incidence of antidepressant discontinuation symptoms appears to be much lower than was previously thought, results from a new meta-analysis of studies assessing this issue showed.

After accounting for placebo effects, results showed that about 15% of patients who discontinue antidepressant therapy had true discontinuation symptoms, with severe symptoms occurring in about 2% of patients. 

“Considering all available data, we conservatively estimate that one out of every six to seven patients has truly pharmacologically-caused antidepressant discontinuation symptoms. This might still be an over-estimate, as it is difficult to factor in residual or re-emerging symptoms of depression or anxiety,” the researchers concluded. 

The study was published online in The Lancet.
 

More Reliable Data

“We are not saying all antidepressant discontinuation symptoms are a placebo effect. It is a real phenomenon. And we are not saying that there is no problem discontinuing antidepressants. But these findings suggest that true antidepressant discontinuation symptoms are lower than previous studies have suggested,” study investigator, Christopher Baethge, MD, University of Cologne, Germany, said at a Science Media Centre press briefing.

“Our data should de-emotionalize the debate on this issue. Yes, antidepressant discontinuation symptoms are a problem, but they should not cause undue alarm to patients or doctors,” Dr. Baethge added. 

Lead investigator, Jonathan Henssler, MD, Charité – Universitätsmedizin Berlin, Germany, noted that “previous studies on this issue have included surveys which have selection bias in that people with symptoms antidepressant discontinuation are more likely to participate. This study includes a broader range of research and excluded surveys, so we believe these are more reliable results.” 
 

A Controversial Issue

The investigators note that antidepressant discontinuation symptoms can be highly variable and nonspecific, with the most frequently reported symptoms being dizziness, headache, nausea, insomnia, and irritability. These symptoms typically occur within a few days and are usually transient but can last up to several weeks or months.

Explaining the mechanism behind the phenomenon, Dr. Baethge noted that selective serotonin reuptake inhibitor antidepressants increase the available serotonin in the brain, but the body responds by reducing the number of serotonin receptors. If the amount of available serotonin is reduced after stopping the medication, then this can lead to discontinuation symptoms. 

However, the incidence and severity of these symptoms remains controversial, the researchers noted. They point out that some estimates suggest that antidepressant discontinuation symptoms occurred in the majority of patients (56%), with almost half of cases classed as severe. 

Previous attempts at assessment have been questioned on methodologic grounds especially because of inclusion of online surveys or other studies prone to selection and dissatisfaction bias.

“Medical professionals continue to hold polarized positions on the incidence and severity of antidepressant discontinuation symptoms, and the debate continues in public media,” they wrote.

This is the first publication of a larger project on antidepressant discontinuation symptoms.

For the study, the researchers conducted a meta-analysis of 44 controlled trials and 35 observational studies assessing the incidence of antidepressant discontinuation symptoms including a total of 21,002 patients. Of these, 16,532 patients discontinued antidepressant treatment, and 4470 patients discontinued placebo. 

Incidence of at least one antidepressant discontinuation symptom occurred in 31% of patients stopping antidepressant therapy and in 17% after discontinuation of placebo, giving a true rate of pharmacologic-driven antidepressant discontinuation symptoms of 14%-15%.

The study also showed that severe discontinuation symptoms occurred in 2.8% of those stopping antidepressants and in 0.6% of those stopping placebo, giving a true rate of severe antidepressant discontinuation symptoms of around 2%. 

There was no association with treatment duration or with pharmaceutical company funding, and different statistical analyses produced similar results, suggesting the findings are robust, Dr. Baethge reported.

 

Risks by Medication

Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequency of discontinuation symptoms and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms.

Fluoxetine, sertraline, and citalopram had lower rates of discontinuation symptoms. No data were available for bupropion, mirtazapine, and amitriptyline.

As for the clinical implications of the findings, Dr. Henssler said that he does consider discontinuation symptoms when selecting a medication. “I would choose a drug with lower rate of these symptoms unless there was a specific reason to choose one with a higher rate,” he said. 

Dr. Henssler added that these data raise awareness of the placebo effect.

“Considering the placebo results, approximately half of antidepressant discontinuation symptoms could be attributable to expectation or non-specific symptoms,” the researchers noted.

“This is not to say all antidepressant discontinuation symptoms are caused by patient expectations; in practice, all patients discontinuing antidepressants need to be counseled and monitored, and patients who report antidepressant discontinuation symptoms must be helped, in particular those who develop severe antidepressant discontinuation symptoms,” they concluded.

 

Experts Weigh In

Commenting on the study at a press briefing, Oliver Howes, MD, chair of the psychopharmacology committee at the Royal College of Psychiatrists, United Kingdom, said that he welcomed “the insight that this robust study provides.”

“If someone chooses to stop taking their antidepressants, their doctor should help them to do so slowly and in a controlled manner that limits the impact of any potential withdrawal symptoms,” Dr. Howes said.

He added that the Royal College of Psychiatrists has produced a resource for patients and carers on stopping antidepressants that offers information on tapering medication at a pace that suits individual patient needs.

Also commenting, Tony Kendrick, MD, professor of primary care, University of Southampton, United Kingdom, pointed out some limitations of the new meta-analysis — in particular, that the method of assessment of discontinuation symptoms in the included studies was very variable, with specific measurement scales of discontinuation symptoms used in only six of the studies. 

“In most cases the assessment seemed to depend at least partly on the judgment of the authors of the included studies rather than being based on a systematic collection of data,” Dr. Kendrick added.

In an accompanying editorial, Glyn Lewis, PhD, and Gemma Lewis, PhD, University College London, United Kingdom, wrote that though the meta-analysis has its limitations, including the fact that many of the studies were small, often use antidepressants that are not commonly used now, and studied people who had not taken the antidepressants for a very long time, “the results here are a substantial improvement on anything that has been published before.”

They emphasize the importance of discussing the issue of a placebo effect with patients when stopping antidepressants. 

The editorialists pointed out that as antidepressants are prescribed to many millions of people, the relatively uncommon severe withdrawal symptoms will still affect a substantial number of people. However, for individual clinicians, severe withdrawal symptoms will seem uncommon, and most patients will probably not be troubled by antidepressant withdrawal, especially when medication is tapered over a few weeks.

They noted that cessation of antidepressants can lead to an increase in depressive and anxious symptoms, and distinguishing between relapsing symptoms and withdrawal is difficult. 

“Short-term symptoms that reduce quickly, without intervention, are best thought of as a form of withdrawal, even if those symptoms might be similar or identical to the symptoms of depression and anxiety. More serious and longer-term symptoms might best be managed by tapering more slowly, or even deciding to remain on the antidepressant,” the editorialists wrote.

There was no funding source for this study. The authors declare no competing interests. Dr. Kendrick led the NIHR REDUCE trial of internet and telephone support for antidepressant discontinuation and was a member of the guideline committee for the NICE 2022 Depression Guideline.

A version of this article appeared on Medscape.com.