AVAHO

Chimeric antigen receptor (CAR) T-cell therapy is generally associated with good long-term neuropsychiatric status, based on a recent patient-reported outcomes study.

But almost one out of five patients may have notably worse cognitive and psychiatric outcomes within 1-5 years of therapy, reported Julia Ruark, MD, of the University of Washington, Seattle, and colleagues. According to Dr. Ruark and associates, this latter finding suggests that CAR T-cell therapy may negatively impact mental health in a subset of patients.

These findings provide clinical insight into a minimally researched patient population.

“At this time, only limited data are available regarding the long-term effects of CAR T-cell therapy,” the investigators wrote in Biology of Blood and Marrow Transplantation. “Thus, it is important to evaluate the late neuropsychiatric effects of CAR T and evaluate their effect on survivors’ quality of life.”

The study involved 40 patients with relapsed or refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia. Before undergoing CAR T-cell therapy, patients underwent standardized mental health screening with validated instruments such as the 7-item Generalized Anxiety Disorder scale. At least 1 year after CAR T-cell therapy, patients completed a questionnaire consisting of the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 Global Health and the PROMIS-29 Profile v2.1, and 30 additional questions, 4 of which evaluated cognitive function. These data were converted to T scores for comparative purposes.

Patients who underwent CAR T-cell therapy had statistically similar T scores to the general population mean, suggesting comparable overall neuropsychiatric status. However, a closer look at the data showed that almost one out of five patients who underwent CAR T-cell therapy had global mental health scores that were at least 1 standard deviation lower than the mean for the general population and patients with cancer.

Almost half of the patients (47.5%) who underwent CAR T-cell therapy reported at least one clinically meaningful negative neuropsychiatric outcome. Specifically, 20% reported cognitive difficulties and depression or anxiety, 17.5% reported cognitive difficulties without depression or anxiety, and 10% reported depression or anxiety without cognitive difficulties. One-quarter (25%) of patients reported taking a medication for depression, 20% reported use of anxiolytics, and 15% reported use of sleep medications. Multivariate analysis revealed an association between younger age and depression (P = .01), anxiety (P = .001), and worse long-term global mental health (P = .02). Cognitive difficulties were significantly more common among patients with worse physical and/or mental health.

“[A] subset of patients may experience psychiatric symptoms or cognitive impairment [which may be related to CAR T-cell therapy or other treatments patients have been exposed to], and it is important to identify those patients to assist with intervention strategies,” the investigators concluded.The study was funded by the National Institutes of Health, Life Science Discovery Fund, Juno Therapeutics/Celgene, and others. The investigators reported additional relationships with Nektar Therapeutics, Allogene Therapeutics, T-CURX, and others.

SOURCE: Ruark J et al. Biol Blood Marrow Transplant. 2019 Oct 9. doi: 10.1016/j.bbmt.2019.09.037.

Chimeric antigen receptor (CAR) T-cell therapy is generally associated with good long-term neuropsychiatric status, based on a recent patient-reported outcomes study.

But almost one out of five patients may have notably worse cognitive and psychiatric outcomes within 1-5 years of therapy, reported Julia Ruark, MD, of the University of Washington, Seattle, and colleagues. According to Dr. Ruark and associates, this latter finding suggests that CAR T-cell therapy may negatively impact mental health in a subset of patients.

These findings provide clinical insight into a minimally researched patient population.

“At this time, only limited data are available regarding the long-term effects of CAR T-cell therapy,” the investigators wrote in Biology of Blood and Marrow Transplantation. “Thus, it is important to evaluate the late neuropsychiatric effects of CAR T and evaluate their effect on survivors’ quality of life.”

The study involved 40 patients with relapsed or refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia. Before undergoing CAR T-cell therapy, patients underwent standardized mental health screening with validated instruments such as the 7-item Generalized Anxiety Disorder scale. At least 1 year after CAR T-cell therapy, patients completed a questionnaire consisting of the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 Global Health and the PROMIS-29 Profile v2.1, and 30 additional questions, 4 of which evaluated cognitive function. These data were converted to T scores for comparative purposes.

Patients who underwent CAR T-cell therapy had statistically similar T scores to the general population mean, suggesting comparable overall neuropsychiatric status. However, a closer look at the data showed that almost one out of five patients who underwent CAR T-cell therapy had global mental health scores that were at least 1 standard deviation lower than the mean for the general population and patients with cancer.

Almost half of the patients (47.5%) who underwent CAR T-cell therapy reported at least one clinically meaningful negative neuropsychiatric outcome. Specifically, 20% reported cognitive difficulties and depression or anxiety, 17.5% reported cognitive difficulties without depression or anxiety, and 10% reported depression or anxiety without cognitive difficulties. One-quarter (25%) of patients reported taking a medication for depression, 20% reported use of anxiolytics, and 15% reported use of sleep medications. Multivariate analysis revealed an association between younger age and depression (P = .01), anxiety (P = .001), and worse long-term global mental health (P = .02). Cognitive difficulties were significantly more common among patients with worse physical and/or mental health.

“[A] subset of patients may experience psychiatric symptoms or cognitive impairment [which may be related to CAR T-cell therapy or other treatments patients have been exposed to], and it is important to identify those patients to assist with intervention strategies,” the investigators concluded.The study was funded by the National Institutes of Health, Life Science Discovery Fund, Juno Therapeutics/Celgene, and others. The investigators reported additional relationships with Nektar Therapeutics, Allogene Therapeutics, T-CURX, and others.

SOURCE: Ruark J et al. Biol Blood Marrow Transplant. 2019 Oct 9. doi: 10.1016/j.bbmt.2019.09.037.

Chimeric antigen receptor (CAR) T-cell therapy is generally associated with good long-term neuropsychiatric status, based on a recent patient-reported outcomes study.

But almost one out of five patients may have notably worse cognitive and psychiatric outcomes within 1-5 years of therapy, reported Julia Ruark, MD, of the University of Washington, Seattle, and colleagues. According to Dr. Ruark and associates, this latter finding suggests that CAR T-cell therapy may negatively impact mental health in a subset of patients.

These findings provide clinical insight into a minimally researched patient population.

“At this time, only limited data are available regarding the long-term effects of CAR T-cell therapy,” the investigators wrote in Biology of Blood and Marrow Transplantation. “Thus, it is important to evaluate the late neuropsychiatric effects of CAR T and evaluate their effect on survivors’ quality of life.”

The study involved 40 patients with relapsed or refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia. Before undergoing CAR T-cell therapy, patients underwent standardized mental health screening with validated instruments such as the 7-item Generalized Anxiety Disorder scale. At least 1 year after CAR T-cell therapy, patients completed a questionnaire consisting of the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 Global Health and the PROMIS-29 Profile v2.1, and 30 additional questions, 4 of which evaluated cognitive function. These data were converted to T scores for comparative purposes.

Patients who underwent CAR T-cell therapy had statistically similar T scores to the general population mean, suggesting comparable overall neuropsychiatric status. However, a closer look at the data showed that almost one out of five patients who underwent CAR T-cell therapy had global mental health scores that were at least 1 standard deviation lower than the mean for the general population and patients with cancer.

Almost half of the patients (47.5%) who underwent CAR T-cell therapy reported at least one clinically meaningful negative neuropsychiatric outcome. Specifically, 20% reported cognitive difficulties and depression or anxiety, 17.5% reported cognitive difficulties without depression or anxiety, and 10% reported depression or anxiety without cognitive difficulties. One-quarter (25%) of patients reported taking a medication for depression, 20% reported use of anxiolytics, and 15% reported use of sleep medications. Multivariate analysis revealed an association between younger age and depression (P = .01), anxiety (P = .001), and worse long-term global mental health (P = .02). Cognitive difficulties were significantly more common among patients with worse physical and/or mental health.

“[A] subset of patients may experience psychiatric symptoms or cognitive impairment [which may be related to CAR T-cell therapy or other treatments patients have been exposed to], and it is important to identify those patients to assist with intervention strategies,” the investigators concluded.The study was funded by the National Institutes of Health, Life Science Discovery Fund, Juno Therapeutics/Celgene, and others. The investigators reported additional relationships with Nektar Therapeutics, Allogene Therapeutics, T-CURX, and others.

SOURCE: Ruark J et al. Biol Blood Marrow Transplant. 2019 Oct 9. doi: 10.1016/j.bbmt.2019.09.037.

Declines in death rates for lung cancer and melanoma have gained momentum in recent years, fueling a record drop in cancer mortality, the American Cancer Society says.

Lung cancer death rates, which were falling by 3% in men and 2% in women annually in 2008 through 2013, dropped by 5% in men and nearly 4% per year in women annually from 2013 to 2017, according to the society’s 2020 statistical report.

Those accelerating reductions in death rates helped fuel the biggest-ever single year decline in overall cancer mortality, of 2.2%, from 2016 to 2017, their report shows.

According to the investigators, the decline in melanoma death rates escalated to 6.9% per year among 20- to 49-year-olds over 2013-2017, compared with a decline of just 2.9% per year during 2006-2010. Likewise, the melanoma death rate decline was 7.2% annually for the more recent time period, compared with just 1.3% annually in the earlier time period. The finding was even more remarkable for those 65 years of age and older, according to investigators, since the declines in melanoma death rates reached 6.2% annually, compared with a 0.9% annual increase in the years before immunotherapy.

Smoking cessation has been the main driver of progress in cutting lung cancer death rates, according to the report, while in melanoma, death rates have dropped after the introduction of immune checkpoint inhibitors and targeted therapies.

By contrast, reductions in death rates have slowed for colorectal cancers and female breast cancers, and have stabilized for prostate cancer, Ms. Siegel and coauthors stated, adding that racial and geographic disparities persist in preventable cancers, including those of the lung and cervix.

“Increased investment in both the equitable application of existing cancer control interventions and basic and clinical research to further advance treatment options would undoubtedly accelerate progress against cancer,” said the investigators. The report appears in CA: A Cancer Journal for Clinicians.

While the decline in lung cancer death rates is good news, the disease remains a major killer, responsible for more deaths than breast, colorectal, and ovarian cancer combined, said Jacques P. Fontaine, MD, a thoracic surgeon at Moffitt Cancer Center in Tampa, Fla.

“Five-year survival rates are still around the 18%-20% range, which is much lower than breast and prostate cancer,” Dr. Fontaine said in an interview. “Nonetheless, we’ve made a little dent in that, and we’re improving.”

Two other factors that have helped spur that improvement, according to Dr. Fontaine, are the reduced incidence of squamous cell carcinomas, which are linked to smoking, and the increased use of lung cancer screening with low-dose computed tomography.

Squamous cell carcinomas tend to be a central rather than peripheral, which makes the tumors harder to resect: “Surgery is sometimes not an option, and even to this day in 2020, the single most effective treatment for lung cancer remains surgical resection,” said Dr. Fontaine.

Likewise, centrally located tumors may preclude giving high-dose radiation and may result in more “collateral damage” to healthy tissue, he added.

Landmark studies show that low-dose CT scans reduce lung cancer deaths by 20% or more; however, screening can have false-positive results that lead to unnecessary biopsies and other harms, suggesting that the procedures should be done in centers of excellence that provide high-quality, responsible screening for early lung cancer, Dr. Fontaine said.

While the drop in melanoma death rates is encouraging and, not surprising in light of new cutting-edge therapies, an ongoing unmet treatment need still exists, according to Vishal Anil Patel, MD, director of cutaneous oncology at the George Washington Cancer Center in Washington.

“We still have a lot to learn, and a way to go, because we’ve really just made the first breakthrough,” Dr. Patel said in an interview.

SOURCE: Siegel RL et al. CA Cancer J Clin. 2020;70(1):7-30. doi: 10.3322/caac.21590.

Declines in death rates for lung cancer and melanoma have gained momentum in recent years, fueling a record drop in cancer mortality, the American Cancer Society says.

Lung cancer death rates, which were falling by 3% in men and 2% in women annually in 2008 through 2013, dropped by 5% in men and nearly 4% per year in women annually from 2013 to 2017, according to the society’s 2020 statistical report.

Those accelerating reductions in death rates helped fuel the biggest-ever single year decline in overall cancer mortality, of 2.2%, from 2016 to 2017, their report shows.

According to the investigators, the decline in melanoma death rates escalated to 6.9% per year among 20- to 49-year-olds over 2013-2017, compared with a decline of just 2.9% per year during 2006-2010. Likewise, the melanoma death rate decline was 7.2% annually for the more recent time period, compared with just 1.3% annually in the earlier time period. The finding was even more remarkable for those 65 years of age and older, according to investigators, since the declines in melanoma death rates reached 6.2% annually, compared with a 0.9% annual increase in the years before immunotherapy.

Smoking cessation has been the main driver of progress in cutting lung cancer death rates, according to the report, while in melanoma, death rates have dropped after the introduction of immune checkpoint inhibitors and targeted therapies.

By contrast, reductions in death rates have slowed for colorectal cancers and female breast cancers, and have stabilized for prostate cancer, Ms. Siegel and coauthors stated, adding that racial and geographic disparities persist in preventable cancers, including those of the lung and cervix.

“Increased investment in both the equitable application of existing cancer control interventions and basic and clinical research to further advance treatment options would undoubtedly accelerate progress against cancer,” said the investigators. The report appears in CA: A Cancer Journal for Clinicians.

While the decline in lung cancer death rates is good news, the disease remains a major killer, responsible for more deaths than breast, colorectal, and ovarian cancer combined, said Jacques P. Fontaine, MD, a thoracic surgeon at Moffitt Cancer Center in Tampa, Fla.

“Five-year survival rates are still around the 18%-20% range, which is much lower than breast and prostate cancer,” Dr. Fontaine said in an interview. “Nonetheless, we’ve made a little dent in that, and we’re improving.”

Two other factors that have helped spur that improvement, according to Dr. Fontaine, are the reduced incidence of squamous cell carcinomas, which are linked to smoking, and the increased use of lung cancer screening with low-dose computed tomography.

Squamous cell carcinomas tend to be a central rather than peripheral, which makes the tumors harder to resect: “Surgery is sometimes not an option, and even to this day in 2020, the single most effective treatment for lung cancer remains surgical resection,” said Dr. Fontaine.

Likewise, centrally located tumors may preclude giving high-dose radiation and may result in more “collateral damage” to healthy tissue, he added.

Landmark studies show that low-dose CT scans reduce lung cancer deaths by 20% or more; however, screening can have false-positive results that lead to unnecessary biopsies and other harms, suggesting that the procedures should be done in centers of excellence that provide high-quality, responsible screening for early lung cancer, Dr. Fontaine said.

While the drop in melanoma death rates is encouraging and, not surprising in light of new cutting-edge therapies, an ongoing unmet treatment need still exists, according to Vishal Anil Patel, MD, director of cutaneous oncology at the George Washington Cancer Center in Washington.

“We still have a lot to learn, and a way to go, because we’ve really just made the first breakthrough,” Dr. Patel said in an interview.

SOURCE: Siegel RL et al. CA Cancer J Clin. 2020;70(1):7-30. doi: 10.3322/caac.21590.

Declines in death rates for lung cancer and melanoma have gained momentum in recent years, fueling a record drop in cancer mortality, the American Cancer Society says.

Lung cancer death rates, which were falling by 3% in men and 2% in women annually in 2008 through 2013, dropped by 5% in men and nearly 4% per year in women annually from 2013 to 2017, according to the society’s 2020 statistical report.

Those accelerating reductions in death rates helped fuel the biggest-ever single year decline in overall cancer mortality, of 2.2%, from 2016 to 2017, their report shows.

According to the investigators, the decline in melanoma death rates escalated to 6.9% per year among 20- to 49-year-olds over 2013-2017, compared with a decline of just 2.9% per year during 2006-2010. Likewise, the melanoma death rate decline was 7.2% annually for the more recent time period, compared with just 1.3% annually in the earlier time period. The finding was even more remarkable for those 65 years of age and older, according to investigators, since the declines in melanoma death rates reached 6.2% annually, compared with a 0.9% annual increase in the years before immunotherapy.

Smoking cessation has been the main driver of progress in cutting lung cancer death rates, according to the report, while in melanoma, death rates have dropped after the introduction of immune checkpoint inhibitors and targeted therapies.

By contrast, reductions in death rates have slowed for colorectal cancers and female breast cancers, and have stabilized for prostate cancer, Ms. Siegel and coauthors stated, adding that racial and geographic disparities persist in preventable cancers, including those of the lung and cervix.

“Increased investment in both the equitable application of existing cancer control interventions and basic and clinical research to further advance treatment options would undoubtedly accelerate progress against cancer,” said the investigators. The report appears in CA: A Cancer Journal for Clinicians.

While the decline in lung cancer death rates is good news, the disease remains a major killer, responsible for more deaths than breast, colorectal, and ovarian cancer combined, said Jacques P. Fontaine, MD, a thoracic surgeon at Moffitt Cancer Center in Tampa, Fla.

“Five-year survival rates are still around the 18%-20% range, which is much lower than breast and prostate cancer,” Dr. Fontaine said in an interview. “Nonetheless, we’ve made a little dent in that, and we’re improving.”

Two other factors that have helped spur that improvement, according to Dr. Fontaine, are the reduced incidence of squamous cell carcinomas, which are linked to smoking, and the increased use of lung cancer screening with low-dose computed tomography.

Squamous cell carcinomas tend to be a central rather than peripheral, which makes the tumors harder to resect: “Surgery is sometimes not an option, and even to this day in 2020, the single most effective treatment for lung cancer remains surgical resection,” said Dr. Fontaine.

Likewise, centrally located tumors may preclude giving high-dose radiation and may result in more “collateral damage” to healthy tissue, he added.

Landmark studies show that low-dose CT scans reduce lung cancer deaths by 20% or more; however, screening can have false-positive results that lead to unnecessary biopsies and other harms, suggesting that the procedures should be done in centers of excellence that provide high-quality, responsible screening for early lung cancer, Dr. Fontaine said.

While the drop in melanoma death rates is encouraging and, not surprising in light of new cutting-edge therapies, an ongoing unmet treatment need still exists, according to Vishal Anil Patel, MD, director of cutaneous oncology at the George Washington Cancer Center in Washington.

“We still have a lot to learn, and a way to go, because we’ve really just made the first breakthrough,” Dr. Patel said in an interview.

SOURCE: Siegel RL et al. CA Cancer J Clin. 2020;70(1):7-30. doi: 10.3322/caac.21590.

PHILADELPHIA – Testosterone gel for treatment of hypogonadism in older men boosted their left ventricular mass by 3.5% in a single year in the multicenter, double-blind, placebo-controlled Testosterone Cardiovascular Trial, although the clinical implications of this impressive increase remain unclear, Elizabeth Hutchins, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

“I do think these results should be considered as part of the safety profile for testosterone gel and also represent an interesting and understudied area for future research,” said Dr. Hutchins, a hospitalist affiliated with the Los Angeles Biomedical Research Center at Harbor-UCLA Medical Center.

The Testosterone Cardiovascular Trial was one of seven coordinated placebo-controlled, double-blind clinical trials of the impact of raising serum testosterone levels in older men with low testosterone. Some results of what are known as the TTrials have previously been reported (Endocr Rev. 2018 Jun 1;39[3]:369-86).

Dr. Hutchins presented new findings on the effect of treatment with 1% topical testosterone gel on body surface area–indexed left ventricular mass. The trial utilized a widely prescribed, commercially available product known as AndroGel. The study included 123 men over age 65 with low serum testosterone and coronary CT angiography images obtained at baseline and again after 1 year of double-blind testosterone gel or placebo. More than 80% of the men were above age 75, half were obese, more than two-thirds had hypertension, and 30% had diabetes.

The men initially applied 5 g of the testosterone gel daily, providing 15 mg/day of testosterone, with subsequent dosing adjustments as needed based on serum testosterone levels measured at a central laboratory. Participants were evaluated in office visits with serum testosterone measurements every 3 months. Testosterone levels in the men assigned to active treatment quickly rose to normal range and stayed there for the full 12 months, while the placebo-treated controls continued to have below-normal testosterone throughout the trial.

The key study finding was that LV mass indexed to body surface area rose significantly in the testosterone gel group, from an average of 71.5 g/m² at baseline to 74.8 g/m² at 1 year. That’s a statistically significant 3.5% increase. In contrast, LV mass remained flat across the year in controls: 73.8 g/m² at baseline and 73.3 g/m² at 12 months.

There was, however, no change over time in left or right atrial or ventricular chamber volumes in the testosterone gel recipients, nor in the controls.

Session comoderator Eric D. Peterson, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C., said that “this is a very important topic,” then posed a provocative question to Dr. Hutchins: “If the intervention had been running instead of testosterone gel, would the results have looked similar, and would you be concluding that there should be a warning around the use of running?”

Dr. Hutchins replied that she’s given that question much thought.

“Of course, exercise leads to LV hypertrophy and we consider that to be good muscle, and high blood pressure leads to LV hypertrophy and we consider that bad muscle. So which one is it in this case? From what I can find in the literature, it seems that incremental increases in LV mass in the absence of being an athlete are deleterious. But I think we would need outcomes-based research to really answer that question,” she said.

Dr. Hutchins noted that this was the first-ever randomized controlled trial to measure the effect of testosterone therapy on LV mass in humans. The documented increase achieved with 1 year of testosterone gel doesn’t come close to reaching the threshold of LV hypertrophy, which is about 125 g/m² for men. But evidence from animal and observational human studies suggests that even in the absence of LV hypertrophy, increases in LV mass are associated with increased mortality, she added.

She reported having no financial conflicts regarding her study, sponsored by the National Institutes of Health.

[email protected]

SOURCE: Hutchins E. AHA 2019, Session FS.AOS.04.

PHILADELPHIA – Testosterone gel for treatment of hypogonadism in older men boosted their left ventricular mass by 3.5% in a single year in the multicenter, double-blind, placebo-controlled Testosterone Cardiovascular Trial, although the clinical implications of this impressive increase remain unclear, Elizabeth Hutchins, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

“I do think these results should be considered as part of the safety profile for testosterone gel and also represent an interesting and understudied area for future research,” said Dr. Hutchins, a hospitalist affiliated with the Los Angeles Biomedical Research Center at Harbor-UCLA Medical Center.

The Testosterone Cardiovascular Trial was one of seven coordinated placebo-controlled, double-blind clinical trials of the impact of raising serum testosterone levels in older men with low testosterone. Some results of what are known as the TTrials have previously been reported (Endocr Rev. 2018 Jun 1;39[3]:369-86).

Dr. Hutchins presented new findings on the effect of treatment with 1% topical testosterone gel on body surface area–indexed left ventricular mass. The trial utilized a widely prescribed, commercially available product known as AndroGel. The study included 123 men over age 65 with low serum testosterone and coronary CT angiography images obtained at baseline and again after 1 year of double-blind testosterone gel or placebo. More than 80% of the men were above age 75, half were obese, more than two-thirds had hypertension, and 30% had diabetes.

The men initially applied 5 g of the testosterone gel daily, providing 15 mg/day of testosterone, with subsequent dosing adjustments as needed based on serum testosterone levels measured at a central laboratory. Participants were evaluated in office visits with serum testosterone measurements every 3 months. Testosterone levels in the men assigned to active treatment quickly rose to normal range and stayed there for the full 12 months, while the placebo-treated controls continued to have below-normal testosterone throughout the trial.

The key study finding was that LV mass indexed to body surface area rose significantly in the testosterone gel group, from an average of 71.5 g/m² at baseline to 74.8 g/m² at 1 year. That’s a statistically significant 3.5% increase. In contrast, LV mass remained flat across the year in controls: 73.8 g/m² at baseline and 73.3 g/m² at 12 months.

There was, however, no change over time in left or right atrial or ventricular chamber volumes in the testosterone gel recipients, nor in the controls.

Session comoderator Eric D. Peterson, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C., said that “this is a very important topic,” then posed a provocative question to Dr. Hutchins: “If the intervention had been running instead of testosterone gel, would the results have looked similar, and would you be concluding that there should be a warning around the use of running?”

Dr. Hutchins replied that she’s given that question much thought.

“Of course, exercise leads to LV hypertrophy and we consider that to be good muscle, and high blood pressure leads to LV hypertrophy and we consider that bad muscle. So which one is it in this case? From what I can find in the literature, it seems that incremental increases in LV mass in the absence of being an athlete are deleterious. But I think we would need outcomes-based research to really answer that question,” she said.

Dr. Hutchins noted that this was the first-ever randomized controlled trial to measure the effect of testosterone therapy on LV mass in humans. The documented increase achieved with 1 year of testosterone gel doesn’t come close to reaching the threshold of LV hypertrophy, which is about 125 g/m² for men. But evidence from animal and observational human studies suggests that even in the absence of LV hypertrophy, increases in LV mass are associated with increased mortality, she added.

She reported having no financial conflicts regarding her study, sponsored by the National Institutes of Health.

[email protected]

SOURCE: Hutchins E. AHA 2019, Session FS.AOS.04.

PHILADELPHIA – Testosterone gel for treatment of hypogonadism in older men boosted their left ventricular mass by 3.5% in a single year in the multicenter, double-blind, placebo-controlled Testosterone Cardiovascular Trial, although the clinical implications of this impressive increase remain unclear, Elizabeth Hutchins, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

“I do think these results should be considered as part of the safety profile for testosterone gel and also represent an interesting and understudied area for future research,” said Dr. Hutchins, a hospitalist affiliated with the Los Angeles Biomedical Research Center at Harbor-UCLA Medical Center.

The Testosterone Cardiovascular Trial was one of seven coordinated placebo-controlled, double-blind clinical trials of the impact of raising serum testosterone levels in older men with low testosterone. Some results of what are known as the TTrials have previously been reported (Endocr Rev. 2018 Jun 1;39[3]:369-86).

Dr. Hutchins presented new findings on the effect of treatment with 1% topical testosterone gel on body surface area–indexed left ventricular mass. The trial utilized a widely prescribed, commercially available product known as AndroGel. The study included 123 men over age 65 with low serum testosterone and coronary CT angiography images obtained at baseline and again after 1 year of double-blind testosterone gel or placebo. More than 80% of the men were above age 75, half were obese, more than two-thirds had hypertension, and 30% had diabetes.

The men initially applied 5 g of the testosterone gel daily, providing 15 mg/day of testosterone, with subsequent dosing adjustments as needed based on serum testosterone levels measured at a central laboratory. Participants were evaluated in office visits with serum testosterone measurements every 3 months. Testosterone levels in the men assigned to active treatment quickly rose to normal range and stayed there for the full 12 months, while the placebo-treated controls continued to have below-normal testosterone throughout the trial.

The key study finding was that LV mass indexed to body surface area rose significantly in the testosterone gel group, from an average of 71.5 g/m² at baseline to 74.8 g/m² at 1 year. That’s a statistically significant 3.5% increase. In contrast, LV mass remained flat across the year in controls: 73.8 g/m² at baseline and 73.3 g/m² at 12 months.

There was, however, no change over time in left or right atrial or ventricular chamber volumes in the testosterone gel recipients, nor in the controls.

Session comoderator Eric D. Peterson, MD, professor of medicine and a cardiologist at Duke University in Durham, N.C., said that “this is a very important topic,” then posed a provocative question to Dr. Hutchins: “If the intervention had been running instead of testosterone gel, would the results have looked similar, and would you be concluding that there should be a warning around the use of running?”

Dr. Hutchins replied that she’s given that question much thought.

“Of course, exercise leads to LV hypertrophy and we consider that to be good muscle, and high blood pressure leads to LV hypertrophy and we consider that bad muscle. So which one is it in this case? From what I can find in the literature, it seems that incremental increases in LV mass in the absence of being an athlete are deleterious. But I think we would need outcomes-based research to really answer that question,” she said.

Dr. Hutchins noted that this was the first-ever randomized controlled trial to measure the effect of testosterone therapy on LV mass in humans. The documented increase achieved with 1 year of testosterone gel doesn’t come close to reaching the threshold of LV hypertrophy, which is about 125 g/m² for men. But evidence from animal and observational human studies suggests that even in the absence of LV hypertrophy, increases in LV mass are associated with increased mortality, she added.

She reported having no financial conflicts regarding her study, sponsored by the National Institutes of Health.

[email protected]

SOURCE: Hutchins E. AHA 2019, Session FS.AOS.04.

The Food and Drug Administration has issued a Safety Alert regarding the weight-management medication lorcaserin (Belviq, Belviq XR) after results from a clinical trial assessing the drug’s safety showed a possible increased risk of cancer.

bankrx/Getty Images

“At this time, the cause of the cancer is uncertain, and we cannot conclude that lorcaserin contributes to the cancer risk. However, we wanted to make the public aware of this potential risk,” the agency said in a press release.

The agency advised that health care providers consider whether the benefits of taking lorcaserin outweighed the potential cancer risk, and that patients currently taking the medication should talk to their providers about the risks.

“We are continuing to evaluate the clinical trial results and will communicate our final conclusions and recommendations when we have completed our review,” the FDA noted in the statement.

Lorcaserin, a serotonin 2C receptor agonist, was approved by the FDA in 2012 at a dosage of 20 mg once daily for use with a reduced-calorie diet and increased physical activity as a means to improve weight loss in adults who are obese or overweight and have at least one weight-related medical problem, such as such as hypertension, type 2 diabetes, or dyslipidemia. In July 2016, the agency approved a New Drug Application for an extended-release, once-daily formulation.

Headache, dizziness, fatigue, nausea, dry mouth, and constipation are the more common adverse effects in patients without diabetes, whereas hypoglycemia, headache, back pain, cough, and fatigue are more common in patients with diabetes. The treatment is contraindicated for pregnancy.

Lorcaserin is distributed by Eisai.*

[email protected]

*Correction, 1/15/2020: An earlier version of this story misstated the manufacturer of lorcaserin. 

The Food and Drug Administration has issued a Safety Alert regarding the weight-management medication lorcaserin (Belviq, Belviq XR) after results from a clinical trial assessing the drug’s safety showed a possible increased risk of cancer.

bankrx/Getty Images

“At this time, the cause of the cancer is uncertain, and we cannot conclude that lorcaserin contributes to the cancer risk. However, we wanted to make the public aware of this potential risk,” the agency said in a press release.

The agency advised that health care providers consider whether the benefits of taking lorcaserin outweighed the potential cancer risk, and that patients currently taking the medication should talk to their providers about the risks.

“We are continuing to evaluate the clinical trial results and will communicate our final conclusions and recommendations when we have completed our review,” the FDA noted in the statement.

Lorcaserin, a serotonin 2C receptor agonist, was approved by the FDA in 2012 at a dosage of 20 mg once daily for use with a reduced-calorie diet and increased physical activity as a means to improve weight loss in adults who are obese or overweight and have at least one weight-related medical problem, such as such as hypertension, type 2 diabetes, or dyslipidemia. In July 2016, the agency approved a New Drug Application for an extended-release, once-daily formulation.

Headache, dizziness, fatigue, nausea, dry mouth, and constipation are the more common adverse effects in patients without diabetes, whereas hypoglycemia, headache, back pain, cough, and fatigue are more common in patients with diabetes. The treatment is contraindicated for pregnancy.

Lorcaserin is distributed by Eisai.*

[email protected]

*Correction, 1/15/2020: An earlier version of this story misstated the manufacturer of lorcaserin. 

The Food and Drug Administration has issued a Safety Alert regarding the weight-management medication lorcaserin (Belviq, Belviq XR) after results from a clinical trial assessing the drug’s safety showed a possible increased risk of cancer.

bankrx/Getty Images

“At this time, the cause of the cancer is uncertain, and we cannot conclude that lorcaserin contributes to the cancer risk. However, we wanted to make the public aware of this potential risk,” the agency said in a press release.

The agency advised that health care providers consider whether the benefits of taking lorcaserin outweighed the potential cancer risk, and that patients currently taking the medication should talk to their providers about the risks.

“We are continuing to evaluate the clinical trial results and will communicate our final conclusions and recommendations when we have completed our review,” the FDA noted in the statement.

Lorcaserin, a serotonin 2C receptor agonist, was approved by the FDA in 2012 at a dosage of 20 mg once daily for use with a reduced-calorie diet and increased physical activity as a means to improve weight loss in adults who are obese or overweight and have at least one weight-related medical problem, such as such as hypertension, type 2 diabetes, or dyslipidemia. In July 2016, the agency approved a New Drug Application for an extended-release, once-daily formulation.

Headache, dizziness, fatigue, nausea, dry mouth, and constipation are the more common adverse effects in patients without diabetes, whereas hypoglycemia, headache, back pain, cough, and fatigue are more common in patients with diabetes. The treatment is contraindicated for pregnancy.

Lorcaserin is distributed by Eisai.*

[email protected]

*Correction, 1/15/2020: An earlier version of this story misstated the manufacturer of lorcaserin. 

New data suggest an increased risk of leukemia among responders who worked at the World Trade Center site after the attacks on Sept. 11, 2001.

Courtesy Andrea Booher/FEMA News Photo

Previous studies have shown that 9/11 responders have a higher incidence of cancers than does the general population. The current study is the first to show a higher incidence of leukemia among responders. It also shows a higher incidence of thyroid and prostate cancers as well as all cancer types combined.

These findings were published in JNCI Cancer Spectrum.

“This study showed increased incidence of several cancer types compared to previously conducted studies with shorter follow-up periods,” study author Susan L, Teitelbaum, PhD, of the Icahn School of Medicine at Mount Sinai, New York, said in a press release.

“Because of the long latency period of many types of cancer, it is possible that increased rates of other cancers, as well as World Trade Center exposure health issues, may emerge after longer periods of study.”

Dr. Teitelbaum and colleagues evaluated responders enrolled in the World Trade Center Health Program General Responder Cohort from when it was established in July 2002 through the end of follow-up, which was Dec. 31, 2013, for New York residents and Dec. 31, 2012, for residents of other states.

To be eligible for the cohort, responders must have worked on the World Trade Center rescue and recovery effort a minimum of 4 hours in the first 4 days from Sept. 11, 2001, 24 hours in September 2001, or 80 hours from September through December 2001. Responders also had to complete at least one monitoring visit.

Responders’ data were linked to data from cancer registries in New York, New Jersey, Pennsylvania, and Connecticut (where most responders lived at the time of the attacks), as well as Florida and North Carolina (where responders were known to retire). The responders were linked to the registries using probabilistic matching algorithms, which made use of information such as patient name, address, social security number, sex, race, and birth date.

The researchers noted that patients who enrolled in the General Responder Cohort had their cancer certified for federally funded treatment, and this factor might result in “sicker members disproportionately self-selecting into the program.” To reduce this potential bias, the researchers conducted a restricted analysis in which counts of cancer cases and person-years of observation began 6 months after responder enrollment.

The researchers analyzed data on 28,729 responders who primarily worked in protective services (49.0%) and construction (20.8%). Responders spent a median of 52 days on the rescue and recovery effort, and 44.4% of them had some exposure to the dust cloud caused by the collapse of the towers.

In the restricted analysis, there were 1,072 cancers observed in 999 responders. Compared with the general population, responders had a significantly higher incidence of all cancers combined, with a standardized incidence ratio (SIR) of 1.09.

Responders had a significantly higher incidence of prostate cancer (SIR,1.25), thyroid cancer (SIR, 2.19), and leukemia (SIR, 1.41). The leukemia category included acute myeloid leukemia (SIR,1.58) and chronic lymphocytic leukemia (SIR, 1.08).

“Although other studies have revealed elevated SIRs for other hematologic malignancies, this is the first reported, statistically significant, elevated SIR for leukemia,” the researchers wrote. “Leukemia is known to occur after exposure to occupational carcinogens, including benzene (burning jet fuel and other sources at the [World Trade Center] site), possibly at low levels of exposure and with a latency of several years from exposure.”

A multivariate analysis showed no association between cancer incidence and the length of time responders spent on the rescue and recovery effort or the intensity of their exposure to the dust cloud or debris pile.

The analysis did show an elevated risk of all cancers combined with each 1-year increase in responder age (hazard ratio, 1.09), among male responders (HR, 1.21), and among responders who smoked at baseline (HR, 1.29).

This research was supported by the Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. The researchers disclosed no conflicts of interest.
 

[email protected]

SOURCE: Shapiro MZ et al. JNCI Cancer Spectr. 2020 Jan 14. doi: 10.1093/jncics/pkz090.

New data suggest an increased risk of leukemia among responders who worked at the World Trade Center site after the attacks on Sept. 11, 2001.

Courtesy Andrea Booher/FEMA News Photo

Previous studies have shown that 9/11 responders have a higher incidence of cancers than does the general population. The current study is the first to show a higher incidence of leukemia among responders. It also shows a higher incidence of thyroid and prostate cancers as well as all cancer types combined.

These findings were published in JNCI Cancer Spectrum.

“This study showed increased incidence of several cancer types compared to previously conducted studies with shorter follow-up periods,” study author Susan L, Teitelbaum, PhD, of the Icahn School of Medicine at Mount Sinai, New York, said in a press release.

“Because of the long latency period of many types of cancer, it is possible that increased rates of other cancers, as well as World Trade Center exposure health issues, may emerge after longer periods of study.”

Dr. Teitelbaum and colleagues evaluated responders enrolled in the World Trade Center Health Program General Responder Cohort from when it was established in July 2002 through the end of follow-up, which was Dec. 31, 2013, for New York residents and Dec. 31, 2012, for residents of other states.

To be eligible for the cohort, responders must have worked on the World Trade Center rescue and recovery effort a minimum of 4 hours in the first 4 days from Sept. 11, 2001, 24 hours in September 2001, or 80 hours from September through December 2001. Responders also had to complete at least one monitoring visit.

Responders’ data were linked to data from cancer registries in New York, New Jersey, Pennsylvania, and Connecticut (where most responders lived at the time of the attacks), as well as Florida and North Carolina (where responders were known to retire). The responders were linked to the registries using probabilistic matching algorithms, which made use of information such as patient name, address, social security number, sex, race, and birth date.

The researchers noted that patients who enrolled in the General Responder Cohort had their cancer certified for federally funded treatment, and this factor might result in “sicker members disproportionately self-selecting into the program.” To reduce this potential bias, the researchers conducted a restricted analysis in which counts of cancer cases and person-years of observation began 6 months after responder enrollment.

The researchers analyzed data on 28,729 responders who primarily worked in protective services (49.0%) and construction (20.8%). Responders spent a median of 52 days on the rescue and recovery effort, and 44.4% of them had some exposure to the dust cloud caused by the collapse of the towers.

In the restricted analysis, there were 1,072 cancers observed in 999 responders. Compared with the general population, responders had a significantly higher incidence of all cancers combined, with a standardized incidence ratio (SIR) of 1.09.

Responders had a significantly higher incidence of prostate cancer (SIR,1.25), thyroid cancer (SIR, 2.19), and leukemia (SIR, 1.41). The leukemia category included acute myeloid leukemia (SIR,1.58) and chronic lymphocytic leukemia (SIR, 1.08).

“Although other studies have revealed elevated SIRs for other hematologic malignancies, this is the first reported, statistically significant, elevated SIR for leukemia,” the researchers wrote. “Leukemia is known to occur after exposure to occupational carcinogens, including benzene (burning jet fuel and other sources at the [World Trade Center] site), possibly at low levels of exposure and with a latency of several years from exposure.”

A multivariate analysis showed no association between cancer incidence and the length of time responders spent on the rescue and recovery effort or the intensity of their exposure to the dust cloud or debris pile.

The analysis did show an elevated risk of all cancers combined with each 1-year increase in responder age (hazard ratio, 1.09), among male responders (HR, 1.21), and among responders who smoked at baseline (HR, 1.29).

This research was supported by the Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. The researchers disclosed no conflicts of interest.
 

[email protected]

SOURCE: Shapiro MZ et al. JNCI Cancer Spectr. 2020 Jan 14. doi: 10.1093/jncics/pkz090.

New data suggest an increased risk of leukemia among responders who worked at the World Trade Center site after the attacks on Sept. 11, 2001.

Courtesy Andrea Booher/FEMA News Photo

Previous studies have shown that 9/11 responders have a higher incidence of cancers than does the general population. The current study is the first to show a higher incidence of leukemia among responders. It also shows a higher incidence of thyroid and prostate cancers as well as all cancer types combined.

These findings were published in JNCI Cancer Spectrum.

“This study showed increased incidence of several cancer types compared to previously conducted studies with shorter follow-up periods,” study author Susan L, Teitelbaum, PhD, of the Icahn School of Medicine at Mount Sinai, New York, said in a press release.

“Because of the long latency period of many types of cancer, it is possible that increased rates of other cancers, as well as World Trade Center exposure health issues, may emerge after longer periods of study.”

Dr. Teitelbaum and colleagues evaluated responders enrolled in the World Trade Center Health Program General Responder Cohort from when it was established in July 2002 through the end of follow-up, which was Dec. 31, 2013, for New York residents and Dec. 31, 2012, for residents of other states.

To be eligible for the cohort, responders must have worked on the World Trade Center rescue and recovery effort a minimum of 4 hours in the first 4 days from Sept. 11, 2001, 24 hours in September 2001, or 80 hours from September through December 2001. Responders also had to complete at least one monitoring visit.

Responders’ data were linked to data from cancer registries in New York, New Jersey, Pennsylvania, and Connecticut (where most responders lived at the time of the attacks), as well as Florida and North Carolina (where responders were known to retire). The responders were linked to the registries using probabilistic matching algorithms, which made use of information such as patient name, address, social security number, sex, race, and birth date.

The researchers noted that patients who enrolled in the General Responder Cohort had their cancer certified for federally funded treatment, and this factor might result in “sicker members disproportionately self-selecting into the program.” To reduce this potential bias, the researchers conducted a restricted analysis in which counts of cancer cases and person-years of observation began 6 months after responder enrollment.

The researchers analyzed data on 28,729 responders who primarily worked in protective services (49.0%) and construction (20.8%). Responders spent a median of 52 days on the rescue and recovery effort, and 44.4% of them had some exposure to the dust cloud caused by the collapse of the towers.

In the restricted analysis, there were 1,072 cancers observed in 999 responders. Compared with the general population, responders had a significantly higher incidence of all cancers combined, with a standardized incidence ratio (SIR) of 1.09.

Responders had a significantly higher incidence of prostate cancer (SIR,1.25), thyroid cancer (SIR, 2.19), and leukemia (SIR, 1.41). The leukemia category included acute myeloid leukemia (SIR,1.58) and chronic lymphocytic leukemia (SIR, 1.08).

“Although other studies have revealed elevated SIRs for other hematologic malignancies, this is the first reported, statistically significant, elevated SIR for leukemia,” the researchers wrote. “Leukemia is known to occur after exposure to occupational carcinogens, including benzene (burning jet fuel and other sources at the [World Trade Center] site), possibly at low levels of exposure and with a latency of several years from exposure.”

A multivariate analysis showed no association between cancer incidence and the length of time responders spent on the rescue and recovery effort or the intensity of their exposure to the dust cloud or debris pile.

The analysis did show an elevated risk of all cancers combined with each 1-year increase in responder age (hazard ratio, 1.09), among male responders (HR, 1.21), and among responders who smoked at baseline (HR, 1.29).

This research was supported by the Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. The researchers disclosed no conflicts of interest.
 

[email protected]

SOURCE: Shapiro MZ et al. JNCI Cancer Spectr. 2020 Jan 14. doi: 10.1093/jncics/pkz090.

Eradication of Helicobacter pylori infection was associated with a more than 75% decrease in hazard of subsequent stomach cancer in a large retrospective cohort study.

Simply being treated for H. pylori infection did not mitigate the risk of gastric adenocarcinoma, and patients whose H. pylori was not eradicated were at increased risk, said Shria Kumar, MD, of the Perelman Center for Advanced Medicine in Philadelphia, and with her associates. “This speaks to the ability of H. pylori eradication to modify future risks of gastric adenocarcinoma, and the need to not only treat those diagnosed with H. pylori, but to confirm eradication, and re-treat those who fail eradication,” they wrote in Gastroenterology.

Gastric adenocarcinoma remains a grave diagnosis, with a 5-year survival rate of less than 30%. Although H. pylori infection is an established risk factor for gastric cancer (particularly nonproximal disease), most studies have used national cancer databases that do not track H. pylori infection. Accordingly, Dr. Kumar and her associates analyzed data for 371,813 patients diagnosed with H. pylori infection at U.S. Veterans Health Administration facilities between 1994 and 2018. A total of 92% of patients were men, 58% were white, 24% were black, and approximately 1% each were Native American, Asian, or Native Hawaiian/Pacific Islander. Median age was 62 years.

Patients with H. pylori infection who subsequently were diagnosed with nonproximal gastric cancer were significantly (P less than .001) more likely to be older (median age, 65.1 vs. 62.0 years), current or historical smokers, or racial or ethnic minorities (black or African American, Asian, or Hispanic/Latino), compared with patients with H. pylori who did not develop cancer. In the multivariable analysis, standardized hazard ratios for these variables remained statistically significant, with point estimates ranging from 1.13 (for each 5-year increase in age at diagnosis of infection) to 2.00 (for black or African American race). Cumulative incidence rates of distal gastric adenocarcinoma following H. pylori infection were 0.37% at 5 years, 0.5% at 10 years, and 0.65% at 20 year.

Patients whose infections were confirmed to have been eradicated were at markedly lower risk for subsequent gastric cancer than were patients whose infections were not eradicated (SHR, 0.24; 95% confidence interval, 0.15-0.41; P less than .001). Importantly, simply being treated for H. pylori did not significantly affect cancer risk (SHR, 1.16; 95% CI, 0.74-1.83).

Rates in Japan are approximately five times higher, while in sub-Saharan Africa, H. pylori infection is prevalent but gastric cancer is uncommon, the researchers noted. These discrepancies support the idea that carcinogenesis depends on additional genetic or environmental variables in addition to H. pylori infection alone, they said. They called for future studies of protective factors.

Dr. Kumar is supported by a training grant from the National Institutes of Health. She disclosed travel support from Boston Scientific and Olympus. Her coinvestigators disclosed ties to Takeda, Novartis, Janssen, Gilead, Bayer, and several other companies.

SOURCE: Kumar S et al. Gastroenterology. 2019 Jul 31. doi: 10.1053/j.gastro.2019.10.019.

Eradication of Helicobacter pylori infection was associated with a more than 75% decrease in hazard of subsequent stomach cancer in a large retrospective cohort study.

Simply being treated for H. pylori infection did not mitigate the risk of gastric adenocarcinoma, and patients whose H. pylori was not eradicated were at increased risk, said Shria Kumar, MD, of the Perelman Center for Advanced Medicine in Philadelphia, and with her associates. “This speaks to the ability of H. pylori eradication to modify future risks of gastric adenocarcinoma, and the need to not only treat those diagnosed with H. pylori, but to confirm eradication, and re-treat those who fail eradication,” they wrote in Gastroenterology.

Gastric adenocarcinoma remains a grave diagnosis, with a 5-year survival rate of less than 30%. Although H. pylori infection is an established risk factor for gastric cancer (particularly nonproximal disease), most studies have used national cancer databases that do not track H. pylori infection. Accordingly, Dr. Kumar and her associates analyzed data for 371,813 patients diagnosed with H. pylori infection at U.S. Veterans Health Administration facilities between 1994 and 2018. A total of 92% of patients were men, 58% were white, 24% were black, and approximately 1% each were Native American, Asian, or Native Hawaiian/Pacific Islander. Median age was 62 years.

Patients with H. pylori infection who subsequently were diagnosed with nonproximal gastric cancer were significantly (P less than .001) more likely to be older (median age, 65.1 vs. 62.0 years), current or historical smokers, or racial or ethnic minorities (black or African American, Asian, or Hispanic/Latino), compared with patients with H. pylori who did not develop cancer. In the multivariable analysis, standardized hazard ratios for these variables remained statistically significant, with point estimates ranging from 1.13 (for each 5-year increase in age at diagnosis of infection) to 2.00 (for black or African American race). Cumulative incidence rates of distal gastric adenocarcinoma following H. pylori infection were 0.37% at 5 years, 0.5% at 10 years, and 0.65% at 20 year.

Patients whose infections were confirmed to have been eradicated were at markedly lower risk for subsequent gastric cancer than were patients whose infections were not eradicated (SHR, 0.24; 95% confidence interval, 0.15-0.41; P less than .001). Importantly, simply being treated for H. pylori did not significantly affect cancer risk (SHR, 1.16; 95% CI, 0.74-1.83).

Rates in Japan are approximately five times higher, while in sub-Saharan Africa, H. pylori infection is prevalent but gastric cancer is uncommon, the researchers noted. These discrepancies support the idea that carcinogenesis depends on additional genetic or environmental variables in addition to H. pylori infection alone, they said. They called for future studies of protective factors.

Dr. Kumar is supported by a training grant from the National Institutes of Health. She disclosed travel support from Boston Scientific and Olympus. Her coinvestigators disclosed ties to Takeda, Novartis, Janssen, Gilead, Bayer, and several other companies.

SOURCE: Kumar S et al. Gastroenterology. 2019 Jul 31. doi: 10.1053/j.gastro.2019.10.019.

Eradication of Helicobacter pylori infection was associated with a more than 75% decrease in hazard of subsequent stomach cancer in a large retrospective cohort study.

Simply being treated for H. pylori infection did not mitigate the risk of gastric adenocarcinoma, and patients whose H. pylori was not eradicated were at increased risk, said Shria Kumar, MD, of the Perelman Center for Advanced Medicine in Philadelphia, and with her associates. “This speaks to the ability of H. pylori eradication to modify future risks of gastric adenocarcinoma, and the need to not only treat those diagnosed with H. pylori, but to confirm eradication, and re-treat those who fail eradication,” they wrote in Gastroenterology.

Gastric adenocarcinoma remains a grave diagnosis, with a 5-year survival rate of less than 30%. Although H. pylori infection is an established risk factor for gastric cancer (particularly nonproximal disease), most studies have used national cancer databases that do not track H. pylori infection. Accordingly, Dr. Kumar and her associates analyzed data for 371,813 patients diagnosed with H. pylori infection at U.S. Veterans Health Administration facilities between 1994 and 2018. A total of 92% of patients were men, 58% were white, 24% were black, and approximately 1% each were Native American, Asian, or Native Hawaiian/Pacific Islander. Median age was 62 years.

Patients with H. pylori infection who subsequently were diagnosed with nonproximal gastric cancer were significantly (P less than .001) more likely to be older (median age, 65.1 vs. 62.0 years), current or historical smokers, or racial or ethnic minorities (black or African American, Asian, or Hispanic/Latino), compared with patients with H. pylori who did not develop cancer. In the multivariable analysis, standardized hazard ratios for these variables remained statistically significant, with point estimates ranging from 1.13 (for each 5-year increase in age at diagnosis of infection) to 2.00 (for black or African American race). Cumulative incidence rates of distal gastric adenocarcinoma following H. pylori infection were 0.37% at 5 years, 0.5% at 10 years, and 0.65% at 20 year.

Patients whose infections were confirmed to have been eradicated were at markedly lower risk for subsequent gastric cancer than were patients whose infections were not eradicated (SHR, 0.24; 95% confidence interval, 0.15-0.41; P less than .001). Importantly, simply being treated for H. pylori did not significantly affect cancer risk (SHR, 1.16; 95% CI, 0.74-1.83).

Rates in Japan are approximately five times higher, while in sub-Saharan Africa, H. pylori infection is prevalent but gastric cancer is uncommon, the researchers noted. These discrepancies support the idea that carcinogenesis depends on additional genetic or environmental variables in addition to H. pylori infection alone, they said. They called for future studies of protective factors.

Dr. Kumar is supported by a training grant from the National Institutes of Health. She disclosed travel support from Boston Scientific and Olympus. Her coinvestigators disclosed ties to Takeda, Novartis, Janssen, Gilead, Bayer, and several other companies.

SOURCE: Kumar S et al. Gastroenterology. 2019 Jul 31. doi: 10.1053/j.gastro.2019.10.019.

Hepatocellular carcinoma (HCC) tissue contains several unique populations of tumor infiltrating cells, including some exhausted effector T cells that regain normal function when treated with the immunotherapy drug nivolumab, according to researchers.

The unique populations of recently activated CD4+, CD8+, and CD4-CD8 double-negative cells identified in the tumors expressed specific activation markers and inhibitor receptors, according to investigators, who have published the results of their immune profiling analyses in Cellular and Molecular Gastroenterology and Hepatology.

“Importantly, these cells expressed markers of activation and tissue residence, possibly suggesting activation within the tumor,” said Daniela Di Blasi, PhD, and the others researchers, of the University of Basel in Switzerland.

A further look at tumor histology revealed an accumulation of those activated T cells in immune-inflamed HCC, according to the investigators, who added that enumeration of specific tumor-infiltrating lymphocytes could represent “a prognostic indicator of therapy responsiveness.”

However, they advised caution in interpreting the results to date: “We are aware that the analysis described here is based on a small number of patients and that validation of its prognostic value requires ad hoc prospective studies that include more patients,” they said in their report.

The researcher’s findings were based on analysis of HCC biopsies before and after treatment with the immune checkpoint inhibitor nivolumab, nontumor liver tissue biopsies, and peripheral blood samples from 36 patients, most of whom were male, and about half of whom had cirrhosis. Investigators used multiparametric flow cytometry to characterize expression of activation markers including CD137, CD150, and ICOS, among others, as well as expression of inhibitory receptors including TIGIT and PD1.

Compared with nonneoplastic liver tissue, tumor tissue was enriched with T cells expressing the activation marker CD137 and the inhibitory receptor ICOS, indicating that HCC tumor-infiltrating lymphocytes “are different from liver-resident T cells and might have immunologic relevance,” Dr. Di Blasi and coauthors said in their report.

Further analysis revealed several cell populations unique to HCC samples, the authors said, including CD4+ T cells coexpressing ICOS and TIGIT, which tended to accumulate in tumor tissue, compared with nontumor tissue and peripheral blood mononuclear cells. Those CD4+ tumor-infiltrating T cells were functionally impaired, they added, as shown by a lack of cytokine production.

Activated CD8+ T cells likewise preferentially accumulated in tumor tissue, and most of those tumor-infiltrating cells expressed CD38 and PD1. The presence of these proliferating and functional cells may contribute to local inflammation and antitumor response, according to the investigators, who also identified two unique populations of double-negative T cells, including some that expressed CD137, which they said was a marker of recent T-cell activation.

The investigators also looked at the presence of tumor-infiltrating lymphocytes correlated to the presence of mononuclear cell infiltrate in tumor tissue. They found that immune-inflamed tumors had significantly increased proliferation of unique CD4+, CD8+, and double-negative T cell populations.

Nivolumab treatment appeared to substantially reduce the proportion of impaired CD4+ T cells, while increasing the percentage of interferon gamma–producing CD38+ CD4+ T cells and also promoting enrichment of interferon gamma–producing CD38+ CD8+ cells. Those increases in release of interferon gamma may have a positive influence on antitumor immunity via modulation of immune and tumor cell functions, according to the investigators.

Not all immune-inflamed tumors responded to nivolumab treatment, suggesting that an immune-inflamed profile is “necessary but not sufficient” for clinical response to an anti-PD1 agent, noted Dr. Di Blasi and colleagues.

Taken together, the researchers said their investigations suggest the presence of unique populations of T cells that might be providing effective anti-tumor immunity.

“These studies set the point for the identification of the tumor antigens stimulating these T cells and their possible exploitation as immunotherapeutic targets in HCC,” they concluded in the report.

The study was supported by grants from the European Research Council and the Swiss Initiative in Systems Biology, among others. Dr. Di Blasi and coauthors disclosed no conflicts of interest.

SOURCE: Di Blasi D et al. Cell Mol Gastroenterol Hepatol. 2019 Aug 22. doi: 10.1016/j.jcmgh.2019.08.004.

Hepatocellular carcinoma (HCC) tissue contains several unique populations of tumor infiltrating cells, including some exhausted effector T cells that regain normal function when treated with the immunotherapy drug nivolumab, according to researchers.

The unique populations of recently activated CD4+, CD8+, and CD4-CD8 double-negative cells identified in the tumors expressed specific activation markers and inhibitor receptors, according to investigators, who have published the results of their immune profiling analyses in Cellular and Molecular Gastroenterology and Hepatology.

“Importantly, these cells expressed markers of activation and tissue residence, possibly suggesting activation within the tumor,” said Daniela Di Blasi, PhD, and the others researchers, of the University of Basel in Switzerland.

A further look at tumor histology revealed an accumulation of those activated T cells in immune-inflamed HCC, according to the investigators, who added that enumeration of specific tumor-infiltrating lymphocytes could represent “a prognostic indicator of therapy responsiveness.”

However, they advised caution in interpreting the results to date: “We are aware that the analysis described here is based on a small number of patients and that validation of its prognostic value requires ad hoc prospective studies that include more patients,” they said in their report.

The researcher’s findings were based on analysis of HCC biopsies before and after treatment with the immune checkpoint inhibitor nivolumab, nontumor liver tissue biopsies, and peripheral blood samples from 36 patients, most of whom were male, and about half of whom had cirrhosis. Investigators used multiparametric flow cytometry to characterize expression of activation markers including CD137, CD150, and ICOS, among others, as well as expression of inhibitory receptors including TIGIT and PD1.

Compared with nonneoplastic liver tissue, tumor tissue was enriched with T cells expressing the activation marker CD137 and the inhibitory receptor ICOS, indicating that HCC tumor-infiltrating lymphocytes “are different from liver-resident T cells and might have immunologic relevance,” Dr. Di Blasi and coauthors said in their report.

Further analysis revealed several cell populations unique to HCC samples, the authors said, including CD4+ T cells coexpressing ICOS and TIGIT, which tended to accumulate in tumor tissue, compared with nontumor tissue and peripheral blood mononuclear cells. Those CD4+ tumor-infiltrating T cells were functionally impaired, they added, as shown by a lack of cytokine production.

Activated CD8+ T cells likewise preferentially accumulated in tumor tissue, and most of those tumor-infiltrating cells expressed CD38 and PD1. The presence of these proliferating and functional cells may contribute to local inflammation and antitumor response, according to the investigators, who also identified two unique populations of double-negative T cells, including some that expressed CD137, which they said was a marker of recent T-cell activation.

The investigators also looked at the presence of tumor-infiltrating lymphocytes correlated to the presence of mononuclear cell infiltrate in tumor tissue. They found that immune-inflamed tumors had significantly increased proliferation of unique CD4+, CD8+, and double-negative T cell populations.

Nivolumab treatment appeared to substantially reduce the proportion of impaired CD4+ T cells, while increasing the percentage of interferon gamma–producing CD38+ CD4+ T cells and also promoting enrichment of interferon gamma–producing CD38+ CD8+ cells. Those increases in release of interferon gamma may have a positive influence on antitumor immunity via modulation of immune and tumor cell functions, according to the investigators.

Not all immune-inflamed tumors responded to nivolumab treatment, suggesting that an immune-inflamed profile is “necessary but not sufficient” for clinical response to an anti-PD1 agent, noted Dr. Di Blasi and colleagues.

Taken together, the researchers said their investigations suggest the presence of unique populations of T cells that might be providing effective anti-tumor immunity.

“These studies set the point for the identification of the tumor antigens stimulating these T cells and their possible exploitation as immunotherapeutic targets in HCC,” they concluded in the report.

The study was supported by grants from the European Research Council and the Swiss Initiative in Systems Biology, among others. Dr. Di Blasi and coauthors disclosed no conflicts of interest.

SOURCE: Di Blasi D et al. Cell Mol Gastroenterol Hepatol. 2019 Aug 22. doi: 10.1016/j.jcmgh.2019.08.004.

Hepatocellular carcinoma (HCC) tissue contains several unique populations of tumor infiltrating cells, including some exhausted effector T cells that regain normal function when treated with the immunotherapy drug nivolumab, according to researchers.

The unique populations of recently activated CD4+, CD8+, and CD4-CD8 double-negative cells identified in the tumors expressed specific activation markers and inhibitor receptors, according to investigators, who have published the results of their immune profiling analyses in Cellular and Molecular Gastroenterology and Hepatology.

“Importantly, these cells expressed markers of activation and tissue residence, possibly suggesting activation within the tumor,” said Daniela Di Blasi, PhD, and the others researchers, of the University of Basel in Switzerland.

A further look at tumor histology revealed an accumulation of those activated T cells in immune-inflamed HCC, according to the investigators, who added that enumeration of specific tumor-infiltrating lymphocytes could represent “a prognostic indicator of therapy responsiveness.”

However, they advised caution in interpreting the results to date: “We are aware that the analysis described here is based on a small number of patients and that validation of its prognostic value requires ad hoc prospective studies that include more patients,” they said in their report.

The researcher’s findings were based on analysis of HCC biopsies before and after treatment with the immune checkpoint inhibitor nivolumab, nontumor liver tissue biopsies, and peripheral blood samples from 36 patients, most of whom were male, and about half of whom had cirrhosis. Investigators used multiparametric flow cytometry to characterize expression of activation markers including CD137, CD150, and ICOS, among others, as well as expression of inhibitory receptors including TIGIT and PD1.

Compared with nonneoplastic liver tissue, tumor tissue was enriched with T cells expressing the activation marker CD137 and the inhibitory receptor ICOS, indicating that HCC tumor-infiltrating lymphocytes “are different from liver-resident T cells and might have immunologic relevance,” Dr. Di Blasi and coauthors said in their report.

Further analysis revealed several cell populations unique to HCC samples, the authors said, including CD4+ T cells coexpressing ICOS and TIGIT, which tended to accumulate in tumor tissue, compared with nontumor tissue and peripheral blood mononuclear cells. Those CD4+ tumor-infiltrating T cells were functionally impaired, they added, as shown by a lack of cytokine production.

Activated CD8+ T cells likewise preferentially accumulated in tumor tissue, and most of those tumor-infiltrating cells expressed CD38 and PD1. The presence of these proliferating and functional cells may contribute to local inflammation and antitumor response, according to the investigators, who also identified two unique populations of double-negative T cells, including some that expressed CD137, which they said was a marker of recent T-cell activation.

The investigators also looked at the presence of tumor-infiltrating lymphocytes correlated to the presence of mononuclear cell infiltrate in tumor tissue. They found that immune-inflamed tumors had significantly increased proliferation of unique CD4+, CD8+, and double-negative T cell populations.

Nivolumab treatment appeared to substantially reduce the proportion of impaired CD4+ T cells, while increasing the percentage of interferon gamma–producing CD38+ CD4+ T cells and also promoting enrichment of interferon gamma–producing CD38+ CD8+ cells. Those increases in release of interferon gamma may have a positive influence on antitumor immunity via modulation of immune and tumor cell functions, according to the investigators.

Not all immune-inflamed tumors responded to nivolumab treatment, suggesting that an immune-inflamed profile is “necessary but not sufficient” for clinical response to an anti-PD1 agent, noted Dr. Di Blasi and colleagues.

Taken together, the researchers said their investigations suggest the presence of unique populations of T cells that might be providing effective anti-tumor immunity.

“These studies set the point for the identification of the tumor antigens stimulating these T cells and their possible exploitation as immunotherapeutic targets in HCC,” they concluded in the report.

The study was supported by grants from the European Research Council and the Swiss Initiative in Systems Biology, among others. Dr. Di Blasi and coauthors disclosed no conflicts of interest.

SOURCE: Di Blasi D et al. Cell Mol Gastroenterol Hepatol. 2019 Aug 22. doi: 10.1016/j.jcmgh.2019.08.004.

LAS VEGAS – The ability of bariatric surgery and substantial subsequent weight loss to cut the incidence of a variety of obesity-related cancers and other malignancies received further confirmation in results from two studies reported at a meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

Mitchel L. Zoler/MDedge News

In one study, 2,107 adults enrolled in the Longitudinal Assessment of Bariatric Surgery (LABS-2) study showed a statistically significant halving of the cancer incidence during 7 years of follow-up in patients who underwent bariatric surgery and had a reduction of at least 20% in their presurgical body mass index (BMI), compared with patients in the study who underwent bariatric surgery but lost less weight, reported Andrea M. Stroud, MD, a bariatric surgeon at the Oregon Health & Science University, Portland.

In the second study, analysis of about 1.7 million hospitalized U.S. patients in the National Inpatient Sample showed that the incidence of an obesity-related cancer was 21% higher in more than 1.4 million obese individuals (BMI, 35 kg/m² or greater) with no history of bariatric surgery, compared with nearly 247,000 people in the same database with a history of both obesity and bariatric surgery, said Juliana Henrique, MD, a bariatric surgeon at the Cleveland Clinic Florida in Weston.

The study reported by Dr. Henrique focused specifically on the 13 cancer types identified by the Centers for Disease Control and Prevention as having an incidence that links with overweight and obesity (Morb Mortal Wkly Rep. 2017;66[39]:1052-8), whereas the study presented by Dr. Stroud included all incident cancers during follow-up, but which were predominantly obesity related, with breast cancer – an obesity-related malignancy – having the highest incidence. Overall, 40% of all U.S. cancers in 2014 were obesity related, according to the CDC’s report.

Mitchel L. Zoler/MDedge News

“A number of studies have shown decreases in cancer rates after bariatric surgery, especially female cancers like breast and ovarian,” commented John Scott, MD, director of metabolic and bariatric surgery for Prism Health–Upstate in Greenville, S.C. “These two reports build on that.”

The evidence for weight loss after bariatric surgery as a means to cut the risk of a first or recurrent cancer has become strong enough for some patients to see cancer prophylaxis as a prime reason to undergo the procedure, said surgeons at the meeting.

Bariatric surgery and subsequent weight loss “is a substantial preventive factor for cancer, especially in patients who have obesity and diabetes,” commented Theresa LaMasters, MD, a bariatric surgeon in West Des Moines, Iowa. “It might not just be weight loss. It’s likely a multifactorial effect, including reduced inflammation after bariatric surgery, but weight loss is a component” of the effect, Dr. LaMasters said in an interview. It is now common for her to see patients seeking bariatric surgery because of a family or personal history of cancer. “Patients are trying to reduce their future risk” for cancer with bariatric surgery, she added.

The LABS-2 study enrolled 2,458 patients who were part of the first LABS cohort, LABS-1, but followed them longer term. The data Dr. Stroud reported came from 2,107 of the LABS-2 patients without a history of cancer, no cancer diagnosed in the first year after bariatric surgery, and longer-term follow-up of 7 years. About three-quarters of the patients underwent gastric bypass, with the rest undergoing laparoscopic gastric band placement. Nearly half of those included had diabetes. Their average BMI was 45-50 kg/m².

Dr. Stroud and associates ran an analysis that divided the populations into tertiles based on percentage of baseline body mass lost at 12 months after surgery and cancer-free survival during the 7 years after the 12-month follow-up. The incidence of cancer was 51% lower in patients who lost 20%-34% of their BMI, compared with those who lost less than 20%, a statistically significant difference, and patients who lost 35% or more of their BMI had a 31% reduced cancer rate, compared with those who lost less than 20%, a difference that was not statistically significant, Dr. Stroud reported. The patients who lost less weight after surgery mostly underwent gastric banding, whereas those who lost more mostly underwent gastric bypass.

Mitchel L. Zoler/MDedge News

The analysis reported by Dr. Henrique used data collected in the U.S. National Inpatient Sample during 2010-2014, which totaled more than 7 million patients hospitalized for cancer, including 1,423,367 with a history of obesity and 246,668 with obesity who had undergone bariatric surgery. Those without bariatric surgery had a 21% higher rate of developing obesity-related cancers after adjustment for many baseline demographic and clinical features, Dr. Henrique said. The cancer protection after bariatric surgery was especially notable in the subset of patients in the sample with a genetic predisposition to developing cancer.

LABS-1 and LABS-2 were funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Stroud and Dr. Henrique had no disclosures.

[email protected]

SOURCES: Stroud AM et al. Obesity Week, Abstract A107; Henrique J et al. Obesity Week, Abstract A108.

LAS VEGAS – The ability of bariatric surgery and substantial subsequent weight loss to cut the incidence of a variety of obesity-related cancers and other malignancies received further confirmation in results from two studies reported at a meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

Mitchel L. Zoler/MDedge News

In one study, 2,107 adults enrolled in the Longitudinal Assessment of Bariatric Surgery (LABS-2) study showed a statistically significant halving of the cancer incidence during 7 years of follow-up in patients who underwent bariatric surgery and had a reduction of at least 20% in their presurgical body mass index (BMI), compared with patients in the study who underwent bariatric surgery but lost less weight, reported Andrea M. Stroud, MD, a bariatric surgeon at the Oregon Health & Science University, Portland.

In the second study, analysis of about 1.7 million hospitalized U.S. patients in the National Inpatient Sample showed that the incidence of an obesity-related cancer was 21% higher in more than 1.4 million obese individuals (BMI, 35 kg/m² or greater) with no history of bariatric surgery, compared with nearly 247,000 people in the same database with a history of both obesity and bariatric surgery, said Juliana Henrique, MD, a bariatric surgeon at the Cleveland Clinic Florida in Weston.

The study reported by Dr. Henrique focused specifically on the 13 cancer types identified by the Centers for Disease Control and Prevention as having an incidence that links with overweight and obesity (Morb Mortal Wkly Rep. 2017;66[39]:1052-8), whereas the study presented by Dr. Stroud included all incident cancers during follow-up, but which were predominantly obesity related, with breast cancer – an obesity-related malignancy – having the highest incidence. Overall, 40% of all U.S. cancers in 2014 were obesity related, according to the CDC’s report.

Mitchel L. Zoler/MDedge News

“A number of studies have shown decreases in cancer rates after bariatric surgery, especially female cancers like breast and ovarian,” commented John Scott, MD, director of metabolic and bariatric surgery for Prism Health–Upstate in Greenville, S.C. “These two reports build on that.”

The evidence for weight loss after bariatric surgery as a means to cut the risk of a first or recurrent cancer has become strong enough for some patients to see cancer prophylaxis as a prime reason to undergo the procedure, said surgeons at the meeting.

Bariatric surgery and subsequent weight loss “is a substantial preventive factor for cancer, especially in patients who have obesity and diabetes,” commented Theresa LaMasters, MD, a bariatric surgeon in West Des Moines, Iowa. “It might not just be weight loss. It’s likely a multifactorial effect, including reduced inflammation after bariatric surgery, but weight loss is a component” of the effect, Dr. LaMasters said in an interview. It is now common for her to see patients seeking bariatric surgery because of a family or personal history of cancer. “Patients are trying to reduce their future risk” for cancer with bariatric surgery, she added.

The LABS-2 study enrolled 2,458 patients who were part of the first LABS cohort, LABS-1, but followed them longer term. The data Dr. Stroud reported came from 2,107 of the LABS-2 patients without a history of cancer, no cancer diagnosed in the first year after bariatric surgery, and longer-term follow-up of 7 years. About three-quarters of the patients underwent gastric bypass, with the rest undergoing laparoscopic gastric band placement. Nearly half of those included had diabetes. Their average BMI was 45-50 kg/m².

Dr. Stroud and associates ran an analysis that divided the populations into tertiles based on percentage of baseline body mass lost at 12 months after surgery and cancer-free survival during the 7 years after the 12-month follow-up. The incidence of cancer was 51% lower in patients who lost 20%-34% of their BMI, compared with those who lost less than 20%, a statistically significant difference, and patients who lost 35% or more of their BMI had a 31% reduced cancer rate, compared with those who lost less than 20%, a difference that was not statistically significant, Dr. Stroud reported. The patients who lost less weight after surgery mostly underwent gastric banding, whereas those who lost more mostly underwent gastric bypass.

Mitchel L. Zoler/MDedge News

The analysis reported by Dr. Henrique used data collected in the U.S. National Inpatient Sample during 2010-2014, which totaled more than 7 million patients hospitalized for cancer, including 1,423,367 with a history of obesity and 246,668 with obesity who had undergone bariatric surgery. Those without bariatric surgery had a 21% higher rate of developing obesity-related cancers after adjustment for many baseline demographic and clinical features, Dr. Henrique said. The cancer protection after bariatric surgery was especially notable in the subset of patients in the sample with a genetic predisposition to developing cancer.

LABS-1 and LABS-2 were funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Stroud and Dr. Henrique had no disclosures.

[email protected]

SOURCES: Stroud AM et al. Obesity Week, Abstract A107; Henrique J et al. Obesity Week, Abstract A108.

LAS VEGAS – The ability of bariatric surgery and substantial subsequent weight loss to cut the incidence of a variety of obesity-related cancers and other malignancies received further confirmation in results from two studies reported at a meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

Mitchel L. Zoler/MDedge News

In one study, 2,107 adults enrolled in the Longitudinal Assessment of Bariatric Surgery (LABS-2) study showed a statistically significant halving of the cancer incidence during 7 years of follow-up in patients who underwent bariatric surgery and had a reduction of at least 20% in their presurgical body mass index (BMI), compared with patients in the study who underwent bariatric surgery but lost less weight, reported Andrea M. Stroud, MD, a bariatric surgeon at the Oregon Health & Science University, Portland.

In the second study, analysis of about 1.7 million hospitalized U.S. patients in the National Inpatient Sample showed that the incidence of an obesity-related cancer was 21% higher in more than 1.4 million obese individuals (BMI, 35 kg/m² or greater) with no history of bariatric surgery, compared with nearly 247,000 people in the same database with a history of both obesity and bariatric surgery, said Juliana Henrique, MD, a bariatric surgeon at the Cleveland Clinic Florida in Weston.

The study reported by Dr. Henrique focused specifically on the 13 cancer types identified by the Centers for Disease Control and Prevention as having an incidence that links with overweight and obesity (Morb Mortal Wkly Rep. 2017;66[39]:1052-8), whereas the study presented by Dr. Stroud included all incident cancers during follow-up, but which were predominantly obesity related, with breast cancer – an obesity-related malignancy – having the highest incidence. Overall, 40% of all U.S. cancers in 2014 were obesity related, according to the CDC’s report.

Mitchel L. Zoler/MDedge News

“A number of studies have shown decreases in cancer rates after bariatric surgery, especially female cancers like breast and ovarian,” commented John Scott, MD, director of metabolic and bariatric surgery for Prism Health–Upstate in Greenville, S.C. “These two reports build on that.”

The evidence for weight loss after bariatric surgery as a means to cut the risk of a first or recurrent cancer has become strong enough for some patients to see cancer prophylaxis as a prime reason to undergo the procedure, said surgeons at the meeting.

Bariatric surgery and subsequent weight loss “is a substantial preventive factor for cancer, especially in patients who have obesity and diabetes,” commented Theresa LaMasters, MD, a bariatric surgeon in West Des Moines, Iowa. “It might not just be weight loss. It’s likely a multifactorial effect, including reduced inflammation after bariatric surgery, but weight loss is a component” of the effect, Dr. LaMasters said in an interview. It is now common for her to see patients seeking bariatric surgery because of a family or personal history of cancer. “Patients are trying to reduce their future risk” for cancer with bariatric surgery, she added.

The LABS-2 study enrolled 2,458 patients who were part of the first LABS cohort, LABS-1, but followed them longer term. The data Dr. Stroud reported came from 2,107 of the LABS-2 patients without a history of cancer, no cancer diagnosed in the first year after bariatric surgery, and longer-term follow-up of 7 years. About three-quarters of the patients underwent gastric bypass, with the rest undergoing laparoscopic gastric band placement. Nearly half of those included had diabetes. Their average BMI was 45-50 kg/m².

Dr. Stroud and associates ran an analysis that divided the populations into tertiles based on percentage of baseline body mass lost at 12 months after surgery and cancer-free survival during the 7 years after the 12-month follow-up. The incidence of cancer was 51% lower in patients who lost 20%-34% of their BMI, compared with those who lost less than 20%, a statistically significant difference, and patients who lost 35% or more of their BMI had a 31% reduced cancer rate, compared with those who lost less than 20%, a difference that was not statistically significant, Dr. Stroud reported. The patients who lost less weight after surgery mostly underwent gastric banding, whereas those who lost more mostly underwent gastric bypass.

Mitchel L. Zoler/MDedge News

The analysis reported by Dr. Henrique used data collected in the U.S. National Inpatient Sample during 2010-2014, which totaled more than 7 million patients hospitalized for cancer, including 1,423,367 with a history of obesity and 246,668 with obesity who had undergone bariatric surgery. Those without bariatric surgery had a 21% higher rate of developing obesity-related cancers after adjustment for many baseline demographic and clinical features, Dr. Henrique said. The cancer protection after bariatric surgery was especially notable in the subset of patients in the sample with a genetic predisposition to developing cancer.

LABS-1 and LABS-2 were funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Stroud and Dr. Henrique had no disclosures.

[email protected]

SOURCES: Stroud AM et al. Obesity Week, Abstract A107; Henrique J et al. Obesity Week, Abstract A108.

ORLANDO – Anti-CD5 chimeric antigen receptor (CAR) T cells can produce complete responses (CRs) in patients with relapsed or refractory T-cell malignancies, according to findings from a phase 1 trial.

Jennifer Smith/MDedge News

Three of 11 patients achieved a CR after CAR T-cell therapy, and one patient achieved a mixed response that deepened to a CR after transplant. Three responders, all of whom had T-cell lymphoma, were still alive and in CR at last follow-up.

There were no cases of severe cytokine release syndrome (CRS) or severe neurotoxicity, no serious infectious complications, and no nonhematologic grade 4 adverse events in this trial.

LaQuisa C. Hill, MD, of Baylor College of Medicine, Houston, presented these results at the annual meeting of the American Society of Hematology.

“While CD19 CAR T cells have revolutionized the treatment of relapsed/refractory B-cell malignancies, development of CAR T-cell platforms targeting T-cell-driven malignancies have been hindered by three main factors: CAR T-cell fratricide due to shared expression of target antigens leading to impaired expansion, ablation of normal T cells continuing to cause profound immunodeficiency, and the potential of transduced tumor cells providing a means of tumor escape,” Dr. Hill said.

Researchers have theorized that anti-CD5 CAR T cells can overcome these obstacles. In preclinical studies, anti-CD5 CAR T cells eliminated malignant blasts in vitro and in vivo and resulted in “limited and transient” fratricide (Blood. 2015 Aug 20;126[8]:983-92).

With this in mind, Dr. Hill and her colleagues tested CD5.28z CAR T cells in a phase 1 trial (NCT03081910). Eleven patients have been treated thus far – five with T-cell acute lymphoblastic leukemia (T-ALL), three with peripheral T-cell lymphoma (PTCL), two with angioimmunoblastic T-cell lymphoma (AITL), and one with Sézary syndrome.

The patients’ median age at baseline was 62 years (range, 21-71 years), and 63% were men. They had received a median of 5 prior therapies (range, 3-18). Two patients had relapsed after allogeneic hematopoietic stem cell transplant (HSCT), three had relapsed after autologous HSCT, and five were primary refractory.

Patients underwent lymphodepletion with fludarabine and cyclophosphamide, then received CAR T cells at doses of 1 x 10⁷ or 5 x 10⁷.
 

Response

Three lymphoma patients – two with AITL and one with PTCL – were still alive and in CR at last follow-up. The PTCL patient achieved a CR after CAR T-cell therapy and declined a subsequent HSCT. The patient has not received additional therapy and has retained the CR for 7 months.

One AITL patient achieved a CR and declined transplant as well. He relapsed after 7 months but received subsequent therapy and achieved another CR. The other AITL patient had a mixed response to CAR T-cell therapy but proceeded to allogeneic HSCT and achieved a CR that has lasted 9 months.

The remaining three lymphoma patients – two with PTCL and one with Sézary syndrome – progressed and died.

One T-ALL patient achieved a CR lasting 6 weeks, but the patient died while undergoing transplant workup. Two T-ALL patients did not respond to treatment and died. The remaining two patients progressed, and one of them died. The other patient who progressed is still alive and in CR after receiving subsequent therapy.

Factors associated with response

Dr. Hill said a shortened manufacturing process may be associated with enhanced response, as all responders received CAR T cells produced via a shorter manufacturing process. The shortened process involves freezing cells on day 4-5 post transduction, as opposed to day 7.

“While the numbers are too small to make any definitive conclusions, this seems to correlate with less terminal differentiation, which might improve potency,” Dr. Hill said. “However, additional analyses are ongoing.”

Dr. Hill also pointed out that CAR T-cell expansion was observed in all patients, with higher peak levels observed at the higher dose. In addition, CAR T-cell persistence was durable at both dose levels.

“We have been able to detect the CAR transgene at all follow-up time points, out to 9 months for some patients,” Dr. Hill said. “While limited persistence may play a role in nonresponders, it does not appear to be the only factor.”

Safety

“Surprisingly, no selective ablation of normal T cells has been observed,” Dr. Hill said. “As CAR T cells dwindled [after infusion], we were able to see recovery of normal T cells, all of which expressed normal levels of CD5. This was observed in all patients on study, except for one patient who had prolonged pancytopenia.”

Cytopenias were the most common grade 3/4 adverse events, including neutropenia (n = 8), anemia (n = 7), and thrombocytopenia (n = 5). Other grade 3/4 events included elevated aspartate aminotransferase (n = 2), hypoalbuminemia (n = 1), hyponatremia (n = 1), hypophosphatemia (n = 1), and elevated alanine aminotransferase (n = 1). There were no grade 5 adverse events.

Two patients developed grade 1 CRS, and two had grade 2 CRS. Both patients with grade 2 CRS were treated with tocilizumab, and their symptoms resolved.

One patient developed grade 2 immune effector cell-associated neurotoxicity syndrome, but this resolved with supportive care.

One patient had a central line–associated bloodstream infection (coagulase-negative staphylococci), and one had cytomegalovirus and BK virus reactivation. There were no fungal infections.

“We have demonstrated that CD5 CAR T cells can be manufactured from heavily pretreated patients with T-cell malignancies, and therapy is well tolerated,” Dr. Hill said. “We have seen strong and promising activity in T-cell lymphoma, which we hope to be able to translate to T-ALL as well.”

Dr. Hill said she and her colleagues hope to improve upon these results with a higher dose level of CD5 CAR T cells (1 x 10⁸), which the team plans to start testing soon. The researchers may also investigate other target antigens, such as CD7, as well as the use of donor-derived CAR T cells for patients who have relapsed after allogeneic HSCT.

Dr. Hill said she has no relevant disclosures. Baylor College of Medicine is sponsoring this trial.

[email protected]

SOURCE: Hill L et al. ASH 2019. Abstract 199.

ORLANDO – Anti-CD5 chimeric antigen receptor (CAR) T cells can produce complete responses (CRs) in patients with relapsed or refractory T-cell malignancies, according to findings from a phase 1 trial.

Jennifer Smith/MDedge News

Three of 11 patients achieved a CR after CAR T-cell therapy, and one patient achieved a mixed response that deepened to a CR after transplant. Three responders, all of whom had T-cell lymphoma, were still alive and in CR at last follow-up.

There were no cases of severe cytokine release syndrome (CRS) or severe neurotoxicity, no serious infectious complications, and no nonhematologic grade 4 adverse events in this trial.

LaQuisa C. Hill, MD, of Baylor College of Medicine, Houston, presented these results at the annual meeting of the American Society of Hematology.

“While CD19 CAR T cells have revolutionized the treatment of relapsed/refractory B-cell malignancies, development of CAR T-cell platforms targeting T-cell-driven malignancies have been hindered by three main factors: CAR T-cell fratricide due to shared expression of target antigens leading to impaired expansion, ablation of normal T cells continuing to cause profound immunodeficiency, and the potential of transduced tumor cells providing a means of tumor escape,” Dr. Hill said.

Researchers have theorized that anti-CD5 CAR T cells can overcome these obstacles. In preclinical studies, anti-CD5 CAR T cells eliminated malignant blasts in vitro and in vivo and resulted in “limited and transient” fratricide (Blood. 2015 Aug 20;126[8]:983-92).

With this in mind, Dr. Hill and her colleagues tested CD5.28z CAR T cells in a phase 1 trial (NCT03081910). Eleven patients have been treated thus far – five with T-cell acute lymphoblastic leukemia (T-ALL), three with peripheral T-cell lymphoma (PTCL), two with angioimmunoblastic T-cell lymphoma (AITL), and one with Sézary syndrome.

The patients’ median age at baseline was 62 years (range, 21-71 years), and 63% were men. They had received a median of 5 prior therapies (range, 3-18). Two patients had relapsed after allogeneic hematopoietic stem cell transplant (HSCT), three had relapsed after autologous HSCT, and five were primary refractory.

Patients underwent lymphodepletion with fludarabine and cyclophosphamide, then received CAR T cells at doses of 1 x 10⁷ or 5 x 10⁷.
 

Response

Three lymphoma patients – two with AITL and one with PTCL – were still alive and in CR at last follow-up. The PTCL patient achieved a CR after CAR T-cell therapy and declined a subsequent HSCT. The patient has not received additional therapy and has retained the CR for 7 months.

One AITL patient achieved a CR and declined transplant as well. He relapsed after 7 months but received subsequent therapy and achieved another CR. The other AITL patient had a mixed response to CAR T-cell therapy but proceeded to allogeneic HSCT and achieved a CR that has lasted 9 months.

The remaining three lymphoma patients – two with PTCL and one with Sézary syndrome – progressed and died.

One T-ALL patient achieved a CR lasting 6 weeks, but the patient died while undergoing transplant workup. Two T-ALL patients did not respond to treatment and died. The remaining two patients progressed, and one of them died. The other patient who progressed is still alive and in CR after receiving subsequent therapy.

Factors associated with response

Dr. Hill said a shortened manufacturing process may be associated with enhanced response, as all responders received CAR T cells produced via a shorter manufacturing process. The shortened process involves freezing cells on day 4-5 post transduction, as opposed to day 7.

“While the numbers are too small to make any definitive conclusions, this seems to correlate with less terminal differentiation, which might improve potency,” Dr. Hill said. “However, additional analyses are ongoing.”

Dr. Hill also pointed out that CAR T-cell expansion was observed in all patients, with higher peak levels observed at the higher dose. In addition, CAR T-cell persistence was durable at both dose levels.

“We have been able to detect the CAR transgene at all follow-up time points, out to 9 months for some patients,” Dr. Hill said. “While limited persistence may play a role in nonresponders, it does not appear to be the only factor.”

Safety

“Surprisingly, no selective ablation of normal T cells has been observed,” Dr. Hill said. “As CAR T cells dwindled [after infusion], we were able to see recovery of normal T cells, all of which expressed normal levels of CD5. This was observed in all patients on study, except for one patient who had prolonged pancytopenia.”

Cytopenias were the most common grade 3/4 adverse events, including neutropenia (n = 8), anemia (n = 7), and thrombocytopenia (n = 5). Other grade 3/4 events included elevated aspartate aminotransferase (n = 2), hypoalbuminemia (n = 1), hyponatremia (n = 1), hypophosphatemia (n = 1), and elevated alanine aminotransferase (n = 1). There were no grade 5 adverse events.

Two patients developed grade 1 CRS, and two had grade 2 CRS. Both patients with grade 2 CRS were treated with tocilizumab, and their symptoms resolved.

One patient developed grade 2 immune effector cell-associated neurotoxicity syndrome, but this resolved with supportive care.

One patient had a central line–associated bloodstream infection (coagulase-negative staphylococci), and one had cytomegalovirus and BK virus reactivation. There were no fungal infections.

“We have demonstrated that CD5 CAR T cells can be manufactured from heavily pretreated patients with T-cell malignancies, and therapy is well tolerated,” Dr. Hill said. “We have seen strong and promising activity in T-cell lymphoma, which we hope to be able to translate to T-ALL as well.”

Dr. Hill said she and her colleagues hope to improve upon these results with a higher dose level of CD5 CAR T cells (1 x 10⁸), which the team plans to start testing soon. The researchers may also investigate other target antigens, such as CD7, as well as the use of donor-derived CAR T cells for patients who have relapsed after allogeneic HSCT.

Dr. Hill said she has no relevant disclosures. Baylor College of Medicine is sponsoring this trial.

[email protected]

SOURCE: Hill L et al. ASH 2019. Abstract 199.

ORLANDO – Anti-CD5 chimeric antigen receptor (CAR) T cells can produce complete responses (CRs) in patients with relapsed or refractory T-cell malignancies, according to findings from a phase 1 trial.

Jennifer Smith/MDedge News

Three of 11 patients achieved a CR after CAR T-cell therapy, and one patient achieved a mixed response that deepened to a CR after transplant. Three responders, all of whom had T-cell lymphoma, were still alive and in CR at last follow-up.

There were no cases of severe cytokine release syndrome (CRS) or severe neurotoxicity, no serious infectious complications, and no nonhematologic grade 4 adverse events in this trial.

LaQuisa C. Hill, MD, of Baylor College of Medicine, Houston, presented these results at the annual meeting of the American Society of Hematology.

“While CD19 CAR T cells have revolutionized the treatment of relapsed/refractory B-cell malignancies, development of CAR T-cell platforms targeting T-cell-driven malignancies have been hindered by three main factors: CAR T-cell fratricide due to shared expression of target antigens leading to impaired expansion, ablation of normal T cells continuing to cause profound immunodeficiency, and the potential of transduced tumor cells providing a means of tumor escape,” Dr. Hill said.

Researchers have theorized that anti-CD5 CAR T cells can overcome these obstacles. In preclinical studies, anti-CD5 CAR T cells eliminated malignant blasts in vitro and in vivo and resulted in “limited and transient” fratricide (Blood. 2015 Aug 20;126[8]:983-92).

With this in mind, Dr. Hill and her colleagues tested CD5.28z CAR T cells in a phase 1 trial (NCT03081910). Eleven patients have been treated thus far – five with T-cell acute lymphoblastic leukemia (T-ALL), three with peripheral T-cell lymphoma (PTCL), two with angioimmunoblastic T-cell lymphoma (AITL), and one with Sézary syndrome.

The patients’ median age at baseline was 62 years (range, 21-71 years), and 63% were men. They had received a median of 5 prior therapies (range, 3-18). Two patients had relapsed after allogeneic hematopoietic stem cell transplant (HSCT), three had relapsed after autologous HSCT, and five were primary refractory.

Patients underwent lymphodepletion with fludarabine and cyclophosphamide, then received CAR T cells at doses of 1 x 10⁷ or 5 x 10⁷.
 

Response

Three lymphoma patients – two with AITL and one with PTCL – were still alive and in CR at last follow-up. The PTCL patient achieved a CR after CAR T-cell therapy and declined a subsequent HSCT. The patient has not received additional therapy and has retained the CR for 7 months.

One AITL patient achieved a CR and declined transplant as well. He relapsed after 7 months but received subsequent therapy and achieved another CR. The other AITL patient had a mixed response to CAR T-cell therapy but proceeded to allogeneic HSCT and achieved a CR that has lasted 9 months.

The remaining three lymphoma patients – two with PTCL and one with Sézary syndrome – progressed and died.

One T-ALL patient achieved a CR lasting 6 weeks, but the patient died while undergoing transplant workup. Two T-ALL patients did not respond to treatment and died. The remaining two patients progressed, and one of them died. The other patient who progressed is still alive and in CR after receiving subsequent therapy.

Factors associated with response

Dr. Hill said a shortened manufacturing process may be associated with enhanced response, as all responders received CAR T cells produced via a shorter manufacturing process. The shortened process involves freezing cells on day 4-5 post transduction, as opposed to day 7.

“While the numbers are too small to make any definitive conclusions, this seems to correlate with less terminal differentiation, which might improve potency,” Dr. Hill said. “However, additional analyses are ongoing.”

Dr. Hill also pointed out that CAR T-cell expansion was observed in all patients, with higher peak levels observed at the higher dose. In addition, CAR T-cell persistence was durable at both dose levels.

“We have been able to detect the CAR transgene at all follow-up time points, out to 9 months for some patients,” Dr. Hill said. “While limited persistence may play a role in nonresponders, it does not appear to be the only factor.”

Safety

“Surprisingly, no selective ablation of normal T cells has been observed,” Dr. Hill said. “As CAR T cells dwindled [after infusion], we were able to see recovery of normal T cells, all of which expressed normal levels of CD5. This was observed in all patients on study, except for one patient who had prolonged pancytopenia.”

Cytopenias were the most common grade 3/4 adverse events, including neutropenia (n = 8), anemia (n = 7), and thrombocytopenia (n = 5). Other grade 3/4 events included elevated aspartate aminotransferase (n = 2), hypoalbuminemia (n = 1), hyponatremia (n = 1), hypophosphatemia (n = 1), and elevated alanine aminotransferase (n = 1). There were no grade 5 adverse events.

Two patients developed grade 1 CRS, and two had grade 2 CRS. Both patients with grade 2 CRS were treated with tocilizumab, and their symptoms resolved.

One patient developed grade 2 immune effector cell-associated neurotoxicity syndrome, but this resolved with supportive care.

One patient had a central line–associated bloodstream infection (coagulase-negative staphylococci), and one had cytomegalovirus and BK virus reactivation. There were no fungal infections.

“We have demonstrated that CD5 CAR T cells can be manufactured from heavily pretreated patients with T-cell malignancies, and therapy is well tolerated,” Dr. Hill said. “We have seen strong and promising activity in T-cell lymphoma, which we hope to be able to translate to T-ALL as well.”

Dr. Hill said she and her colleagues hope to improve upon these results with a higher dose level of CD5 CAR T cells (1 x 10⁸), which the team plans to start testing soon. The researchers may also investigate other target antigens, such as CD7, as well as the use of donor-derived CAR T cells for patients who have relapsed after allogeneic HSCT.

Dr. Hill said she has no relevant disclosures. Baylor College of Medicine is sponsoring this trial.

[email protected]

SOURCE: Hill L et al. ASH 2019. Abstract 199.

ORLANDO – Updated results from the TRANSCEND NHL trial include survival data with lisocabtagene maraleucel (liso-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed/refractory B-cell lymphomas.

Jennifer Smith/MDedge News

The median progression-free survival (PFS) was 6.8 months, and the median overall survival was 21.1 months. PFS results were best among complete responders and among patients with primary mediastinal large B-cell lymphoma or transformed follicular lymphoma.

Jeremy S. Abramson, MD, of Massachusetts General Hospital in Boston, presented these results at the annual meeting of the American Society of Hematology.

“TRANSCEND NHL is the largest clinical study to date of CD19-directed CAR T cells in patients with relapsed/refractory aggressive B-cell lymphoma,” Dr. Abramson said.

The phase 1 trial (NCT02631044) includes 269 patients who received liso-cel. They were diagnosed with transformed follicular lymphoma (22%) or other indolent lymphoma (7%), high-grade B-cell lymphoma (13%), primary mediastinal large B-cell lymphoma (6%), grade 3B follicular lymphoma (1%), or diffuse large B-cell lymphoma not otherwise specified (51%).

At baseline, patients had received a median of three prior systemic therapies (range, one to eight). Some patients had received autologous (33%) or allogeneic (3%) transplant. Many patients were chemotherapy refractory (67%) or had never achieved a complete response to prior therapy (44%).

More than half of patients (59%) received bridging therapy during liso-cel manufacturing. All patients received lymphodepletion with fludarabine and cyclophosphamide, followed by liso-cel at 50 x 10⁶ CAR T cells, 100 x 10⁶ CAR T cells, or 150 x 10⁶ CAR T cells.

Response and survival

The median follow-up was 12.0 months. The overall response rate was 73%, and the complete response rate was 53%.

“Remissions were rapid, with a median of 1 month from CAR T-cell infusion, and durable, with a median duration of response that has not been reached and 55% of patients remaining in response at 1 year,” Dr. Abramson said.

The median PFS was 6.8 months overall, not reached for patients who achieved a complete response, 2.8 months for patients with a partial response, and 1.1 months for patients with stable disease or progressive disease.

The median PFS was not reached for patients with primary mediastinal large B-cell lymphoma or transformed follicular lymphoma, 5.0 months for high-grade B-cell lymphoma, 3.0 months for diffuse large B-cell lymphoma not otherwise specified, and 2.9 months in transformed indolent non-Hodgkin lymphoma.

The median overall survival was 21.1 months overall, not reached for patients who achieved a complete response, 9.0 months for patients who had a partial response, and 5.1 months for patients with stable disease or progressive disease.

Safety

Common treatment-emergent adverse events were neutropenia (63%), anemia (48%), fatigue (44%), nausea (33%), thrombocytopenia (31%), headache (30%), decreased appetite (28%), and diarrhea (26%).

Cytokine release syndrome (CRS) occurred in 42% of patients, and neurologic events occurred in 30%. Grade 3-4 CRS occurred in 2% of patients, and grade 3-4 neurologic events occurred in 10%. There were no cases of grade 5 CRS or neurologic events.

The median time to CRS onset was 5 days, and the median time to onset of neurologic events was 9 days. The median time to resolution of CRS and neurologic events was 5 days and 11 days, respectively.

“The low incidence of severe CRS and neurologic events and their late time of onset support using this product in a large range of patients and in the outpatient setting,” Dr. Abramson said.

There were seven grade 5 treatment-related adverse events, including diffuse alveolar damage, pulmonary hemorrhage, multiple organ dysfunction syndrome, cardiomyopathy, fludarabine leukoencephalopathy, septic shock, and progressive multifocal leukoencephalopathy.

This trial is sponsored by Bristol-Myers Squibb. Dr. Abramson reported relationships with Juno Therapeutics and Celgene, now owned by Bristol-Myers Squibb, and a range of other companies.

[email protected]

SOURCE: Abramson JS et al. ASH 2019, Abstract 241.

ORLANDO – Updated results from the TRANSCEND NHL trial include survival data with lisocabtagene maraleucel (liso-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed/refractory B-cell lymphomas.

Jennifer Smith/MDedge News

The median progression-free survival (PFS) was 6.8 months, and the median overall survival was 21.1 months. PFS results were best among complete responders and among patients with primary mediastinal large B-cell lymphoma or transformed follicular lymphoma.

Jeremy S. Abramson, MD, of Massachusetts General Hospital in Boston, presented these results at the annual meeting of the American Society of Hematology.

“TRANSCEND NHL is the largest clinical study to date of CD19-directed CAR T cells in patients with relapsed/refractory aggressive B-cell lymphoma,” Dr. Abramson said.

The phase 1 trial (NCT02631044) includes 269 patients who received liso-cel. They were diagnosed with transformed follicular lymphoma (22%) or other indolent lymphoma (7%), high-grade B-cell lymphoma (13%), primary mediastinal large B-cell lymphoma (6%), grade 3B follicular lymphoma (1%), or diffuse large B-cell lymphoma not otherwise specified (51%).

At baseline, patients had received a median of three prior systemic therapies (range, one to eight). Some patients had received autologous (33%) or allogeneic (3%) transplant. Many patients were chemotherapy refractory (67%) or had never achieved a complete response to prior therapy (44%).

More than half of patients (59%) received bridging therapy during liso-cel manufacturing. All patients received lymphodepletion with fludarabine and cyclophosphamide, followed by liso-cel at 50 x 10⁶ CAR T cells, 100 x 10⁶ CAR T cells, or 150 x 10⁶ CAR T cells.

Response and survival

The median follow-up was 12.0 months. The overall response rate was 73%, and the complete response rate was 53%.

“Remissions were rapid, with a median of 1 month from CAR T-cell infusion, and durable, with a median duration of response that has not been reached and 55% of patients remaining in response at 1 year,” Dr. Abramson said.

The median PFS was 6.8 months overall, not reached for patients who achieved a complete response, 2.8 months for patients with a partial response, and 1.1 months for patients with stable disease or progressive disease.

The median PFS was not reached for patients with primary mediastinal large B-cell lymphoma or transformed follicular lymphoma, 5.0 months for high-grade B-cell lymphoma, 3.0 months for diffuse large B-cell lymphoma not otherwise specified, and 2.9 months in transformed indolent non-Hodgkin lymphoma.

The median overall survival was 21.1 months overall, not reached for patients who achieved a complete response, 9.0 months for patients who had a partial response, and 5.1 months for patients with stable disease or progressive disease.

Safety

Common treatment-emergent adverse events were neutropenia (63%), anemia (48%), fatigue (44%), nausea (33%), thrombocytopenia (31%), headache (30%), decreased appetite (28%), and diarrhea (26%).

Cytokine release syndrome (CRS) occurred in 42% of patients, and neurologic events occurred in 30%. Grade 3-4 CRS occurred in 2% of patients, and grade 3-4 neurologic events occurred in 10%. There were no cases of grade 5 CRS or neurologic events.

The median time to CRS onset was 5 days, and the median time to onset of neurologic events was 9 days. The median time to resolution of CRS and neurologic events was 5 days and 11 days, respectively.

“The low incidence of severe CRS and neurologic events and their late time of onset support using this product in a large range of patients and in the outpatient setting,” Dr. Abramson said.

There were seven grade 5 treatment-related adverse events, including diffuse alveolar damage, pulmonary hemorrhage, multiple organ dysfunction syndrome, cardiomyopathy, fludarabine leukoencephalopathy, septic shock, and progressive multifocal leukoencephalopathy.

This trial is sponsored by Bristol-Myers Squibb. Dr. Abramson reported relationships with Juno Therapeutics and Celgene, now owned by Bristol-Myers Squibb, and a range of other companies.

[email protected]

SOURCE: Abramson JS et al. ASH 2019, Abstract 241.

ORLANDO – Updated results from the TRANSCEND NHL trial include survival data with lisocabtagene maraleucel (liso-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed/refractory B-cell lymphomas.

Jennifer Smith/MDedge News

The median progression-free survival (PFS) was 6.8 months, and the median overall survival was 21.1 months. PFS results were best among complete responders and among patients with primary mediastinal large B-cell lymphoma or transformed follicular lymphoma.

Jeremy S. Abramson, MD, of Massachusetts General Hospital in Boston, presented these results at the annual meeting of the American Society of Hematology.

“TRANSCEND NHL is the largest clinical study to date of CD19-directed CAR T cells in patients with relapsed/refractory aggressive B-cell lymphoma,” Dr. Abramson said.

The phase 1 trial (NCT02631044) includes 269 patients who received liso-cel. They were diagnosed with transformed follicular lymphoma (22%) or other indolent lymphoma (7%), high-grade B-cell lymphoma (13%), primary mediastinal large B-cell lymphoma (6%), grade 3B follicular lymphoma (1%), or diffuse large B-cell lymphoma not otherwise specified (51%).

At baseline, patients had received a median of three prior systemic therapies (range, one to eight). Some patients had received autologous (33%) or allogeneic (3%) transplant. Many patients were chemotherapy refractory (67%) or had never achieved a complete response to prior therapy (44%).

More than half of patients (59%) received bridging therapy during liso-cel manufacturing. All patients received lymphodepletion with fludarabine and cyclophosphamide, followed by liso-cel at 50 x 10⁶ CAR T cells, 100 x 10⁶ CAR T cells, or 150 x 10⁶ CAR T cells.

Response and survival

The median follow-up was 12.0 months. The overall response rate was 73%, and the complete response rate was 53%.

“Remissions were rapid, with a median of 1 month from CAR T-cell infusion, and durable, with a median duration of response that has not been reached and 55% of patients remaining in response at 1 year,” Dr. Abramson said.

The median PFS was 6.8 months overall, not reached for patients who achieved a complete response, 2.8 months for patients with a partial response, and 1.1 months for patients with stable disease or progressive disease.

The median PFS was not reached for patients with primary mediastinal large B-cell lymphoma or transformed follicular lymphoma, 5.0 months for high-grade B-cell lymphoma, 3.0 months for diffuse large B-cell lymphoma not otherwise specified, and 2.9 months in transformed indolent non-Hodgkin lymphoma.

The median overall survival was 21.1 months overall, not reached for patients who achieved a complete response, 9.0 months for patients who had a partial response, and 5.1 months for patients with stable disease or progressive disease.

Safety

Common treatment-emergent adverse events were neutropenia (63%), anemia (48%), fatigue (44%), nausea (33%), thrombocytopenia (31%), headache (30%), decreased appetite (28%), and diarrhea (26%).

Cytokine release syndrome (CRS) occurred in 42% of patients, and neurologic events occurred in 30%. Grade 3-4 CRS occurred in 2% of patients, and grade 3-4 neurologic events occurred in 10%. There were no cases of grade 5 CRS or neurologic events.

The median time to CRS onset was 5 days, and the median time to onset of neurologic events was 9 days. The median time to resolution of CRS and neurologic events was 5 days and 11 days, respectively.

“The low incidence of severe CRS and neurologic events and their late time of onset support using this product in a large range of patients and in the outpatient setting,” Dr. Abramson said.

There were seven grade 5 treatment-related adverse events, including diffuse alveolar damage, pulmonary hemorrhage, multiple organ dysfunction syndrome, cardiomyopathy, fludarabine leukoencephalopathy, septic shock, and progressive multifocal leukoencephalopathy.

This trial is sponsored by Bristol-Myers Squibb. Dr. Abramson reported relationships with Juno Therapeutics and Celgene, now owned by Bristol-Myers Squibb, and a range of other companies.

[email protected]

SOURCE: Abramson JS et al. ASH 2019, Abstract 241.