Key clinical point: A dose of 25 mg exemestane 3 times weekly was noninferior to the standard once-daily dose in decreasing serum estradiol levels in postmenopausal women with stage 0-II estrogen receptor-positive (ER+) breast cancer (BC).

Major finding: Compared with once-daily exemestane, 3-times-weekly exemestane was noninferior (difference in percentage change 2.0%; P for noninferiority = .02) whereas once-weekly exemestane was less effective in decreasing serum estradiol levels in participants who received ≥80% of the active scheduled pills and underwent blood testing as per protocol. The adverse event rate was similar across all treatment arms.

Study details: This phase 2b trial included 180 postmenopausal women with stage 0-II, ER+ BC who were randomly assigned to receive 25 mg exemestane once daily, 3 times weekly, or once weekly for 4-6 weeks before surgery.

Disclosures: This study was supported by the US National Cancer Institute and other sources. Two authors declared being principal investigators, holding stocks, or receiving partial salary support or personal fees from various sources.

Source: Serrano D et al. Efficacy of alternative dose regimens of exemestane in postmenopausal women with stage 0 to II estrogen receptor-positive breast cancer: A randomized clinical trial. JAMA Oncol. 2023 (Mar 23). Doi: 10.1001/jamaoncol.2023.0089

Key clinical point: A dose of 25 mg exemestane 3 times weekly was noninferior to the standard once-daily dose in decreasing serum estradiol levels in postmenopausal women with stage 0-II estrogen receptor-positive (ER+) breast cancer (BC).

Major finding: Compared with once-daily exemestane, 3-times-weekly exemestane was noninferior (difference in percentage change 2.0%; P for noninferiority = .02) whereas once-weekly exemestane was less effective in decreasing serum estradiol levels in participants who received ≥80% of the active scheduled pills and underwent blood testing as per protocol. The adverse event rate was similar across all treatment arms.

Study details: This phase 2b trial included 180 postmenopausal women with stage 0-II, ER+ BC who were randomly assigned to receive 25 mg exemestane once daily, 3 times weekly, or once weekly for 4-6 weeks before surgery.

Disclosures: This study was supported by the US National Cancer Institute and other sources. Two authors declared being principal investigators, holding stocks, or receiving partial salary support or personal fees from various sources.

Source: Serrano D et al. Efficacy of alternative dose regimens of exemestane in postmenopausal women with stage 0 to II estrogen receptor-positive breast cancer: A randomized clinical trial. JAMA Oncol. 2023 (Mar 23). Doi: 10.1001/jamaoncol.2023.0089

Key clinical point: A dose of 25 mg exemestane 3 times weekly was noninferior to the standard once-daily dose in decreasing serum estradiol levels in postmenopausal women with stage 0-II estrogen receptor-positive (ER+) breast cancer (BC).

Major finding: Compared with once-daily exemestane, 3-times-weekly exemestane was noninferior (difference in percentage change 2.0%; P for noninferiority = .02) whereas once-weekly exemestane was less effective in decreasing serum estradiol levels in participants who received ≥80% of the active scheduled pills and underwent blood testing as per protocol. The adverse event rate was similar across all treatment arms.

Study details: This phase 2b trial included 180 postmenopausal women with stage 0-II, ER+ BC who were randomly assigned to receive 25 mg exemestane once daily, 3 times weekly, or once weekly for 4-6 weeks before surgery.

Disclosures: This study was supported by the US National Cancer Institute and other sources. Two authors declared being principal investigators, holding stocks, or receiving partial salary support or personal fees from various sources.

Source: Serrano D et al. Efficacy of alternative dose regimens of exemestane in postmenopausal women with stage 0 to II estrogen receptor-positive breast cancer: A randomized clinical trial. JAMA Oncol. 2023 (Mar 23). Doi: 10.1001/jamaoncol.2023.0089

The sex of a red blood cell donor has no effect on the survival of a transfusion recipient, data suggest.

In a randomized clinical trial with almost 9,000 patients, the adjusted hazard ratio of death among recipients of female donors’ blood, compared with recipients of male donors’ blood, was 0.98. The data contradict the finding of previous observational studies that donor sex is associated with recipient outcomes.

“The key finding was that we actually had a null result,” study author Dean Fergusson, MD, PhD, senior scientist at the Ottawa Hospital Research Institute, said in an interview. “We went in thinking that male donor blood would confer a benefit over female donor blood, and we found that there’s absolutely no difference between the donor sexes on recipient outcomes – mortality and other major secondary outcomes,” Dr. Fergusson added.

The study was published in the New England Journal of Medicine.
 

Differences ‘don’t matter’

A 2015 article from the National Heart, Lung, and Blood Institute identified a potential effect of donor sex on transfusion recipient survival. Since then, several observational studies have suggested that donor sex may influence survival after transfusion. This research includes two large studies, one from Canada and one from the Netherlands, that reported a heightened risk of death among recipients of red-cell units from female donors or donors who had been pregnant. Other studies, however, yielded conflicting results.

“The rationale was that female blood, because of biochemical properties, different hormones, exposure to babies and other males, all led to a different product, if you will, and these subtle changes could affect the blood product in terms of shelf life and potency,” said Dr. Fergusson. “That itself would have downstream effects on the recipient.”

The current double-blind study included 8,719 patients who received transfusions from September 2018 to December 2020 at three academic medical centers in Canada. Of this group, 5,190 received male donor blood, and 3,529 received blood from female donors.

The researchers randomly assigned patients in a 60:40 ratio to male and female donor groups. Data collection and follow-up were performed by the Ottawa Hospital Data Warehouse, Canadian Blood Services, and ICES, an independent research institute. Patient characteristics were similar in both trial groups at baseline.

After an average follow-up of 11.2 months, with a maximum follow-up of 29 months, 1,141 patients in the female donor group and 1,712 in the male donor group died. The study found no statistically significant difference in overall survival between the two groups. The unadjusted HR for death, with the male group as the reference, was 0.97, and the adjusted HR was 0.98. The rates of overall survival were 58% and 56.1% in the female and male donor groups, respectively.

The study did not prove that differences in outcome based on donor sex do not exist, said Dr. Fergusson. “But those differences really don’t matter in the recipient.”

The design of the trial itself was unique, Dr. Fergusson said. After patients consented to participate and underwent randomization, the study used routinely collected data from the participating hospitals’ electronic medical records rather than collect data anew for each patient. “That had a profound effect on the efficiency of the trial. We did this trial for a cost of less than $300,000, and typically it would cost $9 million by using high-quality electronic health data.”

The study also evaluated several secondary outcomes. Recipients of female donor blood had twice the incidence of MRSA infection. In addition, an unadjusted subgroup analysis suggested a 10% lower risk of death among male patients assigned to the female donor group, compared with those assigned to the male donor group.

The risk of death was almost three times higher among patients in the female donor group who received units from donors aged 20-29.9 years (HR, 2.93). “The inconsistency of the point estimates across groups and the multiplicity of analyses increase the risk that those findings were due to chance,” according to the authors.
 

Big data

Commenting on the study, Jeannie Callum, MD, professor and director of transfusion medicine at Queen’s University, Kingston, Ont., said that the use of routinely collected data from the participating hospitals’ electronic medical records was “one of the really great things about this paper.”

This use of Big Data “allows you to do a trial like this with almost 9,000 patients without spending millions and millions of dollars to have people go through charts and record data,” she added.

Dr. Callum also pointed out some of the trial’s limitations. “One of the things that kind of detracts from the study in my mind is that they randomized everybody that was getting a transfusion, but outpatients getting a transfusion have a very low mortality rate. So, you have a group of patients that are never going to have that endpoint being included in the study, and that might’ve diluted the findings.”

About 11.4% of participants received blood from a donor group other than the one to which they had been assigned, and this factor may further dilute the findings, said Dr. Callum. “That’s a difficult thing to avoid.” She noted that a trial in which she is collaborating, called Sex Matters, may answer some of these questions about the use of female versus male donor blood.

The investigators also noted that the findings may not be generalizable to other countries. “Just because we didn’t find something in Canada with our blood production system doesn’t mean that the United States might not find it different, because how they manufacture their red blood cells for transfusion is different than how we do them in Canada,” said Dr. Callum.

Nonetheless, this study shows the potential of using Big Data in medicine. “This is the future of large randomized clinical trials to quickly answer questions,” said Dr. Callum. “In the United States, Canada, and other countries that have these large electronic medical records systems, this kind of trial would be able to be done in other centers.”

The study was funded by the Canadian Institutes of Health Research. Dr. Fergusson and Dr. Callum disclosed no relevant financial relationships.

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

The sex of a red blood cell donor has no effect on the survival of a transfusion recipient, data suggest.

In a randomized clinical trial with almost 9,000 patients, the adjusted hazard ratio of death among recipients of female donors’ blood, compared with recipients of male donors’ blood, was 0.98. The data contradict the finding of previous observational studies that donor sex is associated with recipient outcomes.

“The key finding was that we actually had a null result,” study author Dean Fergusson, MD, PhD, senior scientist at the Ottawa Hospital Research Institute, said in an interview. “We went in thinking that male donor blood would confer a benefit over female donor blood, and we found that there’s absolutely no difference between the donor sexes on recipient outcomes – mortality and other major secondary outcomes,” Dr. Fergusson added.

The study was published in the New England Journal of Medicine.
 

Differences ‘don’t matter’

A 2015 article from the National Heart, Lung, and Blood Institute identified a potential effect of donor sex on transfusion recipient survival. Since then, several observational studies have suggested that donor sex may influence survival after transfusion. This research includes two large studies, one from Canada and one from the Netherlands, that reported a heightened risk of death among recipients of red-cell units from female donors or donors who had been pregnant. Other studies, however, yielded conflicting results.

“The rationale was that female blood, because of biochemical properties, different hormones, exposure to babies and other males, all led to a different product, if you will, and these subtle changes could affect the blood product in terms of shelf life and potency,” said Dr. Fergusson. “That itself would have downstream effects on the recipient.”

The current double-blind study included 8,719 patients who received transfusions from September 2018 to December 2020 at three academic medical centers in Canada. Of this group, 5,190 received male donor blood, and 3,529 received blood from female donors.

The researchers randomly assigned patients in a 60:40 ratio to male and female donor groups. Data collection and follow-up were performed by the Ottawa Hospital Data Warehouse, Canadian Blood Services, and ICES, an independent research institute. Patient characteristics were similar in both trial groups at baseline.

After an average follow-up of 11.2 months, with a maximum follow-up of 29 months, 1,141 patients in the female donor group and 1,712 in the male donor group died. The study found no statistically significant difference in overall survival between the two groups. The unadjusted HR for death, with the male group as the reference, was 0.97, and the adjusted HR was 0.98. The rates of overall survival were 58% and 56.1% in the female and male donor groups, respectively.

The study did not prove that differences in outcome based on donor sex do not exist, said Dr. Fergusson. “But those differences really don’t matter in the recipient.”

The design of the trial itself was unique, Dr. Fergusson said. After patients consented to participate and underwent randomization, the study used routinely collected data from the participating hospitals’ electronic medical records rather than collect data anew for each patient. “That had a profound effect on the efficiency of the trial. We did this trial for a cost of less than $300,000, and typically it would cost $9 million by using high-quality electronic health data.”

The study also evaluated several secondary outcomes. Recipients of female donor blood had twice the incidence of MRSA infection. In addition, an unadjusted subgroup analysis suggested a 10% lower risk of death among male patients assigned to the female donor group, compared with those assigned to the male donor group.

The risk of death was almost three times higher among patients in the female donor group who received units from donors aged 20-29.9 years (HR, 2.93). “The inconsistency of the point estimates across groups and the multiplicity of analyses increase the risk that those findings were due to chance,” according to the authors.
 

Big data

Commenting on the study, Jeannie Callum, MD, professor and director of transfusion medicine at Queen’s University, Kingston, Ont., said that the use of routinely collected data from the participating hospitals’ electronic medical records was “one of the really great things about this paper.”

This use of Big Data “allows you to do a trial like this with almost 9,000 patients without spending millions and millions of dollars to have people go through charts and record data,” she added.

Dr. Callum also pointed out some of the trial’s limitations. “One of the things that kind of detracts from the study in my mind is that they randomized everybody that was getting a transfusion, but outpatients getting a transfusion have a very low mortality rate. So, you have a group of patients that are never going to have that endpoint being included in the study, and that might’ve diluted the findings.”

About 11.4% of participants received blood from a donor group other than the one to which they had been assigned, and this factor may further dilute the findings, said Dr. Callum. “That’s a difficult thing to avoid.” She noted that a trial in which she is collaborating, called Sex Matters, may answer some of these questions about the use of female versus male donor blood.

The investigators also noted that the findings may not be generalizable to other countries. “Just because we didn’t find something in Canada with our blood production system doesn’t mean that the United States might not find it different, because how they manufacture their red blood cells for transfusion is different than how we do them in Canada,” said Dr. Callum.

Nonetheless, this study shows the potential of using Big Data in medicine. “This is the future of large randomized clinical trials to quickly answer questions,” said Dr. Callum. “In the United States, Canada, and other countries that have these large electronic medical records systems, this kind of trial would be able to be done in other centers.”

The study was funded by the Canadian Institutes of Health Research. Dr. Fergusson and Dr. Callum disclosed no relevant financial relationships.

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

The sex of a red blood cell donor has no effect on the survival of a transfusion recipient, data suggest.

In a randomized clinical trial with almost 9,000 patients, the adjusted hazard ratio of death among recipients of female donors’ blood, compared with recipients of male donors’ blood, was 0.98. The data contradict the finding of previous observational studies that donor sex is associated with recipient outcomes.

“The key finding was that we actually had a null result,” study author Dean Fergusson, MD, PhD, senior scientist at the Ottawa Hospital Research Institute, said in an interview. “We went in thinking that male donor blood would confer a benefit over female donor blood, and we found that there’s absolutely no difference between the donor sexes on recipient outcomes – mortality and other major secondary outcomes,” Dr. Fergusson added.

The study was published in the New England Journal of Medicine.
 

Differences ‘don’t matter’

A 2015 article from the National Heart, Lung, and Blood Institute identified a potential effect of donor sex on transfusion recipient survival. Since then, several observational studies have suggested that donor sex may influence survival after transfusion. This research includes two large studies, one from Canada and one from the Netherlands, that reported a heightened risk of death among recipients of red-cell units from female donors or donors who had been pregnant. Other studies, however, yielded conflicting results.

“The rationale was that female blood, because of biochemical properties, different hormones, exposure to babies and other males, all led to a different product, if you will, and these subtle changes could affect the blood product in terms of shelf life and potency,” said Dr. Fergusson. “That itself would have downstream effects on the recipient.”

The current double-blind study included 8,719 patients who received transfusions from September 2018 to December 2020 at three academic medical centers in Canada. Of this group, 5,190 received male donor blood, and 3,529 received blood from female donors.

The researchers randomly assigned patients in a 60:40 ratio to male and female donor groups. Data collection and follow-up were performed by the Ottawa Hospital Data Warehouse, Canadian Blood Services, and ICES, an independent research institute. Patient characteristics were similar in both trial groups at baseline.

After an average follow-up of 11.2 months, with a maximum follow-up of 29 months, 1,141 patients in the female donor group and 1,712 in the male donor group died. The study found no statistically significant difference in overall survival between the two groups. The unadjusted HR for death, with the male group as the reference, was 0.97, and the adjusted HR was 0.98. The rates of overall survival were 58% and 56.1% in the female and male donor groups, respectively.

The study did not prove that differences in outcome based on donor sex do not exist, said Dr. Fergusson. “But those differences really don’t matter in the recipient.”

The design of the trial itself was unique, Dr. Fergusson said. After patients consented to participate and underwent randomization, the study used routinely collected data from the participating hospitals’ electronic medical records rather than collect data anew for each patient. “That had a profound effect on the efficiency of the trial. We did this trial for a cost of less than $300,000, and typically it would cost $9 million by using high-quality electronic health data.”

The study also evaluated several secondary outcomes. Recipients of female donor blood had twice the incidence of MRSA infection. In addition, an unadjusted subgroup analysis suggested a 10% lower risk of death among male patients assigned to the female donor group, compared with those assigned to the male donor group.

The risk of death was almost three times higher among patients in the female donor group who received units from donors aged 20-29.9 years (HR, 2.93). “The inconsistency of the point estimates across groups and the multiplicity of analyses increase the risk that those findings were due to chance,” according to the authors.
 

Big data

Commenting on the study, Jeannie Callum, MD, professor and director of transfusion medicine at Queen’s University, Kingston, Ont., said that the use of routinely collected data from the participating hospitals’ electronic medical records was “one of the really great things about this paper.”

This use of Big Data “allows you to do a trial like this with almost 9,000 patients without spending millions and millions of dollars to have people go through charts and record data,” she added.

Dr. Callum also pointed out some of the trial’s limitations. “One of the things that kind of detracts from the study in my mind is that they randomized everybody that was getting a transfusion, but outpatients getting a transfusion have a very low mortality rate. So, you have a group of patients that are never going to have that endpoint being included in the study, and that might’ve diluted the findings.”

About 11.4% of participants received blood from a donor group other than the one to which they had been assigned, and this factor may further dilute the findings, said Dr. Callum. “That’s a difficult thing to avoid.” She noted that a trial in which she is collaborating, called Sex Matters, may answer some of these questions about the use of female versus male donor blood.

The investigators also noted that the findings may not be generalizable to other countries. “Just because we didn’t find something in Canada with our blood production system doesn’t mean that the United States might not find it different, because how they manufacture their red blood cells for transfusion is different than how we do them in Canada,” said Dr. Callum.

Nonetheless, this study shows the potential of using Big Data in medicine. “This is the future of large randomized clinical trials to quickly answer questions,” said Dr. Callum. “In the United States, Canada, and other countries that have these large electronic medical records systems, this kind of trial would be able to be done in other centers.”

The study was funded by the Canadian Institutes of Health Research. Dr. Fergusson and Dr. Callum disclosed no relevant financial relationships.

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

Physical exercise is associated with a reduction in suicide attempts, new research suggests.

A meta-analysis of 17 randomized controlled trials (RCTs), which included more than 1,000 participants with mental or physical illnesses, showed there was a significant reduction in suicide attempts in participants randomly assigned to receive exercise interventions, compared with inactive controls. However, there were no differences between the exercise and the control groups in suicidal ideation or mortality.

On the other hand, there was also no significant difference in dropout rates between those randomly assigned to exercise versus inactive controls, suggesting that people with mental or physical impairments are able to adhere to exercise regimens.

“A common misconception is that patients, particularly those suffering from mental of physical illness, are not willing or motivated enough to participate in an exercise [regimen], and this has led to primary care providers underprescribing exercise to those with mental or physical illness,” lead author Nicholas Fabiano, MD, a resident in the department of psychiatry at the University of Ottawa, told this news organization.

As a result of the study findings, “we recommend that providers do not have apprehension about prescribing exercise to patients with physical or mental illness. Exercise may be an effective way to reduce suicidal behaviors” in these patients, he said.

The study was published online  in the Journal of Affective Disorders.
 

Physical, mental health strongly linked

Existing literature has “demonstrated a protective effect of physical activity on suicidal ideation in the general population,” but to date there have been no systematic reviews or meta-analyses investigating its impact on suicide-related outcomes in patients with physical or mental illness, the authors write.

“Those with mental or physical illness are at increased risk of suicide, compared to the general population,” Dr. Fabiano commented.

“We often split up ‘mental health’ and ‘physical health’ in medicine; however, I believe that the two are more on a continuum and a holistic term, such as ‘health,’ should be used instead,” he added.

He noted that mental and physical health are “inexorably intertwined” and those with physical illness are more prone to developing mental illness, whereas those with mental illness are more likely to suffer from a variety of other medical conditions. “Therefore, when treating those with mental illness, it is also imperative that we bolster one’s physical health through easily accessible activities such as exercise,” he said.

The goal of the study was to determine whether individuals with “any mental, physical, clinical, or subclinical condition” might benefit from exercise, particularly in relation to suicide-related outcomes. They searched multiple databases from inception to June 2022 to identify RCTs investigating exercise and suicidal ideation in participants with physical or mental conditions.

Of 673 studies, 17 met the inclusion criteria (total of 1,021 participants). Participants’ mean age was 42.7 years, 82% were female, and 54% were randomly assigned to an exercise intervention.

Most studies (82%) focused on clinical versus subclinical outcomes. Depression was the most commonly included condition (59%). Aerobic exercise (53%) was the most common form of exercise used in the active study groups. This was followed by mind-body exercise and strength training (53%, 17.6%, and 17.6%, respectively). The mean follow-up time was 10 weeks.
 

Reduced impulsivity

The researchers found a difference in post-intervention suicidal ideation when they compared exercise participants to all control and inactive control participants (standardized mean difference, –1.09; 95% confidence interval, –3.08 to 0.90; P = .20, k = 5). However, the difference was not statistically significant.

Similarly, there was no significant difference (P = .60) in suicidal ideation incidence for subgroup analyses that stratified data among participants with depression, sickle cell disease, and suicidality.

All-cause discontinuation also did not significantly differ between participants who were randomly assigned to exercise interventions versus all controls or inactive controls (odds ratio, 0.85; 95% CI, 0.38-1.94; P = .86, k = 12 and OR, 0.81; 95% CI, 0.25-2.68; P = .70). All-cause discontinuation also did not differ between participants randomized to exercise versus active controls (OR, 0.94; 95% CI, 0.38-2.32; P = .79, k = 3).

Likewise, there were nonsignificant differences between participants who underwent aerobic exercise and strength training (P = .20).

However, there were some nonsignificant differences when comparing participants with depression and stress who received the exercise intervention versus controls (P = .46).

There was a significant reduction in suicide attempts in individuals who participated in exercise interventions versus inactive controls (OR, 0.23; 95% CI, 0.09-0.67; P = .04, k = 2). On the other hand, there was no significant difference in mortality (P = .70).

Most of the studies (82%) were “at high risk of bias,” the authors note. In addition, the analysis was limited because the included studies were “few, underpowered, and heterogeneous.”

Dr. Fabiano hypothesized that the lack of effect on suicidal ideation or mortality is “likely due to the limited sample size.” As additional RCTs are conducted, Dr. Fabiano expects to see decreases in both suicidal ideation and suicide attempts.

The findings may “be explained by the ideation-to-action framework, which suggests that the development of suicidal ideation and the progression to suicide attempts are distinct processes with different influential factors,” he said.

Increased levels of exercise have been “shown to reduce emotional impulsivity and, as it has been shown that most suicide attempts are characterized by impulsivity and low lethality, we hypothesize that regular exercise serves as a protective factor against suicide attempts,” he said.
 

Not useful?

Commenting on the study, Fabien Legrand, PhD, a lecturer in clinical psychology, University of Reims Champagne-Ardenne, Reims, France, said that the impact of physical activity is of “particular interest” to him because it is closely linked to his research activity, where he has “been exploring the antidepressant effects of exercise for more than 15 years.”

A small pilot study conducted by Dr. Legrand and colleagues found rigorous physical activity to be helpful in reducing hopelessness in psychiatric patients, compared with controls. “This result is of particular relevance for suicidal patients, since it has long been documented that hopelessness is one of the main triggers of suicide ideation and suicide attempts,” he said.

Initially, Dr. Legrand “warmly welcomed” the current review and meta-analysis on the exercise and suicide. However, he felt that the paper fell short in accomplishing its intended goal. “After a thorough reading of the paper, I don’t think that the information provided can be used in any way,” he stated.

“The paper’s title – ‘Effects of Physical Exercise on Suicidal Ideation and Behavior’ – does not do justice to its content, since 9 of the included 17 RCTs did not measure changes in suicidal ideation and/or suicidal behavior following participation in an exercise program,” noted Dr. Legrand, who was not involved with authorship or the current analysis.

The study was funded by the University of Ottawa department of psychiatry. Dr. Fabiano declares no relevant financial relationships. The other authors’ disclosures are listed in the original article. Dr. Legrand declares no relevant financial relationships.

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

Physical exercise is associated with a reduction in suicide attempts, new research suggests.

A meta-analysis of 17 randomized controlled trials (RCTs), which included more than 1,000 participants with mental or physical illnesses, showed there was a significant reduction in suicide attempts in participants randomly assigned to receive exercise interventions, compared with inactive controls. However, there were no differences between the exercise and the control groups in suicidal ideation or mortality.

On the other hand, there was also no significant difference in dropout rates between those randomly assigned to exercise versus inactive controls, suggesting that people with mental or physical impairments are able to adhere to exercise regimens.

“A common misconception is that patients, particularly those suffering from mental of physical illness, are not willing or motivated enough to participate in an exercise [regimen], and this has led to primary care providers underprescribing exercise to those with mental or physical illness,” lead author Nicholas Fabiano, MD, a resident in the department of psychiatry at the University of Ottawa, told this news organization.

As a result of the study findings, “we recommend that providers do not have apprehension about prescribing exercise to patients with physical or mental illness. Exercise may be an effective way to reduce suicidal behaviors” in these patients, he said.

The study was published online  in the Journal of Affective Disorders.
 

Physical, mental health strongly linked

Existing literature has “demonstrated a protective effect of physical activity on suicidal ideation in the general population,” but to date there have been no systematic reviews or meta-analyses investigating its impact on suicide-related outcomes in patients with physical or mental illness, the authors write.

“Those with mental or physical illness are at increased risk of suicide, compared to the general population,” Dr. Fabiano commented.

“We often split up ‘mental health’ and ‘physical health’ in medicine; however, I believe that the two are more on a continuum and a holistic term, such as ‘health,’ should be used instead,” he added.

He noted that mental and physical health are “inexorably intertwined” and those with physical illness are more prone to developing mental illness, whereas those with mental illness are more likely to suffer from a variety of other medical conditions. “Therefore, when treating those with mental illness, it is also imperative that we bolster one’s physical health through easily accessible activities such as exercise,” he said.

The goal of the study was to determine whether individuals with “any mental, physical, clinical, or subclinical condition” might benefit from exercise, particularly in relation to suicide-related outcomes. They searched multiple databases from inception to June 2022 to identify RCTs investigating exercise and suicidal ideation in participants with physical or mental conditions.

Of 673 studies, 17 met the inclusion criteria (total of 1,021 participants). Participants’ mean age was 42.7 years, 82% were female, and 54% were randomly assigned to an exercise intervention.

Most studies (82%) focused on clinical versus subclinical outcomes. Depression was the most commonly included condition (59%). Aerobic exercise (53%) was the most common form of exercise used in the active study groups. This was followed by mind-body exercise and strength training (53%, 17.6%, and 17.6%, respectively). The mean follow-up time was 10 weeks.
 

Reduced impulsivity

The researchers found a difference in post-intervention suicidal ideation when they compared exercise participants to all control and inactive control participants (standardized mean difference, –1.09; 95% confidence interval, –3.08 to 0.90; P = .20, k = 5). However, the difference was not statistically significant.

Similarly, there was no significant difference (P = .60) in suicidal ideation incidence for subgroup analyses that stratified data among participants with depression, sickle cell disease, and suicidality.

All-cause discontinuation also did not significantly differ between participants who were randomly assigned to exercise interventions versus all controls or inactive controls (odds ratio, 0.85; 95% CI, 0.38-1.94; P = .86, k = 12 and OR, 0.81; 95% CI, 0.25-2.68; P = .70). All-cause discontinuation also did not differ between participants randomized to exercise versus active controls (OR, 0.94; 95% CI, 0.38-2.32; P = .79, k = 3).

Likewise, there were nonsignificant differences between participants who underwent aerobic exercise and strength training (P = .20).

However, there were some nonsignificant differences when comparing participants with depression and stress who received the exercise intervention versus controls (P = .46).

There was a significant reduction in suicide attempts in individuals who participated in exercise interventions versus inactive controls (OR, 0.23; 95% CI, 0.09-0.67; P = .04, k = 2). On the other hand, there was no significant difference in mortality (P = .70).

Most of the studies (82%) were “at high risk of bias,” the authors note. In addition, the analysis was limited because the included studies were “few, underpowered, and heterogeneous.”

Dr. Fabiano hypothesized that the lack of effect on suicidal ideation or mortality is “likely due to the limited sample size.” As additional RCTs are conducted, Dr. Fabiano expects to see decreases in both suicidal ideation and suicide attempts.

The findings may “be explained by the ideation-to-action framework, which suggests that the development of suicidal ideation and the progression to suicide attempts are distinct processes with different influential factors,” he said.

Increased levels of exercise have been “shown to reduce emotional impulsivity and, as it has been shown that most suicide attempts are characterized by impulsivity and low lethality, we hypothesize that regular exercise serves as a protective factor against suicide attempts,” he said.
 

Not useful?

Commenting on the study, Fabien Legrand, PhD, a lecturer in clinical psychology, University of Reims Champagne-Ardenne, Reims, France, said that the impact of physical activity is of “particular interest” to him because it is closely linked to his research activity, where he has “been exploring the antidepressant effects of exercise for more than 15 years.”

A small pilot study conducted by Dr. Legrand and colleagues found rigorous physical activity to be helpful in reducing hopelessness in psychiatric patients, compared with controls. “This result is of particular relevance for suicidal patients, since it has long been documented that hopelessness is one of the main triggers of suicide ideation and suicide attempts,” he said.

Initially, Dr. Legrand “warmly welcomed” the current review and meta-analysis on the exercise and suicide. However, he felt that the paper fell short in accomplishing its intended goal. “After a thorough reading of the paper, I don’t think that the information provided can be used in any way,” he stated.

“The paper’s title – ‘Effects of Physical Exercise on Suicidal Ideation and Behavior’ – does not do justice to its content, since 9 of the included 17 RCTs did not measure changes in suicidal ideation and/or suicidal behavior following participation in an exercise program,” noted Dr. Legrand, who was not involved with authorship or the current analysis.

The study was funded by the University of Ottawa department of psychiatry. Dr. Fabiano declares no relevant financial relationships. The other authors’ disclosures are listed in the original article. Dr. Legrand declares no relevant financial relationships.

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

Physical exercise is associated with a reduction in suicide attempts, new research suggests.

A meta-analysis of 17 randomized controlled trials (RCTs), which included more than 1,000 participants with mental or physical illnesses, showed there was a significant reduction in suicide attempts in participants randomly assigned to receive exercise interventions, compared with inactive controls. However, there were no differences between the exercise and the control groups in suicidal ideation or mortality.

On the other hand, there was also no significant difference in dropout rates between those randomly assigned to exercise versus inactive controls, suggesting that people with mental or physical impairments are able to adhere to exercise regimens.

“A common misconception is that patients, particularly those suffering from mental of physical illness, are not willing or motivated enough to participate in an exercise [regimen], and this has led to primary care providers underprescribing exercise to those with mental or physical illness,” lead author Nicholas Fabiano, MD, a resident in the department of psychiatry at the University of Ottawa, told this news organization.

As a result of the study findings, “we recommend that providers do not have apprehension about prescribing exercise to patients with physical or mental illness. Exercise may be an effective way to reduce suicidal behaviors” in these patients, he said.

The study was published online  in the Journal of Affective Disorders.
 

Physical, mental health strongly linked

Existing literature has “demonstrated a protective effect of physical activity on suicidal ideation in the general population,” but to date there have been no systematic reviews or meta-analyses investigating its impact on suicide-related outcomes in patients with physical or mental illness, the authors write.

“Those with mental or physical illness are at increased risk of suicide, compared to the general population,” Dr. Fabiano commented.

“We often split up ‘mental health’ and ‘physical health’ in medicine; however, I believe that the two are more on a continuum and a holistic term, such as ‘health,’ should be used instead,” he added.

He noted that mental and physical health are “inexorably intertwined” and those with physical illness are more prone to developing mental illness, whereas those with mental illness are more likely to suffer from a variety of other medical conditions. “Therefore, when treating those with mental illness, it is also imperative that we bolster one’s physical health through easily accessible activities such as exercise,” he said.

The goal of the study was to determine whether individuals with “any mental, physical, clinical, or subclinical condition” might benefit from exercise, particularly in relation to suicide-related outcomes. They searched multiple databases from inception to June 2022 to identify RCTs investigating exercise and suicidal ideation in participants with physical or mental conditions.

Of 673 studies, 17 met the inclusion criteria (total of 1,021 participants). Participants’ mean age was 42.7 years, 82% were female, and 54% were randomly assigned to an exercise intervention.

Most studies (82%) focused on clinical versus subclinical outcomes. Depression was the most commonly included condition (59%). Aerobic exercise (53%) was the most common form of exercise used in the active study groups. This was followed by mind-body exercise and strength training (53%, 17.6%, and 17.6%, respectively). The mean follow-up time was 10 weeks.
 

Reduced impulsivity

The researchers found a difference in post-intervention suicidal ideation when they compared exercise participants to all control and inactive control participants (standardized mean difference, –1.09; 95% confidence interval, –3.08 to 0.90; P = .20, k = 5). However, the difference was not statistically significant.

Similarly, there was no significant difference (P = .60) in suicidal ideation incidence for subgroup analyses that stratified data among participants with depression, sickle cell disease, and suicidality.

All-cause discontinuation also did not significantly differ between participants who were randomly assigned to exercise interventions versus all controls or inactive controls (odds ratio, 0.85; 95% CI, 0.38-1.94; P = .86, k = 12 and OR, 0.81; 95% CI, 0.25-2.68; P = .70). All-cause discontinuation also did not differ between participants randomized to exercise versus active controls (OR, 0.94; 95% CI, 0.38-2.32; P = .79, k = 3).

Likewise, there were nonsignificant differences between participants who underwent aerobic exercise and strength training (P = .20).

However, there were some nonsignificant differences when comparing participants with depression and stress who received the exercise intervention versus controls (P = .46).

There was a significant reduction in suicide attempts in individuals who participated in exercise interventions versus inactive controls (OR, 0.23; 95% CI, 0.09-0.67; P = .04, k = 2). On the other hand, there was no significant difference in mortality (P = .70).

Most of the studies (82%) were “at high risk of bias,” the authors note. In addition, the analysis was limited because the included studies were “few, underpowered, and heterogeneous.”

Dr. Fabiano hypothesized that the lack of effect on suicidal ideation or mortality is “likely due to the limited sample size.” As additional RCTs are conducted, Dr. Fabiano expects to see decreases in both suicidal ideation and suicide attempts.

The findings may “be explained by the ideation-to-action framework, which suggests that the development of suicidal ideation and the progression to suicide attempts are distinct processes with different influential factors,” he said.

Increased levels of exercise have been “shown to reduce emotional impulsivity and, as it has been shown that most suicide attempts are characterized by impulsivity and low lethality, we hypothesize that regular exercise serves as a protective factor against suicide attempts,” he said.
 

Not useful?

Commenting on the study, Fabien Legrand, PhD, a lecturer in clinical psychology, University of Reims Champagne-Ardenne, Reims, France, said that the impact of physical activity is of “particular interest” to him because it is closely linked to his research activity, where he has “been exploring the antidepressant effects of exercise for more than 15 years.”

A small pilot study conducted by Dr. Legrand and colleagues found rigorous physical activity to be helpful in reducing hopelessness in psychiatric patients, compared with controls. “This result is of particular relevance for suicidal patients, since it has long been documented that hopelessness is one of the main triggers of suicide ideation and suicide attempts,” he said.

Initially, Dr. Legrand “warmly welcomed” the current review and meta-analysis on the exercise and suicide. However, he felt that the paper fell short in accomplishing its intended goal. “After a thorough reading of the paper, I don’t think that the information provided can be used in any way,” he stated.

“The paper’s title – ‘Effects of Physical Exercise on Suicidal Ideation and Behavior’ – does not do justice to its content, since 9 of the included 17 RCTs did not measure changes in suicidal ideation and/or suicidal behavior following participation in an exercise program,” noted Dr. Legrand, who was not involved with authorship or the current analysis.

The study was funded by the University of Ottawa department of psychiatry. Dr. Fabiano declares no relevant financial relationships. The other authors’ disclosures are listed in the original article. Dr. Legrand declares no relevant financial relationships.

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

Key clinical point: Polatuzumab vedotin (Pola)-rituximab-cyclophosphamide, doxorubicin, and prednisone (R-CHP) compared with other novel regimens prolongs progression-free survival (PFS) in patients with previously untreated activated B-cell (ABC)-type diffuse large B-cell lymphoma (DLBCL).

Major finding: Pola-R-CHP prolonged PFS in patients with ABC-type DLBCL compared with rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)+bortezomib (hazard ratio [HR] 0.52; P  =  .02); R-CHOP+ibrutinib (HR 0.43; P  =  .001), R-CHOP+lenalidomide (HR 0.51; P  =  .009), obinutuzumab-CHOP (HR 0.46; P  =  .008), R-CHOP (HR 0.40; P < .001), and bortezomib, rituximab, and cyclophosphamide (HR 0.44; P  =  .07). Pola-R-CHP had no PFS benefit in patients with germinal center B-cell (GCB)-type DLBCL.

Study details: This was a network meta-analysis of 12 randomized controlled trials involving 8376 patients with previously untreated ABC- or GCB-type DLBCL who received Pola-R-CHP or other regimens.

Disclosures: This study did not report the funding source. The authors declared no conflicts of interest.

Source: Sheng Z et al. Superiority of polatuzumab vedotin over other novel agents in previously untreated ABC‑type diffuse large B‑cell lymphoma: A network meta‑analysis of 20 RCTs. Ann Hematol. 2023;102:1011-1017 (Mar 22). Doi: 10.1007/s00277-023-05161-1

Key clinical point: Polatuzumab vedotin (Pola)-rituximab-cyclophosphamide, doxorubicin, and prednisone (R-CHP) compared with other novel regimens prolongs progression-free survival (PFS) in patients with previously untreated activated B-cell (ABC)-type diffuse large B-cell lymphoma (DLBCL).

Major finding: Pola-R-CHP prolonged PFS in patients with ABC-type DLBCL compared with rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)+bortezomib (hazard ratio [HR] 0.52; P  =  .02); R-CHOP+ibrutinib (HR 0.43; P  =  .001), R-CHOP+lenalidomide (HR 0.51; P  =  .009), obinutuzumab-CHOP (HR 0.46; P  =  .008), R-CHOP (HR 0.40; P < .001), and bortezomib, rituximab, and cyclophosphamide (HR 0.44; P  =  .07). Pola-R-CHP had no PFS benefit in patients with germinal center B-cell (GCB)-type DLBCL.

Study details: This was a network meta-analysis of 12 randomized controlled trials involving 8376 patients with previously untreated ABC- or GCB-type DLBCL who received Pola-R-CHP or other regimens.

Disclosures: This study did not report the funding source. The authors declared no conflicts of interest.

Source: Sheng Z et al. Superiority of polatuzumab vedotin over other novel agents in previously untreated ABC‑type diffuse large B‑cell lymphoma: A network meta‑analysis of 20 RCTs. Ann Hematol. 2023;102:1011-1017 (Mar 22). Doi: 10.1007/s00277-023-05161-1

Key clinical point: Polatuzumab vedotin (Pola)-rituximab-cyclophosphamide, doxorubicin, and prednisone (R-CHP) compared with other novel regimens prolongs progression-free survival (PFS) in patients with previously untreated activated B-cell (ABC)-type diffuse large B-cell lymphoma (DLBCL).

Major finding: Pola-R-CHP prolonged PFS in patients with ABC-type DLBCL compared with rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)+bortezomib (hazard ratio [HR] 0.52; P  =  .02); R-CHOP+ibrutinib (HR 0.43; P  =  .001), R-CHOP+lenalidomide (HR 0.51; P  =  .009), obinutuzumab-CHOP (HR 0.46; P  =  .008), R-CHOP (HR 0.40; P < .001), and bortezomib, rituximab, and cyclophosphamide (HR 0.44; P  =  .07). Pola-R-CHP had no PFS benefit in patients with germinal center B-cell (GCB)-type DLBCL.

Study details: This was a network meta-analysis of 12 randomized controlled trials involving 8376 patients with previously untreated ABC- or GCB-type DLBCL who received Pola-R-CHP or other regimens.

Disclosures: This study did not report the funding source. The authors declared no conflicts of interest.

Source: Sheng Z et al. Superiority of polatuzumab vedotin over other novel agents in previously untreated ABC‑type diffuse large B‑cell lymphoma: A network meta‑analysis of 20 RCTs. Ann Hematol. 2023;102:1011-1017 (Mar 22). Doi: 10.1007/s00277-023-05161-1

Key clinical point: The addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) confers a survival advantage over R-CHOP in patients with activated B-cell (ABC)- and molecular high grade (MHG)-type diffuse large B-cell lymphoma (DLBCL).

Major finding: Bortezomib-R-CHOP vs R-CHOP significantly improved 60-month progression-free survival (PFS) in the ABC (adjusted hazard ratio [aHR] 0.65; P  =  .041) and MHG (aHR 0.46; P  =  .011) groups, and overall survival (OS) in the ABC group (aHR 0.58; P  =  .032). The germinal center B-cell (GCB) group showed no significant difference in PFS or OS.

Study details: This updated retrospective analysis of the phase 3 REMoDL-B study included 801 adult patients with DLBCL (ABC, MHG, or GCB subtype) who were randomly assigned to receive 2-6 cycles of R-CHOP (n = 407) or bortezomib-R-CHOP (n = 394) after one cycle of R-CHOP.

Disclosures: This study was supported by a grant from Janssen-Cilag and Cancer Research UK. Some authors reported ties with various organizations, including Janssen.

Source: Davies AJ et al. Differential efficacy from the addition of bortezomib to r-chop in diffuse large B-cell lymphoma according to the molecular subgroup in the REMoDL-B study with a 5-year follow-up. J Clin Oncol. 2023 (Mar 27). Doi: 10.1200/JCO.23.00033

Key clinical point: The addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) confers a survival advantage over R-CHOP in patients with activated B-cell (ABC)- and molecular high grade (MHG)-type diffuse large B-cell lymphoma (DLBCL).

Major finding: Bortezomib-R-CHOP vs R-CHOP significantly improved 60-month progression-free survival (PFS) in the ABC (adjusted hazard ratio [aHR] 0.65; P  =  .041) and MHG (aHR 0.46; P  =  .011) groups, and overall survival (OS) in the ABC group (aHR 0.58; P  =  .032). The germinal center B-cell (GCB) group showed no significant difference in PFS or OS.

Study details: This updated retrospective analysis of the phase 3 REMoDL-B study included 801 adult patients with DLBCL (ABC, MHG, or GCB subtype) who were randomly assigned to receive 2-6 cycles of R-CHOP (n = 407) or bortezomib-R-CHOP (n = 394) after one cycle of R-CHOP.

Disclosures: This study was supported by a grant from Janssen-Cilag and Cancer Research UK. Some authors reported ties with various organizations, including Janssen.

Source: Davies AJ et al. Differential efficacy from the addition of bortezomib to r-chop in diffuse large B-cell lymphoma according to the molecular subgroup in the REMoDL-B study with a 5-year follow-up. J Clin Oncol. 2023 (Mar 27). Doi: 10.1200/JCO.23.00033

Key clinical point: The addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) confers a survival advantage over R-CHOP in patients with activated B-cell (ABC)- and molecular high grade (MHG)-type diffuse large B-cell lymphoma (DLBCL).

Major finding: Bortezomib-R-CHOP vs R-CHOP significantly improved 60-month progression-free survival (PFS) in the ABC (adjusted hazard ratio [aHR] 0.65; P  =  .041) and MHG (aHR 0.46; P  =  .011) groups, and overall survival (OS) in the ABC group (aHR 0.58; P  =  .032). The germinal center B-cell (GCB) group showed no significant difference in PFS or OS.

Study details: This updated retrospective analysis of the phase 3 REMoDL-B study included 801 adult patients with DLBCL (ABC, MHG, or GCB subtype) who were randomly assigned to receive 2-6 cycles of R-CHOP (n = 407) or bortezomib-R-CHOP (n = 394) after one cycle of R-CHOP.

Disclosures: This study was supported by a grant from Janssen-Cilag and Cancer Research UK. Some authors reported ties with various organizations, including Janssen.

Source: Davies AJ et al. Differential efficacy from the addition of bortezomib to r-chop in diffuse large B-cell lymphoma according to the molecular subgroup in the REMoDL-B study with a 5-year follow-up. J Clin Oncol. 2023 (Mar 27). Doi: 10.1200/JCO.23.00033

Key clinical point: Compared with idelalisib+rituximab (R-idela), ibrutinib significantly prolonged survival and was associated with lower treatment discontinuation rates in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) in routine practice.

Major finding: The ibrutinib vs R-idela group had significantly longer median progression-free survival (40.5 vs 22.0 months; hazard ratio [HR] 0.55; P < .001) and overall survival (54.4 vs 37.7 months; HR 0.73; P  =  .040) and lower rates of treatment discontinuation due to toxicity (22.5% vs 39.8%) and CLL progression (11.1% vs 27.5%).

Study details: This real-world retrospective study included 415 patients with relapsed or refractory CLL from the Chronic Lymphocytic Leukemia Patients Registry who received R-idela (n = 171) or ibrutinib (n = 244).

Disclosures: This study was funded by grants from the Ministry of Health, Czech Republic, and Programme Cooperation, Research Area ONCO. Some authors reported ties with various organizations.

Source: Spacek M et al for the Czech CLL Study Group. Idelalisib plus rituximab versus ibrutinib in the treatment of relapsed/refractory chronic lymphocytic leukaemia: A real-world analysis from the Chronic Lymphocytic Leukemia Patients Registry (CLLEAR). Br J Haematol. 2023 (Mar 27). Doi: 10.1111/bjh.18736

Key clinical point: Compared with idelalisib+rituximab (R-idela), ibrutinib significantly prolonged survival and was associated with lower treatment discontinuation rates in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) in routine practice.

Major finding: The ibrutinib vs R-idela group had significantly longer median progression-free survival (40.5 vs 22.0 months; hazard ratio [HR] 0.55; P < .001) and overall survival (54.4 vs 37.7 months; HR 0.73; P  =  .040) and lower rates of treatment discontinuation due to toxicity (22.5% vs 39.8%) and CLL progression (11.1% vs 27.5%).

Study details: This real-world retrospective study included 415 patients with relapsed or refractory CLL from the Chronic Lymphocytic Leukemia Patients Registry who received R-idela (n = 171) or ibrutinib (n = 244).

Disclosures: This study was funded by grants from the Ministry of Health, Czech Republic, and Programme Cooperation, Research Area ONCO. Some authors reported ties with various organizations.

Source: Spacek M et al for the Czech CLL Study Group. Idelalisib plus rituximab versus ibrutinib in the treatment of relapsed/refractory chronic lymphocytic leukaemia: A real-world analysis from the Chronic Lymphocytic Leukemia Patients Registry (CLLEAR). Br J Haematol. 2023 (Mar 27). Doi: 10.1111/bjh.18736

Key clinical point: Compared with idelalisib+rituximab (R-idela), ibrutinib significantly prolonged survival and was associated with lower treatment discontinuation rates in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) in routine practice.

Major finding: The ibrutinib vs R-idela group had significantly longer median progression-free survival (40.5 vs 22.0 months; hazard ratio [HR] 0.55; P < .001) and overall survival (54.4 vs 37.7 months; HR 0.73; P  =  .040) and lower rates of treatment discontinuation due to toxicity (22.5% vs 39.8%) and CLL progression (11.1% vs 27.5%).

Study details: This real-world retrospective study included 415 patients with relapsed or refractory CLL from the Chronic Lymphocytic Leukemia Patients Registry who received R-idela (n = 171) or ibrutinib (n = 244).

Disclosures: This study was funded by grants from the Ministry of Health, Czech Republic, and Programme Cooperation, Research Area ONCO. Some authors reported ties with various organizations.

Source: Spacek M et al for the Czech CLL Study Group. Idelalisib plus rituximab versus ibrutinib in the treatment of relapsed/refractory chronic lymphocytic leukaemia: A real-world analysis from the Chronic Lymphocytic Leukemia Patients Registry (CLLEAR). Br J Haematol. 2023 (Mar 27). Doi: 10.1111/bjh.18736

Key clinical point: Chimeric antigen receptor (CAR)-T cell therapy after lymphodepletion led to similar survival outcomes and toxicity rates in patients with nodal (ND) and extra nodal (EN) diffuse large B-cell lymphoma (DLBCL), with outcomes being significantly worse in patients with >2 vs <3 EN sites at lymphodepletion.

Major finding: After a median follow-up of 7.5 months, patients with EN and ND DLBCL had similar median progression-free survival (PFS; 10.76 and 14.1 months, respectively; P  =  .126), overall survival (OS; 15.36 and 18.4 months, respectively; P  =  .100), and treatment-related toxicity rates. Patients with <3 vs >2 EN sites had significantly longer median PFS (P  =  .01) and OS (P  =  .05).

Study details: This real-world retrospective multicenter study included 126 patients with DLBCL of EN (n = 72) or ND (n = 42) origin who underwent lymphodepletion followed by CAR-T cell infusion with tisagenlecleucel or axicabtagene ciloleucel.

Disclosures: No information on the source of funding was provided. The authors declared no conflicts of interest.

Source: Katz OB et al. Response rates of extra-nodal diffuse large B cell lymphoma to anti CD19-CAR T cells: A real word retrospective multi-center study. Eur J Haematol. 2023 (Mar 25). Doi: 10.1111/ejh.13968

Key clinical point: Chimeric antigen receptor (CAR)-T cell therapy after lymphodepletion led to similar survival outcomes and toxicity rates in patients with nodal (ND) and extra nodal (EN) diffuse large B-cell lymphoma (DLBCL), with outcomes being significantly worse in patients with >2 vs <3 EN sites at lymphodepletion.

Major finding: After a median follow-up of 7.5 months, patients with EN and ND DLBCL had similar median progression-free survival (PFS; 10.76 and 14.1 months, respectively; P  =  .126), overall survival (OS; 15.36 and 18.4 months, respectively; P  =  .100), and treatment-related toxicity rates. Patients with <3 vs >2 EN sites had significantly longer median PFS (P  =  .01) and OS (P  =  .05).

Study details: This real-world retrospective multicenter study included 126 patients with DLBCL of EN (n = 72) or ND (n = 42) origin who underwent lymphodepletion followed by CAR-T cell infusion with tisagenlecleucel or axicabtagene ciloleucel.

Disclosures: No information on the source of funding was provided. The authors declared no conflicts of interest.

Source: Katz OB et al. Response rates of extra-nodal diffuse large B cell lymphoma to anti CD19-CAR T cells: A real word retrospective multi-center study. Eur J Haematol. 2023 (Mar 25). Doi: 10.1111/ejh.13968

Key clinical point: Chimeric antigen receptor (CAR)-T cell therapy after lymphodepletion led to similar survival outcomes and toxicity rates in patients with nodal (ND) and extra nodal (EN) diffuse large B-cell lymphoma (DLBCL), with outcomes being significantly worse in patients with >2 vs <3 EN sites at lymphodepletion.

Major finding: After a median follow-up of 7.5 months, patients with EN and ND DLBCL had similar median progression-free survival (PFS; 10.76 and 14.1 months, respectively; P  =  .126), overall survival (OS; 15.36 and 18.4 months, respectively; P  =  .100), and treatment-related toxicity rates. Patients with <3 vs >2 EN sites had significantly longer median PFS (P  =  .01) and OS (P  =  .05).

Study details: This real-world retrospective multicenter study included 126 patients with DLBCL of EN (n = 72) or ND (n = 42) origin who underwent lymphodepletion followed by CAR-T cell infusion with tisagenlecleucel or axicabtagene ciloleucel.

Disclosures: No information on the source of funding was provided. The authors declared no conflicts of interest.

Source: Katz OB et al. Response rates of extra-nodal diffuse large B cell lymphoma to anti CD19-CAR T cells: A real word retrospective multi-center study. Eur J Haematol. 2023 (Mar 25). Doi: 10.1111/ejh.13968

Key clinical point: Sufficiently fit older patients with high-risk diffuse large B-cell lymphoma (DLBCL) achieve favorable outcomes with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R); patients with a poor performance status (PS) develop unacceptable toxicity and require less intensive therapy.

Major finding: At 3 years, the progression-free survival (PFS) and overall survival (OS) rates were 53% and 58%, respectively, and the treatment-related mortality (TRM) rate was 13%. The 3-year PFS (58% vs 32%; P < .001) and OS (64% vs 33%; P  =  .007) rates were significantly higher and TRM rates were significantly lower (6% vs 43%; P < .001) among patients with PS 0-2 vs 3-4.

Study details: This multicenter retrospective real-life study included 120 patients aged ≥60 years with newly diagnosed high-risk DLBCL treated with a median of 6 DA-EPOCH-R cycles per patient.

Disclosures: No information on the source of funding or conflicts of interest was provided.

Source: Mitrovic Z et al. Dose-adjusted EPOCH and rituximab (DA-EPOCH-R) in older patients with high-risk aggressive diffuse large B-cell lymphoma: A real-life multicenter study by the Croatian Cooperative Group for Hematologic diseases (KroHem). Eur J Haematol. 2023 (Mar 20). Doi: 10.1111/ejh.13957

Key clinical point: Sufficiently fit older patients with high-risk diffuse large B-cell lymphoma (DLBCL) achieve favorable outcomes with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R); patients with a poor performance status (PS) develop unacceptable toxicity and require less intensive therapy.

Major finding: At 3 years, the progression-free survival (PFS) and overall survival (OS) rates were 53% and 58%, respectively, and the treatment-related mortality (TRM) rate was 13%. The 3-year PFS (58% vs 32%; P < .001) and OS (64% vs 33%; P  =  .007) rates were significantly higher and TRM rates were significantly lower (6% vs 43%; P < .001) among patients with PS 0-2 vs 3-4.

Study details: This multicenter retrospective real-life study included 120 patients aged ≥60 years with newly diagnosed high-risk DLBCL treated with a median of 6 DA-EPOCH-R cycles per patient.

Disclosures: No information on the source of funding or conflicts of interest was provided.

Source: Mitrovic Z et al. Dose-adjusted EPOCH and rituximab (DA-EPOCH-R) in older patients with high-risk aggressive diffuse large B-cell lymphoma: A real-life multicenter study by the Croatian Cooperative Group for Hematologic diseases (KroHem). Eur J Haematol. 2023 (Mar 20). Doi: 10.1111/ejh.13957

Key clinical point: Sufficiently fit older patients with high-risk diffuse large B-cell lymphoma (DLBCL) achieve favorable outcomes with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R); patients with a poor performance status (PS) develop unacceptable toxicity and require less intensive therapy.

Major finding: At 3 years, the progression-free survival (PFS) and overall survival (OS) rates were 53% and 58%, respectively, and the treatment-related mortality (TRM) rate was 13%. The 3-year PFS (58% vs 32%; P < .001) and OS (64% vs 33%; P  =  .007) rates were significantly higher and TRM rates were significantly lower (6% vs 43%; P < .001) among patients with PS 0-2 vs 3-4.

Study details: This multicenter retrospective real-life study included 120 patients aged ≥60 years with newly diagnosed high-risk DLBCL treated with a median of 6 DA-EPOCH-R cycles per patient.

Disclosures: No information on the source of funding or conflicts of interest was provided.

Source: Mitrovic Z et al. Dose-adjusted EPOCH and rituximab (DA-EPOCH-R) in older patients with high-risk aggressive diffuse large B-cell lymphoma: A real-life multicenter study by the Croatian Cooperative Group for Hematologic diseases (KroHem). Eur J Haematol. 2023 (Mar 20). Doi: 10.1111/ejh.13957

Key clinical point: Axicabtagene ciloleucel (axi-cel) is an effective second-line curative-intent therapy with a manageable safety profile for patients aged ≥65 years with relapsed or refractory large B-cell lymphoma (LBCL).

Major finding: At a median follow-up of 24.3 months, the median event-free survival was significantly longer with axi-cel vs standard of care (SOC; 21.5 vs 2.5 months; hazard ratio 0.276; descriptive P < .0001). The grade ≥3 treatment-emergent adverse event rates were 94% and 82% with axi-cel and SOC, respectively.

Study details: Findings are from a preplanned analysis of 109 patients aged ≥65 years with relapsed or refractory LBCL from the ZUMA-7 trial who were randomly assigned to receive second-line axi-cel (n = 51) or SOC (n = 58; 2-3 cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation).

Disclosures: This study was supported by Kite, a Gilead Company. Some authors reported ties with various organizations, including Kite and Gilead.

Source: Westin JR et al. Safety and efficacy of axicabtagene ciloleucel versus standard of care in patients 65 years of age or older with relapsed/refractory large B-cell lymphoma. Clin Cancer Res. 2023 (Mar 31). Doi: 10.1158/1078-0432.CCR-22-3136

Key clinical point: Axicabtagene ciloleucel (axi-cel) is an effective second-line curative-intent therapy with a manageable safety profile for patients aged ≥65 years with relapsed or refractory large B-cell lymphoma (LBCL).

Major finding: At a median follow-up of 24.3 months, the median event-free survival was significantly longer with axi-cel vs standard of care (SOC; 21.5 vs 2.5 months; hazard ratio 0.276; descriptive P < .0001). The grade ≥3 treatment-emergent adverse event rates were 94% and 82% with axi-cel and SOC, respectively.

Study details: Findings are from a preplanned analysis of 109 patients aged ≥65 years with relapsed or refractory LBCL from the ZUMA-7 trial who were randomly assigned to receive second-line axi-cel (n = 51) or SOC (n = 58; 2-3 cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation).

Disclosures: This study was supported by Kite, a Gilead Company. Some authors reported ties with various organizations, including Kite and Gilead.

Source: Westin JR et al. Safety and efficacy of axicabtagene ciloleucel versus standard of care in patients 65 years of age or older with relapsed/refractory large B-cell lymphoma. Clin Cancer Res. 2023 (Mar 31). Doi: 10.1158/1078-0432.CCR-22-3136

Key clinical point: Axicabtagene ciloleucel (axi-cel) is an effective second-line curative-intent therapy with a manageable safety profile for patients aged ≥65 years with relapsed or refractory large B-cell lymphoma (LBCL).

Major finding: At a median follow-up of 24.3 months, the median event-free survival was significantly longer with axi-cel vs standard of care (SOC; 21.5 vs 2.5 months; hazard ratio 0.276; descriptive P < .0001). The grade ≥3 treatment-emergent adverse event rates were 94% and 82% with axi-cel and SOC, respectively.

Study details: Findings are from a preplanned analysis of 109 patients aged ≥65 years with relapsed or refractory LBCL from the ZUMA-7 trial who were randomly assigned to receive second-line axi-cel (n = 51) or SOC (n = 58; 2-3 cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation).

Disclosures: This study was supported by Kite, a Gilead Company. Some authors reported ties with various organizations, including Kite and Gilead.

Source: Westin JR et al. Safety and efficacy of axicabtagene ciloleucel versus standard of care in patients 65 years of age or older with relapsed/refractory large B-cell lymphoma. Clin Cancer Res. 2023 (Mar 31). Doi: 10.1158/1078-0432.CCR-22-3136

Key clinical point: The addition of venetoclax to lenalidomide plus rituximab therapy may provide an effective and safe combination for the treatment of unselected patients with untreated mantle cell lymphoma (MCL).

Major finding: All patients were escalated to the maximum tolerated dose of venetoclax (400 mg daily). The overall response and complete remission rates were 96% and 86%, respectively. After a median follow-up of 27.5 months, the median overall survival and progression-free survival were not reached. No dose-limiting toxicity event was observed.

Study details: This multicenter phase 1 study included 28 unselected adult patients with untreated MCL who received induction therapy with lenalidomide (daily on days 1-21 of each cycle), rituximab (weekly during cycle 1 until cycle 2 day 1), and venetoclax (escalated weekly up to 400 mg daily) for 6-12 cycles followed by maintenance therapy.

Disclosures: This study was funded by AbbVie and the University of Michigan Rogel Cancer Center. Some authors reported ties with various organizations, including AbbVie.

Source: Phillips TJ et al. Adding venetoclax to lenalidomide and rituximab is safe and effective in patients with untreated mantle cell lymphoma. Blood Adv. 2023 (Apr 4). Doi: 10.1182/bloodadvances.2023009992

Key clinical point: The addition of venetoclax to lenalidomide plus rituximab therapy may provide an effective and safe combination for the treatment of unselected patients with untreated mantle cell lymphoma (MCL).

Major finding: All patients were escalated to the maximum tolerated dose of venetoclax (400 mg daily). The overall response and complete remission rates were 96% and 86%, respectively. After a median follow-up of 27.5 months, the median overall survival and progression-free survival were not reached. No dose-limiting toxicity event was observed.

Study details: This multicenter phase 1 study included 28 unselected adult patients with untreated MCL who received induction therapy with lenalidomide (daily on days 1-21 of each cycle), rituximab (weekly during cycle 1 until cycle 2 day 1), and venetoclax (escalated weekly up to 400 mg daily) for 6-12 cycles followed by maintenance therapy.

Disclosures: This study was funded by AbbVie and the University of Michigan Rogel Cancer Center. Some authors reported ties with various organizations, including AbbVie.

Source: Phillips TJ et al. Adding venetoclax to lenalidomide and rituximab is safe and effective in patients with untreated mantle cell lymphoma. Blood Adv. 2023 (Apr 4). Doi: 10.1182/bloodadvances.2023009992

Key clinical point: The addition of venetoclax to lenalidomide plus rituximab therapy may provide an effective and safe combination for the treatment of unselected patients with untreated mantle cell lymphoma (MCL).

Major finding: All patients were escalated to the maximum tolerated dose of venetoclax (400 mg daily). The overall response and complete remission rates were 96% and 86%, respectively. After a median follow-up of 27.5 months, the median overall survival and progression-free survival were not reached. No dose-limiting toxicity event was observed.

Study details: This multicenter phase 1 study included 28 unselected adult patients with untreated MCL who received induction therapy with lenalidomide (daily on days 1-21 of each cycle), rituximab (weekly during cycle 1 until cycle 2 day 1), and venetoclax (escalated weekly up to 400 mg daily) for 6-12 cycles followed by maintenance therapy.

Disclosures: This study was funded by AbbVie and the University of Michigan Rogel Cancer Center. Some authors reported ties with various organizations, including AbbVie.

Source: Phillips TJ et al. Adding venetoclax to lenalidomide and rituximab is safe and effective in patients with untreated mantle cell lymphoma. Blood Adv. 2023 (Apr 4). Doi: 10.1182/bloodadvances.2023009992