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36% of soldiers who attempt suicide have no mental health diagnosis
About one-third of enlisted soldiers who attempt suicide do not have a history of mental illness, say the authors of a retrospective longitudinal study among U.S. Army personnel.
However, health care use, exposure to violent crime, and first year of service all were significantly associated with suicide attempts.
The study, published online Aug. 29 in JAMA Psychiatry, analyzed administrative data from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) for 9,650 enlisted soldiers (74.8% male) who had a documented suicide attempt.
Overall, 36.3% of the soldiers studied who attempted suicide did not have a previous diagnosis of a mental health disorder. Having a history of mental illness was associated with sixfold higher odds of suicide attempt after adjusting for sociodemographic and service-related variables.
Among those without a history of mental health disorders, the first year of service was associated with sixfold higher odds of a suicide attempt (95% confidence interval, 4.7-7.7), and nearly 60% of those without a previous diagnosis who attempted suicide did so in their first year of service.
“This factor is noteworthy, because, as in the general population, most transitions from ideation to attempt among soldiers occur within 1 year of ideation onset,” wrote Robert J. Ursano, MD, professor of psychiatry and neurosciences at the Center for the Study of Traumatic Stress at the Uniformed Services University of the Health Sciences, Bethesda, Md., and his coauthors.
Among individuals without a history of mental health disorders, women had 2.6-fold higher odds (95% CI, 2.4-2.8) of a suicide attempt. The authors suggested that these
“Given the large proportion of first-year soldiers in the group without previous [mental health diagnosis], it is possible that women face additional stressors and challenges in the initial months of service,” they wrote.
Previous deployment was associated with 2.4-fold higher odds of suicide attempt; a 2-month delay in promotion was associated with 2.1-fold higher odds. In addition, a demotion in the past year was associated with 60% higher odds of a suicide attempt.
Health care use also showed associations with suicide attempts. Individuals who had visited outpatient services eight or more times in the past 2 months had more than threefold higher odds of suicide attempt. Those with an injury-related visit to outpatient services in the previous month had threefold higher odds, and those who had an injury-related visit to inpatient services had a 3.8-fold higher odds.
Exposure to minor violent crime and perpetration of major violent crime or family violence also were associated with higher odds of suicide attempt.
The authors cited several limitations. One is that the study did not capture unreported suicide attempts, mental disorders, or crimes.
The Army STARRS was supported by the Department of the Army, the U.S. Department of Health & Human Services, the National Institutes of Health, the National Institute of Mental Health and the Department of Defense. Two authors were employed by the NIMH, and two were Army liaisons or consultants.
SOURCE: Ursano RJ et al. JAMA Psychiatry. 2018 Aug 29. doi: 10.1001/jamapsychiatry.2018.2069.
An increase in suicide rates in the Army during the 2000s led to an increased focus on suicide prevention. However, at the time these study data were being collected, treatment for suicide ideation outside deployment largely occurred in the context of mental health clinics, wrote Mark A. Reger, PhD, Derek J. Smolenski, PhD, and Sarah P. Carter.
Therefore, individuals without mental health symptoms might have been less likely to be identified as being at risk, and therefore, less likely to receive evidence-based treatment. This suggests that greater focus is needed on suicide prevention in other settings, and particularly on combating the stigma associated with a mental health diagnosis – which is often around concerns of career effects from such a diagnosis.
To the Army’s credit, it has shifted toward integrating mental health services into new locations and services – including embedded behavioral health teams – with the aim of increasing access, decreasing stigma, and improving consultation with command.
Dr. Reger and Ms. Carter are affiliated with the Veterans Affairs Puget Sound Health Care System in Seattle, and Dr. Smolenski is with the Psychological Health Center of Excellence at the Defense Health Agency in Tacoma, Wash. These comments are taken from an accompanying editorial (JAMA Psychiatry. 2018 Aug 29. doi: 10.1001/jamapsychiatry.2018.2042). No conflicts of interest were declared.
An increase in suicide rates in the Army during the 2000s led to an increased focus on suicide prevention. However, at the time these study data were being collected, treatment for suicide ideation outside deployment largely occurred in the context of mental health clinics, wrote Mark A. Reger, PhD, Derek J. Smolenski, PhD, and Sarah P. Carter.
Therefore, individuals without mental health symptoms might have been less likely to be identified as being at risk, and therefore, less likely to receive evidence-based treatment. This suggests that greater focus is needed on suicide prevention in other settings, and particularly on combating the stigma associated with a mental health diagnosis – which is often around concerns of career effects from such a diagnosis.
To the Army’s credit, it has shifted toward integrating mental health services into new locations and services – including embedded behavioral health teams – with the aim of increasing access, decreasing stigma, and improving consultation with command.
Dr. Reger and Ms. Carter are affiliated with the Veterans Affairs Puget Sound Health Care System in Seattle, and Dr. Smolenski is with the Psychological Health Center of Excellence at the Defense Health Agency in Tacoma, Wash. These comments are taken from an accompanying editorial (JAMA Psychiatry. 2018 Aug 29. doi: 10.1001/jamapsychiatry.2018.2042). No conflicts of interest were declared.
An increase in suicide rates in the Army during the 2000s led to an increased focus on suicide prevention. However, at the time these study data were being collected, treatment for suicide ideation outside deployment largely occurred in the context of mental health clinics, wrote Mark A. Reger, PhD, Derek J. Smolenski, PhD, and Sarah P. Carter.
Therefore, individuals without mental health symptoms might have been less likely to be identified as being at risk, and therefore, less likely to receive evidence-based treatment. This suggests that greater focus is needed on suicide prevention in other settings, and particularly on combating the stigma associated with a mental health diagnosis – which is often around concerns of career effects from such a diagnosis.
To the Army’s credit, it has shifted toward integrating mental health services into new locations and services – including embedded behavioral health teams – with the aim of increasing access, decreasing stigma, and improving consultation with command.
Dr. Reger and Ms. Carter are affiliated with the Veterans Affairs Puget Sound Health Care System in Seattle, and Dr. Smolenski is with the Psychological Health Center of Excellence at the Defense Health Agency in Tacoma, Wash. These comments are taken from an accompanying editorial (JAMA Psychiatry. 2018 Aug 29. doi: 10.1001/jamapsychiatry.2018.2042). No conflicts of interest were declared.
About one-third of enlisted soldiers who attempt suicide do not have a history of mental illness, say the authors of a retrospective longitudinal study among U.S. Army personnel.
However, health care use, exposure to violent crime, and first year of service all were significantly associated with suicide attempts.
The study, published online Aug. 29 in JAMA Psychiatry, analyzed administrative data from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) for 9,650 enlisted soldiers (74.8% male) who had a documented suicide attempt.
Overall, 36.3% of the soldiers studied who attempted suicide did not have a previous diagnosis of a mental health disorder. Having a history of mental illness was associated with sixfold higher odds of suicide attempt after adjusting for sociodemographic and service-related variables.
Among those without a history of mental health disorders, the first year of service was associated with sixfold higher odds of a suicide attempt (95% confidence interval, 4.7-7.7), and nearly 60% of those without a previous diagnosis who attempted suicide did so in their first year of service.
“This factor is noteworthy, because, as in the general population, most transitions from ideation to attempt among soldiers occur within 1 year of ideation onset,” wrote Robert J. Ursano, MD, professor of psychiatry and neurosciences at the Center for the Study of Traumatic Stress at the Uniformed Services University of the Health Sciences, Bethesda, Md., and his coauthors.
Among individuals without a history of mental health disorders, women had 2.6-fold higher odds (95% CI, 2.4-2.8) of a suicide attempt. The authors suggested that these
“Given the large proportion of first-year soldiers in the group without previous [mental health diagnosis], it is possible that women face additional stressors and challenges in the initial months of service,” they wrote.
Previous deployment was associated with 2.4-fold higher odds of suicide attempt; a 2-month delay in promotion was associated with 2.1-fold higher odds. In addition, a demotion in the past year was associated with 60% higher odds of a suicide attempt.
Health care use also showed associations with suicide attempts. Individuals who had visited outpatient services eight or more times in the past 2 months had more than threefold higher odds of suicide attempt. Those with an injury-related visit to outpatient services in the previous month had threefold higher odds, and those who had an injury-related visit to inpatient services had a 3.8-fold higher odds.
Exposure to minor violent crime and perpetration of major violent crime or family violence also were associated with higher odds of suicide attempt.
The authors cited several limitations. One is that the study did not capture unreported suicide attempts, mental disorders, or crimes.
The Army STARRS was supported by the Department of the Army, the U.S. Department of Health & Human Services, the National Institutes of Health, the National Institute of Mental Health and the Department of Defense. Two authors were employed by the NIMH, and two were Army liaisons or consultants.
SOURCE: Ursano RJ et al. JAMA Psychiatry. 2018 Aug 29. doi: 10.1001/jamapsychiatry.2018.2069.
About one-third of enlisted soldiers who attempt suicide do not have a history of mental illness, say the authors of a retrospective longitudinal study among U.S. Army personnel.
However, health care use, exposure to violent crime, and first year of service all were significantly associated with suicide attempts.
The study, published online Aug. 29 in JAMA Psychiatry, analyzed administrative data from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) for 9,650 enlisted soldiers (74.8% male) who had a documented suicide attempt.
Overall, 36.3% of the soldiers studied who attempted suicide did not have a previous diagnosis of a mental health disorder. Having a history of mental illness was associated with sixfold higher odds of suicide attempt after adjusting for sociodemographic and service-related variables.
Among those without a history of mental health disorders, the first year of service was associated with sixfold higher odds of a suicide attempt (95% confidence interval, 4.7-7.7), and nearly 60% of those without a previous diagnosis who attempted suicide did so in their first year of service.
“This factor is noteworthy, because, as in the general population, most transitions from ideation to attempt among soldiers occur within 1 year of ideation onset,” wrote Robert J. Ursano, MD, professor of psychiatry and neurosciences at the Center for the Study of Traumatic Stress at the Uniformed Services University of the Health Sciences, Bethesda, Md., and his coauthors.
Among individuals without a history of mental health disorders, women had 2.6-fold higher odds (95% CI, 2.4-2.8) of a suicide attempt. The authors suggested that these
“Given the large proportion of first-year soldiers in the group without previous [mental health diagnosis], it is possible that women face additional stressors and challenges in the initial months of service,” they wrote.
Previous deployment was associated with 2.4-fold higher odds of suicide attempt; a 2-month delay in promotion was associated with 2.1-fold higher odds. In addition, a demotion in the past year was associated with 60% higher odds of a suicide attempt.
Health care use also showed associations with suicide attempts. Individuals who had visited outpatient services eight or more times in the past 2 months had more than threefold higher odds of suicide attempt. Those with an injury-related visit to outpatient services in the previous month had threefold higher odds, and those who had an injury-related visit to inpatient services had a 3.8-fold higher odds.
Exposure to minor violent crime and perpetration of major violent crime or family violence also were associated with higher odds of suicide attempt.
The authors cited several limitations. One is that the study did not capture unreported suicide attempts, mental disorders, or crimes.
The Army STARRS was supported by the Department of the Army, the U.S. Department of Health & Human Services, the National Institutes of Health, the National Institute of Mental Health and the Department of Defense. Two authors were employed by the NIMH, and two were Army liaisons or consultants.
SOURCE: Ursano RJ et al. JAMA Psychiatry. 2018 Aug 29. doi: 10.1001/jamapsychiatry.2018.2069.
FROM JAMA PSYCHIATRY
Key clinical point: Many U.S. Army soldiers who attempt suicide and have no mental health diagnosis probably have undetected mental health disorders.
Major finding: More than one-third of soldiers who have attempted suicide do not have a history of mental health diagnosis.
Study details: Retrospective cohort study in 9,650 enlisted soldiers who had a documented suicide attempt.
Disclosures: The Army STARRS was supported by the Department of the Army, the U.S. Department of Health & Human Services, the National Institutes of Health, the National Institute of Mental Health, and the Department of Defense. Two authors were employed by the NIMH, and two were Army liaisons or consultants.
Source: Ursano RJ et al. JAMA Psychiatry. 2018 Aug 29. doi: 10.1001/jamapsychiatry.2018.2069.
Declining lung function linked to heart failure, stroke
Rapid declines in spirometric measures of lung function were associated with higher risks of cardiovascular disease, according to a recent analysis of a large, prospective cohort study.
Rapid declines in forced expiratory volume in 1 second (FEV1) were associated with increased incidence of heart failure, stroke, and death in the analysis of the ARIC (Atherosclerosis Risk in Communities) study.
The risk of incident heart failure among FEV1 rapid decliners was particularly high, with a fourfold increase within 12 months. That suggests clinicians should carefully consider incipient heart failure in patients with rapid changes in FEV1, investigators reported in the Journal of the American College of Cardiology.
Rapid declines in forced vital capacity (FVC) were also associated with higher incidences of heart failure and death in the analysis by Odilson M. Silvestre, MD, of the division of cardiovascular medicine at Brigham and Women’s Hospital, Boston, and colleagues.
The analysis included a total of 10,351 ARIC participants with a mean follow-up of 17 years. All had undergone spirometry at the first study visit between 1987 and 1989, and on the second visit between 1990 and 1992.
One-quarter of participants were classified as FEV1 rapid decliners, defined by an FEV1 decrease of at least 1.9% per year. Likewise, one-quarter of participants were classified as FVC rapid decliners, based on an FVC decrease of at least 2.1%.
Rapid decline in FEV1 was associated with a higher risk of incident heart failure (hazard ratio, 1.17; 95% confidence interval, 1.04-1.33; P = .010), and was most prognostic in the first year of follow-up (HR, 4.22; 95% CI, 1.34-13.26; P = .01), investigators said.
Rapid decline in FVC was likewise associated with a greater heart failure risk (HR, 1.27; 95% CI, 1.12-1.44; P less than .001).
Increased heart failure risk persisted after excluding patients with incident coronary heart disease in both the FEV1 and FVC rapid decliners, the investigators said.
A rapid decline in FEV1 was also associated with a higher stroke risk (HR, 1.25; 95% CI, 1.04-1.50; P = .015).
FEV1 rapid decliners had a higher overall rate of incident cardiovascular disease than those without rapid decline, even after adjustment for baseline variables such as age, sex, race, body mass index, and heart rate (HR, 1.15; 95% CI, 1.04-1.26; P = .004), and FVC rapid decliners likewise had a 19% greater risk of the composite endpoint (HR, 1.19; 95% CI, 1.08-1.32; P less than .001).
The National Heart, Lung, and Blood Institute, the American Heart Association, and other sources supported the study. Dr. Silvestre reported having no relevant conflicts.
SOURCE: Silvestre OM et al. J Am Coll Cardiol. 2018 Sep 4;72(10):1109-22.
Cardiologists and pulmonologists should closely collaborate to better identify the relationship between lung function decline and early cardiovascular disease detection, said the authors of an editorial accompanying the study.
Improved collaboration would help manage these conditions, stopping early disease progression and preventing overt cardiovascular disease, wrote Daniel A. Duprez, MD, PhD, and David R. Jacobs Jr., PhD.
“The resulting symptomatic and prognostic benefits outweigh those attainable by treating either condition alone,” noted Dr. Duprez and Dr. Jacobs.
The study by Dr. Silvestre and coauthors showed that rapid declines in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) among participants in the ARIC (Atherosclerosis Risk in Communities) study were associated with a higher incidence of composite cardiovascular disease, heart failure, and total death.
The association between FEV1 and new heart failure was substantially impacted by 22 heart failure events occurring in the first year, with a hazard ratio of 4.22 for predicting those cases, the editorial authors noted.
“We suggest that this association with early cases could be the result of reversed causality, reflecting heart failure undiagnosed at the second spirometry test,” they explained (J Am Coll Cardiol. 2018 Sep 4;72[10]:1123-5).
Dr. Duprez is with the cardiovascular division of the University of Minnesota, Minneapolis, and Dr. Jacobs is with the division of epidemiology and community health at the University of Minnesota, Minneapolis. Dr. Duprez and Dr. Jacobs reported they had no relevant disclosures.
Cardiologists and pulmonologists should closely collaborate to better identify the relationship between lung function decline and early cardiovascular disease detection, said the authors of an editorial accompanying the study.
Improved collaboration would help manage these conditions, stopping early disease progression and preventing overt cardiovascular disease, wrote Daniel A. Duprez, MD, PhD, and David R. Jacobs Jr., PhD.
“The resulting symptomatic and prognostic benefits outweigh those attainable by treating either condition alone,” noted Dr. Duprez and Dr. Jacobs.
The study by Dr. Silvestre and coauthors showed that rapid declines in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) among participants in the ARIC (Atherosclerosis Risk in Communities) study were associated with a higher incidence of composite cardiovascular disease, heart failure, and total death.
The association between FEV1 and new heart failure was substantially impacted by 22 heart failure events occurring in the first year, with a hazard ratio of 4.22 for predicting those cases, the editorial authors noted.
“We suggest that this association with early cases could be the result of reversed causality, reflecting heart failure undiagnosed at the second spirometry test,” they explained (J Am Coll Cardiol. 2018 Sep 4;72[10]:1123-5).
Dr. Duprez is with the cardiovascular division of the University of Minnesota, Minneapolis, and Dr. Jacobs is with the division of epidemiology and community health at the University of Minnesota, Minneapolis. Dr. Duprez and Dr. Jacobs reported they had no relevant disclosures.
Cardiologists and pulmonologists should closely collaborate to better identify the relationship between lung function decline and early cardiovascular disease detection, said the authors of an editorial accompanying the study.
Improved collaboration would help manage these conditions, stopping early disease progression and preventing overt cardiovascular disease, wrote Daniel A. Duprez, MD, PhD, and David R. Jacobs Jr., PhD.
“The resulting symptomatic and prognostic benefits outweigh those attainable by treating either condition alone,” noted Dr. Duprez and Dr. Jacobs.
The study by Dr. Silvestre and coauthors showed that rapid declines in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) among participants in the ARIC (Atherosclerosis Risk in Communities) study were associated with a higher incidence of composite cardiovascular disease, heart failure, and total death.
The association between FEV1 and new heart failure was substantially impacted by 22 heart failure events occurring in the first year, with a hazard ratio of 4.22 for predicting those cases, the editorial authors noted.
“We suggest that this association with early cases could be the result of reversed causality, reflecting heart failure undiagnosed at the second spirometry test,” they explained (J Am Coll Cardiol. 2018 Sep 4;72[10]:1123-5).
Dr. Duprez is with the cardiovascular division of the University of Minnesota, Minneapolis, and Dr. Jacobs is with the division of epidemiology and community health at the University of Minnesota, Minneapolis. Dr. Duprez and Dr. Jacobs reported they had no relevant disclosures.
Rapid declines in spirometric measures of lung function were associated with higher risks of cardiovascular disease, according to a recent analysis of a large, prospective cohort study.
Rapid declines in forced expiratory volume in 1 second (FEV1) were associated with increased incidence of heart failure, stroke, and death in the analysis of the ARIC (Atherosclerosis Risk in Communities) study.
The risk of incident heart failure among FEV1 rapid decliners was particularly high, with a fourfold increase within 12 months. That suggests clinicians should carefully consider incipient heart failure in patients with rapid changes in FEV1, investigators reported in the Journal of the American College of Cardiology.
Rapid declines in forced vital capacity (FVC) were also associated with higher incidences of heart failure and death in the analysis by Odilson M. Silvestre, MD, of the division of cardiovascular medicine at Brigham and Women’s Hospital, Boston, and colleagues.
The analysis included a total of 10,351 ARIC participants with a mean follow-up of 17 years. All had undergone spirometry at the first study visit between 1987 and 1989, and on the second visit between 1990 and 1992.
One-quarter of participants were classified as FEV1 rapid decliners, defined by an FEV1 decrease of at least 1.9% per year. Likewise, one-quarter of participants were classified as FVC rapid decliners, based on an FVC decrease of at least 2.1%.
Rapid decline in FEV1 was associated with a higher risk of incident heart failure (hazard ratio, 1.17; 95% confidence interval, 1.04-1.33; P = .010), and was most prognostic in the first year of follow-up (HR, 4.22; 95% CI, 1.34-13.26; P = .01), investigators said.
Rapid decline in FVC was likewise associated with a greater heart failure risk (HR, 1.27; 95% CI, 1.12-1.44; P less than .001).
Increased heart failure risk persisted after excluding patients with incident coronary heart disease in both the FEV1 and FVC rapid decliners, the investigators said.
A rapid decline in FEV1 was also associated with a higher stroke risk (HR, 1.25; 95% CI, 1.04-1.50; P = .015).
FEV1 rapid decliners had a higher overall rate of incident cardiovascular disease than those without rapid decline, even after adjustment for baseline variables such as age, sex, race, body mass index, and heart rate (HR, 1.15; 95% CI, 1.04-1.26; P = .004), and FVC rapid decliners likewise had a 19% greater risk of the composite endpoint (HR, 1.19; 95% CI, 1.08-1.32; P less than .001).
The National Heart, Lung, and Blood Institute, the American Heart Association, and other sources supported the study. Dr. Silvestre reported having no relevant conflicts.
SOURCE: Silvestre OM et al. J Am Coll Cardiol. 2018 Sep 4;72(10):1109-22.
Rapid declines in spirometric measures of lung function were associated with higher risks of cardiovascular disease, according to a recent analysis of a large, prospective cohort study.
Rapid declines in forced expiratory volume in 1 second (FEV1) were associated with increased incidence of heart failure, stroke, and death in the analysis of the ARIC (Atherosclerosis Risk in Communities) study.
The risk of incident heart failure among FEV1 rapid decliners was particularly high, with a fourfold increase within 12 months. That suggests clinicians should carefully consider incipient heart failure in patients with rapid changes in FEV1, investigators reported in the Journal of the American College of Cardiology.
Rapid declines in forced vital capacity (FVC) were also associated with higher incidences of heart failure and death in the analysis by Odilson M. Silvestre, MD, of the division of cardiovascular medicine at Brigham and Women’s Hospital, Boston, and colleagues.
The analysis included a total of 10,351 ARIC participants with a mean follow-up of 17 years. All had undergone spirometry at the first study visit between 1987 and 1989, and on the second visit between 1990 and 1992.
One-quarter of participants were classified as FEV1 rapid decliners, defined by an FEV1 decrease of at least 1.9% per year. Likewise, one-quarter of participants were classified as FVC rapid decliners, based on an FVC decrease of at least 2.1%.
Rapid decline in FEV1 was associated with a higher risk of incident heart failure (hazard ratio, 1.17; 95% confidence interval, 1.04-1.33; P = .010), and was most prognostic in the first year of follow-up (HR, 4.22; 95% CI, 1.34-13.26; P = .01), investigators said.
Rapid decline in FVC was likewise associated with a greater heart failure risk (HR, 1.27; 95% CI, 1.12-1.44; P less than .001).
Increased heart failure risk persisted after excluding patients with incident coronary heart disease in both the FEV1 and FVC rapid decliners, the investigators said.
A rapid decline in FEV1 was also associated with a higher stroke risk (HR, 1.25; 95% CI, 1.04-1.50; P = .015).
FEV1 rapid decliners had a higher overall rate of incident cardiovascular disease than those without rapid decline, even after adjustment for baseline variables such as age, sex, race, body mass index, and heart rate (HR, 1.15; 95% CI, 1.04-1.26; P = .004), and FVC rapid decliners likewise had a 19% greater risk of the composite endpoint (HR, 1.19; 95% CI, 1.08-1.32; P less than .001).
The National Heart, Lung, and Blood Institute, the American Heart Association, and other sources supported the study. Dr. Silvestre reported having no relevant conflicts.
SOURCE: Silvestre OM et al. J Am Coll Cardiol. 2018 Sep 4;72(10):1109-22.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point: Rapid declines in spirometric measures of lung function were associated with higher risks of heart failure, among other adverse cardiovascular outcomes.
Major finding: Rapid decline in forced expiratory volume in 1 second was associated with higher risk of incident heart failure (HR, 1.17; 95% CI, 1.04-1.33; P = .010), and was most prognostic in the first year of follow-up (HR, 4.22; 95% CI, 1.34-13.26; P = .01).
Study details: An analysis including a total of 10,351 participants in a large, prospective cohort study with a mean follow-up of 17 years.
Disclosures: The National Heart, Lung, and Blood Institute, the American Heart Association, and other sources supported the study. Dr. Silvestre reported having no relevant conflicts.
Source: Silvestre OM et al. J Am Coll Cardiol. 2018 Sep 4;72(10):1109-22.
European Commission approves first CAR T-cell therapies
The , two chimeric antigen receptor (CAR) T-cell therapies.
Tisagenlecleucel is now approved for use in pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post transplant, or in second or later relapse.
Tisagenlecleucel is also approved to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.
Axicabtagene ciloleucel is approved for adults with relapsed/refractory DLBCL and primary mediastinal large B-cell lymphoma (PMBCL) after two or more lines of systemic therapy. The treatment is marketed by Kite, a Gilead company.
The axicabtagene ciloleucel approval is based on results from the single arm, ZUMA-1 trial. During the study of 101 patients who received a single infusion, 72% responded to therapy and 51% achieved a complete response. At 1 year, median overall survival had not been reached.
Novartis expects to launch tisagenlecleucel initially for pediatric ALL. The company said timing for tisagenlecleucel availability in each country will depend on multiple factors, including the onboarding of qualified treatment centers for the appropriate indications, as well as the completion of national reimbursement procedures.
The EC’s approval of tisagenlecleucel is based on results from the phase 2 JULIET and ELIANA trials.
Updated results from JULIET were presented at the annual congress of the European Hematology Association in June 2018. The trial enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Most of the patients who discontinued before dosing did so because of disease progression or clinical deterioration.
The median time from infusion to data cutoff was 13.9 months.
The overall response rate was 52%, and the complete response (CR) rate was 40%. At the time of data cutoff, none of the responders had gone on to receive a stem cell transplant.
Updated results from ELIANA were published in New England Journal of Medicine (2018;378:439-48).
The trial included 75 children and young adults with relapsed/refractory ALL. The overall remission rate was 81% (61/75), with 60% of patients (n = 45) achieving a complete remission (CR) and 21% (n = 16) achieving a CR with incomplete hematologic recovery (CRi).
All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.
The , two chimeric antigen receptor (CAR) T-cell therapies.
Tisagenlecleucel is now approved for use in pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post transplant, or in second or later relapse.
Tisagenlecleucel is also approved to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.
Axicabtagene ciloleucel is approved for adults with relapsed/refractory DLBCL and primary mediastinal large B-cell lymphoma (PMBCL) after two or more lines of systemic therapy. The treatment is marketed by Kite, a Gilead company.
The axicabtagene ciloleucel approval is based on results from the single arm, ZUMA-1 trial. During the study of 101 patients who received a single infusion, 72% responded to therapy and 51% achieved a complete response. At 1 year, median overall survival had not been reached.
Novartis expects to launch tisagenlecleucel initially for pediatric ALL. The company said timing for tisagenlecleucel availability in each country will depend on multiple factors, including the onboarding of qualified treatment centers for the appropriate indications, as well as the completion of national reimbursement procedures.
The EC’s approval of tisagenlecleucel is based on results from the phase 2 JULIET and ELIANA trials.
Updated results from JULIET were presented at the annual congress of the European Hematology Association in June 2018. The trial enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Most of the patients who discontinued before dosing did so because of disease progression or clinical deterioration.
The median time from infusion to data cutoff was 13.9 months.
The overall response rate was 52%, and the complete response (CR) rate was 40%. At the time of data cutoff, none of the responders had gone on to receive a stem cell transplant.
Updated results from ELIANA were published in New England Journal of Medicine (2018;378:439-48).
The trial included 75 children and young adults with relapsed/refractory ALL. The overall remission rate was 81% (61/75), with 60% of patients (n = 45) achieving a complete remission (CR) and 21% (n = 16) achieving a CR with incomplete hematologic recovery (CRi).
All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.
The , two chimeric antigen receptor (CAR) T-cell therapies.
Tisagenlecleucel is now approved for use in pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post transplant, or in second or later relapse.
Tisagenlecleucel is also approved to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have received two or more lines of systemic therapy.
Axicabtagene ciloleucel is approved for adults with relapsed/refractory DLBCL and primary mediastinal large B-cell lymphoma (PMBCL) after two or more lines of systemic therapy. The treatment is marketed by Kite, a Gilead company.
The axicabtagene ciloleucel approval is based on results from the single arm, ZUMA-1 trial. During the study of 101 patients who received a single infusion, 72% responded to therapy and 51% achieved a complete response. At 1 year, median overall survival had not been reached.
Novartis expects to launch tisagenlecleucel initially for pediatric ALL. The company said timing for tisagenlecleucel availability in each country will depend on multiple factors, including the onboarding of qualified treatment centers for the appropriate indications, as well as the completion of national reimbursement procedures.
The EC’s approval of tisagenlecleucel is based on results from the phase 2 JULIET and ELIANA trials.
Updated results from JULIET were presented at the annual congress of the European Hematology Association in June 2018. The trial enrolled 165 adults with relapsed/refractory DLBCL, and 111 of them received a single infusion of tisagenlecleucel. Most of the patients who discontinued before dosing did so because of disease progression or clinical deterioration.
The median time from infusion to data cutoff was 13.9 months.
The overall response rate was 52%, and the complete response (CR) rate was 40%. At the time of data cutoff, none of the responders had gone on to receive a stem cell transplant.
Updated results from ELIANA were published in New England Journal of Medicine (2018;378:439-48).
The trial included 75 children and young adults with relapsed/refractory ALL. The overall remission rate was 81% (61/75), with 60% of patients (n = 45) achieving a complete remission (CR) and 21% (n = 16) achieving a CR with incomplete hematologic recovery (CRi).
All patients whose best response was CR/CRi were negative for minimal residual disease. The median duration of response was not met.
HIV, HBV, and HCV Increase Risks After Joint Replacement
As patients with HIV, hepatitis B (HBV), and hepatitis C (HCV) live longer, more active lives with the help of antiviral treatments, they are now more often having joint replacement surgeries. But HIV, HBV, and HCV can increase the risk of postoperative complications, say researchers from Duke University in North Carolina.
The researchers studied 16,338 patients in 4 cohorts: those with HIV, HBV, HCV, and HIV plus HBV or HCV. They evaluated the patients at 30 days, 90 days, and 2 years after total joint arthroplasty (TJA), comparing their progress with that of a control group.
Patients with HBV and HCV were at risk of both acute and long-term medical and surgical complications. At 90 days and 2 years, the participants had increased risk of pneumonia, sepsis, joint infection, and revision surgery. They also had a greater risk of complications than did patients with HIV, especially for infection, within the first 90 days postsurgery.
Notably, after TJA, patients with HCV had increased risk of acute kidney injury, sepsis, and transfusion at 30 and 90 days. After hip replacement, patients with HBV had a higher risk of acute kidney injury, pneumonia, and transfusion at 30 and 90 days.
Only 364 patients in the study had both HIV and HBV or HBC, but they did have a greater risk of transfusion at 30 and 90 days following both knee and hip surgery.
Following total hip arthroplasty, patients with HIV were more at risk for deep vein thrombosis and transfusion rather than infection. The lower incidence of infection is likely to be related to effective highly active antiretroviral therapy, the researchers say. HIV patients also were more likely to have mechanical complications, such as loosening, periprosthetic fracture, and revision at 90 days, but not at 2 years. Patients with HIV who underwent total knee arthroplasty (TKA) had a higher risk of death at 30 days and medical complications at 90 days. At 2 years, they had a higher risk of periprosthetic joint infection, irrigation and debridement, and revision. The researchers say the higher incidence of mechanical complications can be explained by the younger, more active, and healthy HIV patients in the cohort—the majority were aged younger than 65 years. They also emphasize that the only risk of infection following TJA in their study was 2 years after TKA.
The researchers suggest that their findings could help prompt future guidelines supporting routine screening prior to elective TJA.
Source:
Kildow BJ, Politzer CS, DiLallo M, Bolognesi MP, Seyler TM. J Arthroplasty. 2018;33(suppl 7):S86-S92.
doi: 10.1016/j.arth.2017.10.061.
As patients with HIV, hepatitis B (HBV), and hepatitis C (HCV) live longer, more active lives with the help of antiviral treatments, they are now more often having joint replacement surgeries. But HIV, HBV, and HCV can increase the risk of postoperative complications, say researchers from Duke University in North Carolina.
The researchers studied 16,338 patients in 4 cohorts: those with HIV, HBV, HCV, and HIV plus HBV or HCV. They evaluated the patients at 30 days, 90 days, and 2 years after total joint arthroplasty (TJA), comparing their progress with that of a control group.
Patients with HBV and HCV were at risk of both acute and long-term medical and surgical complications. At 90 days and 2 years, the participants had increased risk of pneumonia, sepsis, joint infection, and revision surgery. They also had a greater risk of complications than did patients with HIV, especially for infection, within the first 90 days postsurgery.
Notably, after TJA, patients with HCV had increased risk of acute kidney injury, sepsis, and transfusion at 30 and 90 days. After hip replacement, patients with HBV had a higher risk of acute kidney injury, pneumonia, and transfusion at 30 and 90 days.
Only 364 patients in the study had both HIV and HBV or HBC, but they did have a greater risk of transfusion at 30 and 90 days following both knee and hip surgery.
Following total hip arthroplasty, patients with HIV were more at risk for deep vein thrombosis and transfusion rather than infection. The lower incidence of infection is likely to be related to effective highly active antiretroviral therapy, the researchers say. HIV patients also were more likely to have mechanical complications, such as loosening, periprosthetic fracture, and revision at 90 days, but not at 2 years. Patients with HIV who underwent total knee arthroplasty (TKA) had a higher risk of death at 30 days and medical complications at 90 days. At 2 years, they had a higher risk of periprosthetic joint infection, irrigation and debridement, and revision. The researchers say the higher incidence of mechanical complications can be explained by the younger, more active, and healthy HIV patients in the cohort—the majority were aged younger than 65 years. They also emphasize that the only risk of infection following TJA in their study was 2 years after TKA.
The researchers suggest that their findings could help prompt future guidelines supporting routine screening prior to elective TJA.
Source:
Kildow BJ, Politzer CS, DiLallo M, Bolognesi MP, Seyler TM. J Arthroplasty. 2018;33(suppl 7):S86-S92.
doi: 10.1016/j.arth.2017.10.061.
As patients with HIV, hepatitis B (HBV), and hepatitis C (HCV) live longer, more active lives with the help of antiviral treatments, they are now more often having joint replacement surgeries. But HIV, HBV, and HCV can increase the risk of postoperative complications, say researchers from Duke University in North Carolina.
The researchers studied 16,338 patients in 4 cohorts: those with HIV, HBV, HCV, and HIV plus HBV or HCV. They evaluated the patients at 30 days, 90 days, and 2 years after total joint arthroplasty (TJA), comparing their progress with that of a control group.
Patients with HBV and HCV were at risk of both acute and long-term medical and surgical complications. At 90 days and 2 years, the participants had increased risk of pneumonia, sepsis, joint infection, and revision surgery. They also had a greater risk of complications than did patients with HIV, especially for infection, within the first 90 days postsurgery.
Notably, after TJA, patients with HCV had increased risk of acute kidney injury, sepsis, and transfusion at 30 and 90 days. After hip replacement, patients with HBV had a higher risk of acute kidney injury, pneumonia, and transfusion at 30 and 90 days.
Only 364 patients in the study had both HIV and HBV or HBC, but they did have a greater risk of transfusion at 30 and 90 days following both knee and hip surgery.
Following total hip arthroplasty, patients with HIV were more at risk for deep vein thrombosis and transfusion rather than infection. The lower incidence of infection is likely to be related to effective highly active antiretroviral therapy, the researchers say. HIV patients also were more likely to have mechanical complications, such as loosening, periprosthetic fracture, and revision at 90 days, but not at 2 years. Patients with HIV who underwent total knee arthroplasty (TKA) had a higher risk of death at 30 days and medical complications at 90 days. At 2 years, they had a higher risk of periprosthetic joint infection, irrigation and debridement, and revision. The researchers say the higher incidence of mechanical complications can be explained by the younger, more active, and healthy HIV patients in the cohort—the majority were aged younger than 65 years. They also emphasize that the only risk of infection following TJA in their study was 2 years after TKA.
The researchers suggest that their findings could help prompt future guidelines supporting routine screening prior to elective TJA.
Source:
Kildow BJ, Politzer CS, DiLallo M, Bolognesi MP, Seyler TM. J Arthroplasty. 2018;33(suppl 7):S86-S92.
doi: 10.1016/j.arth.2017.10.061.
ctDNA predicts early outcomes in DLBCL
Measurement of circulating tumor DNA (ctDNA) could be a new and useful tool for predicting survival outcomes and response to therapy in patients with diffuse large B-cell lymphoma (DLBCL), according to authors of a recent prospective study.
Pretreatment ctDNA levels predicted 24-month event-free survival – an important disease milestone in DLBCL – as well as overall survival in the study, which included more than 200 patients at six institutions in North America and Europe.
Changes in ctDNA during treatment were prognostic for outcomes as early as 21 days into therapy, according to corresponding author Ash A. Alizadeh, MD, PhD, of Stanford (Calif.) University and his coinvestigators.
“Our data suggest that both pretreatment and dynamic assessments of ctDNA are feasible and can add to established risk factors,” Dr. Alizadeh and his coauthors reported in the Journal of Clinical Oncology.
ctDNA was detected in 98% of the 217 patients evaluated, which demonstrated the “potentially universal applicability” of this approach, they wrote in the report.
In an evaluation of pretreatment ctDNA levels, investigators found a 2.5 log haploid genome equivalents per milliliter (hGE/mL) threshold stratified patient outcomes. Event-free survival was significantly inferior at 24 months in patients with ctDNA above that threshold, with hazard ratios of 2.6 (P = .007) for frontline treatment and 2.9 (P = 0.01) for salvage.
On-treatment ctDNA levels were favorably prognostic for outcomes in patients receiving frontline therapy, according to investigators. An early molecular response (EMR), defined as a 2-log decrease in ctDNA levels after one cycle of treatment, was associated with a 24-month event-free survival of 83% versus 50% for no EMR (P = .0015).
Major molecular response (MMR), defined as a 2.5-log drop in ctDNA after two cycles of treatment, was associated with a 24-month event-free survival of 82% versus 46% for no MMR in patients on frontline therapy (P less than .001).
In one cohort of patients receiving salvage therapy, EMR also predicted superior 24-month event-free survival, according to investigators.
The EMR measure was also favorably prognostic for overall survival in both the frontline and salvage settings.
The prognostic value of measuring ctDNA was independent of International Prognostic Index (IPI) and interim PET/CT studies, results of multivariable analysis showed.
Patients had “excellent outcomes” if they had both molecular response and favorable interim PET results, and conversely, patients were at “extremely high risk” for treatment failure if they had no molecular response and a positive PET scan.
“The identification of patients at exceptionally high risk (i.e., interim PET/CT positive and not achieving EMR/MMR) could provide an opportunity for early intervention with alternative treatments, including autologous bone marrow transplantation or chimeric antigen receptor T cells,” the researchers wrote.
Patients in the study were all treated with combination immunochemotherapy according to local standards.
Dr. Alizadeh reported disclosures related to CiberMed, Forty Seven, Janssen Oncology, Celgene, Roche/Genentech, and Gilead, as well as patent filings on ctDNA detection assigned to Stanford University.
SOURCE: Kurtz DM et al. J Clin Oncol. 2018 Aug 20. doi: 10.1200/JCO.2018.78.5246.
Measurement of circulating tumor DNA (ctDNA) could be a new and useful tool for predicting survival outcomes and response to therapy in patients with diffuse large B-cell lymphoma (DLBCL), according to authors of a recent prospective study.
Pretreatment ctDNA levels predicted 24-month event-free survival – an important disease milestone in DLBCL – as well as overall survival in the study, which included more than 200 patients at six institutions in North America and Europe.
Changes in ctDNA during treatment were prognostic for outcomes as early as 21 days into therapy, according to corresponding author Ash A. Alizadeh, MD, PhD, of Stanford (Calif.) University and his coinvestigators.
“Our data suggest that both pretreatment and dynamic assessments of ctDNA are feasible and can add to established risk factors,” Dr. Alizadeh and his coauthors reported in the Journal of Clinical Oncology.
ctDNA was detected in 98% of the 217 patients evaluated, which demonstrated the “potentially universal applicability” of this approach, they wrote in the report.
In an evaluation of pretreatment ctDNA levels, investigators found a 2.5 log haploid genome equivalents per milliliter (hGE/mL) threshold stratified patient outcomes. Event-free survival was significantly inferior at 24 months in patients with ctDNA above that threshold, with hazard ratios of 2.6 (P = .007) for frontline treatment and 2.9 (P = 0.01) for salvage.
On-treatment ctDNA levels were favorably prognostic for outcomes in patients receiving frontline therapy, according to investigators. An early molecular response (EMR), defined as a 2-log decrease in ctDNA levels after one cycle of treatment, was associated with a 24-month event-free survival of 83% versus 50% for no EMR (P = .0015).
Major molecular response (MMR), defined as a 2.5-log drop in ctDNA after two cycles of treatment, was associated with a 24-month event-free survival of 82% versus 46% for no MMR in patients on frontline therapy (P less than .001).
In one cohort of patients receiving salvage therapy, EMR also predicted superior 24-month event-free survival, according to investigators.
The EMR measure was also favorably prognostic for overall survival in both the frontline and salvage settings.
The prognostic value of measuring ctDNA was independent of International Prognostic Index (IPI) and interim PET/CT studies, results of multivariable analysis showed.
Patients had “excellent outcomes” if they had both molecular response and favorable interim PET results, and conversely, patients were at “extremely high risk” for treatment failure if they had no molecular response and a positive PET scan.
“The identification of patients at exceptionally high risk (i.e., interim PET/CT positive and not achieving EMR/MMR) could provide an opportunity for early intervention with alternative treatments, including autologous bone marrow transplantation or chimeric antigen receptor T cells,” the researchers wrote.
Patients in the study were all treated with combination immunochemotherapy according to local standards.
Dr. Alizadeh reported disclosures related to CiberMed, Forty Seven, Janssen Oncology, Celgene, Roche/Genentech, and Gilead, as well as patent filings on ctDNA detection assigned to Stanford University.
SOURCE: Kurtz DM et al. J Clin Oncol. 2018 Aug 20. doi: 10.1200/JCO.2018.78.5246.
Measurement of circulating tumor DNA (ctDNA) could be a new and useful tool for predicting survival outcomes and response to therapy in patients with diffuse large B-cell lymphoma (DLBCL), according to authors of a recent prospective study.
Pretreatment ctDNA levels predicted 24-month event-free survival – an important disease milestone in DLBCL – as well as overall survival in the study, which included more than 200 patients at six institutions in North America and Europe.
Changes in ctDNA during treatment were prognostic for outcomes as early as 21 days into therapy, according to corresponding author Ash A. Alizadeh, MD, PhD, of Stanford (Calif.) University and his coinvestigators.
“Our data suggest that both pretreatment and dynamic assessments of ctDNA are feasible and can add to established risk factors,” Dr. Alizadeh and his coauthors reported in the Journal of Clinical Oncology.
ctDNA was detected in 98% of the 217 patients evaluated, which demonstrated the “potentially universal applicability” of this approach, they wrote in the report.
In an evaluation of pretreatment ctDNA levels, investigators found a 2.5 log haploid genome equivalents per milliliter (hGE/mL) threshold stratified patient outcomes. Event-free survival was significantly inferior at 24 months in patients with ctDNA above that threshold, with hazard ratios of 2.6 (P = .007) for frontline treatment and 2.9 (P = 0.01) for salvage.
On-treatment ctDNA levels were favorably prognostic for outcomes in patients receiving frontline therapy, according to investigators. An early molecular response (EMR), defined as a 2-log decrease in ctDNA levels after one cycle of treatment, was associated with a 24-month event-free survival of 83% versus 50% for no EMR (P = .0015).
Major molecular response (MMR), defined as a 2.5-log drop in ctDNA after two cycles of treatment, was associated with a 24-month event-free survival of 82% versus 46% for no MMR in patients on frontline therapy (P less than .001).
In one cohort of patients receiving salvage therapy, EMR also predicted superior 24-month event-free survival, according to investigators.
The EMR measure was also favorably prognostic for overall survival in both the frontline and salvage settings.
The prognostic value of measuring ctDNA was independent of International Prognostic Index (IPI) and interim PET/CT studies, results of multivariable analysis showed.
Patients had “excellent outcomes” if they had both molecular response and favorable interim PET results, and conversely, patients were at “extremely high risk” for treatment failure if they had no molecular response and a positive PET scan.
“The identification of patients at exceptionally high risk (i.e., interim PET/CT positive and not achieving EMR/MMR) could provide an opportunity for early intervention with alternative treatments, including autologous bone marrow transplantation or chimeric antigen receptor T cells,” the researchers wrote.
Patients in the study were all treated with combination immunochemotherapy according to local standards.
Dr. Alizadeh reported disclosures related to CiberMed, Forty Seven, Janssen Oncology, Celgene, Roche/Genentech, and Gilead, as well as patent filings on ctDNA detection assigned to Stanford University.
SOURCE: Kurtz DM et al. J Clin Oncol. 2018 Aug 20. doi: 10.1200/JCO.2018.78.5246.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point:
Major finding: Early molecular response (a 2-log decrease in ctDNA levels after one treatment cycle) was associated with a 24-month event-free survival of 83% versus 50% for no early molecular response (P = .0015).
Study details: Prospective analysis of pretreatment and dynamic on-treatment ctDNA levels in patients with DLBCL who received standard immunochemotherapy.
Disclosures: Study authors reported disclosures related to CiberMed, Forty Seven, Janssen Oncology, Celgene, Roche/Genentech, and Gilead, among others.
Source: Kurtz DM et al. J Clin Oncol. 2018 Aug 20. doi: 10.1200/JCO.2018.78.5246.
FDA approves ibrutinib with rituximab in Waldenström’s macroglobulinemia
The Food and Drug Administration has approved ibrutinib (Imbruvica) for use in combination with rituximab to treat adults with Waldenström’s macroglobulinemia (WM).
Ibrutinib was approved for use as a single agent in adults with WM in January 2015.
The latest approval was supported by the phase 3 iNNOVATE trial, in which researchers compared ibrutinib plus rituximab to rituximab alone in patients with previously untreated or relapsed/refractory WM.
Results from iNNOVATE were presented at the 2018 annual meeting of the American Society of Clinical Oncology and simultaneously published in the New England Journal of Medicine (2018;378:2399-2410).
The 30-month progression-free survival rates were 82% in the ibrutinib arm and 28% in the placebo arm. The median progression-free survival was not reached in the ibrutinib arm and was 20.3 months in the placebo arm (hazard ratio, 0.20; P less than .0001).
The 30-month overall survival rates were 94% in the ibrutinib arm and 92% in the placebo arm.
Grade 3 or higher treatment-emergent adverse events (AEs) occurred in 60% of patients in the ibrutinib arm and 61% in the placebo arm. Serious AEs occurred in 43% and 33%, respectively. There were no fatal AEs in the ibrutinib arm and three in the rituximab arm.
Ibrutinib is jointly developed and commercialized by Pharmacyclics, an AbbVie company, and Janssen Biotech.
The Food and Drug Administration has approved ibrutinib (Imbruvica) for use in combination with rituximab to treat adults with Waldenström’s macroglobulinemia (WM).
Ibrutinib was approved for use as a single agent in adults with WM in January 2015.
The latest approval was supported by the phase 3 iNNOVATE trial, in which researchers compared ibrutinib plus rituximab to rituximab alone in patients with previously untreated or relapsed/refractory WM.
Results from iNNOVATE were presented at the 2018 annual meeting of the American Society of Clinical Oncology and simultaneously published in the New England Journal of Medicine (2018;378:2399-2410).
The 30-month progression-free survival rates were 82% in the ibrutinib arm and 28% in the placebo arm. The median progression-free survival was not reached in the ibrutinib arm and was 20.3 months in the placebo arm (hazard ratio, 0.20; P less than .0001).
The 30-month overall survival rates were 94% in the ibrutinib arm and 92% in the placebo arm.
Grade 3 or higher treatment-emergent adverse events (AEs) occurred in 60% of patients in the ibrutinib arm and 61% in the placebo arm. Serious AEs occurred in 43% and 33%, respectively. There were no fatal AEs in the ibrutinib arm and three in the rituximab arm.
Ibrutinib is jointly developed and commercialized by Pharmacyclics, an AbbVie company, and Janssen Biotech.
The Food and Drug Administration has approved ibrutinib (Imbruvica) for use in combination with rituximab to treat adults with Waldenström’s macroglobulinemia (WM).
Ibrutinib was approved for use as a single agent in adults with WM in January 2015.
The latest approval was supported by the phase 3 iNNOVATE trial, in which researchers compared ibrutinib plus rituximab to rituximab alone in patients with previously untreated or relapsed/refractory WM.
Results from iNNOVATE were presented at the 2018 annual meeting of the American Society of Clinical Oncology and simultaneously published in the New England Journal of Medicine (2018;378:2399-2410).
The 30-month progression-free survival rates were 82% in the ibrutinib arm and 28% in the placebo arm. The median progression-free survival was not reached in the ibrutinib arm and was 20.3 months in the placebo arm (hazard ratio, 0.20; P less than .0001).
The 30-month overall survival rates were 94% in the ibrutinib arm and 92% in the placebo arm.
Grade 3 or higher treatment-emergent adverse events (AEs) occurred in 60% of patients in the ibrutinib arm and 61% in the placebo arm. Serious AEs occurred in 43% and 33%, respectively. There were no fatal AEs in the ibrutinib arm and three in the rituximab arm.
Ibrutinib is jointly developed and commercialized by Pharmacyclics, an AbbVie company, and Janssen Biotech.
Innovative Devices Could Help Keep Suicidal Vets Safer
In 2014, 68% of male veterans and 41% of female veterans who committed suicide used a firearm. Research suggests that most suicidal crises pass within minutes to hours: Building in time and space between a suicidal impulse and access to a gun can be a safety valve.
The VA Challenge Team launched an innovation contest for novel and effective approaches using gun-safety mechanisms to prevent suicide, injury, and accidents. One main criterion: the device or system must allow for 100% voluntary control (implementation, suspension, decommissioning) by the veteran.
The Challenge team was looking for solutions that would be inexpensive, applicable for at-home use, not impede responsible access to the weapon, and provide education about gun safety. The winners were:
- First place—Barret Schlegelmilch, for the DuoBox, a mechanical device that provides inexpensive, secure and reliable weapon storage and encourages responsible weapon access with 2 people present.
- Second place—Timothy Oh, Christine Tate, and Jorel Lalicki, for their “open environment” biometric safe that includes fingerprint authentication and other features to enhance control of access.
- Third place—Kathleen Gilligan and Leslie Bodi, for the Sentinel, a mobile application that helps veterans connect with peers in an innovative “buddy system” so they know they are not alone in a crisis. The app also controls Bluetooth-enabled gun-lock boxes and has unique features such as a time-lock and automated emergency calling.
The winners received cash awards, as well as access to VA resources, such as subject matter experts, for any potential follow-on design and development.
In 2014, 68% of male veterans and 41% of female veterans who committed suicide used a firearm. Research suggests that most suicidal crises pass within minutes to hours: Building in time and space between a suicidal impulse and access to a gun can be a safety valve.
The VA Challenge Team launched an innovation contest for novel and effective approaches using gun-safety mechanisms to prevent suicide, injury, and accidents. One main criterion: the device or system must allow for 100% voluntary control (implementation, suspension, decommissioning) by the veteran.
The Challenge team was looking for solutions that would be inexpensive, applicable for at-home use, not impede responsible access to the weapon, and provide education about gun safety. The winners were:
- First place—Barret Schlegelmilch, for the DuoBox, a mechanical device that provides inexpensive, secure and reliable weapon storage and encourages responsible weapon access with 2 people present.
- Second place—Timothy Oh, Christine Tate, and Jorel Lalicki, for their “open environment” biometric safe that includes fingerprint authentication and other features to enhance control of access.
- Third place—Kathleen Gilligan and Leslie Bodi, for the Sentinel, a mobile application that helps veterans connect with peers in an innovative “buddy system” so they know they are not alone in a crisis. The app also controls Bluetooth-enabled gun-lock boxes and has unique features such as a time-lock and automated emergency calling.
The winners received cash awards, as well as access to VA resources, such as subject matter experts, for any potential follow-on design and development.
In 2014, 68% of male veterans and 41% of female veterans who committed suicide used a firearm. Research suggests that most suicidal crises pass within minutes to hours: Building in time and space between a suicidal impulse and access to a gun can be a safety valve.
The VA Challenge Team launched an innovation contest for novel and effective approaches using gun-safety mechanisms to prevent suicide, injury, and accidents. One main criterion: the device or system must allow for 100% voluntary control (implementation, suspension, decommissioning) by the veteran.
The Challenge team was looking for solutions that would be inexpensive, applicable for at-home use, not impede responsible access to the weapon, and provide education about gun safety. The winners were:
- First place—Barret Schlegelmilch, for the DuoBox, a mechanical device that provides inexpensive, secure and reliable weapon storage and encourages responsible weapon access with 2 people present.
- Second place—Timothy Oh, Christine Tate, and Jorel Lalicki, for their “open environment” biometric safe that includes fingerprint authentication and other features to enhance control of access.
- Third place—Kathleen Gilligan and Leslie Bodi, for the Sentinel, a mobile application that helps veterans connect with peers in an innovative “buddy system” so they know they are not alone in a crisis. The app also controls Bluetooth-enabled gun-lock boxes and has unique features such as a time-lock and automated emergency calling.
The winners received cash awards, as well as access to VA resources, such as subject matter experts, for any potential follow-on design and development.
Live attenuated flu vaccine gets ACIP nod for 2018-2019 season
The latest seasonal influenza vaccine recommendations from the Advisory Committee on Immunization Practices provide several key updates that will impact clinical practice in the 2018-2019 influenza season.
Of note, , following two seasons in which the committee recommended it not be used.
ACIP also updated its recommendations for individuals with a history of egg allergy, described the vaccine strains chosen for 2018-2019 season, and detailed the changes in age indications for Afluria Quadrivalent and Fluarix Quadrivalent that have been made since publication of its previous guidelines.
Published in MMWR Recommendations and Reports, the updated ACIP recommendations reflect discussions and decisions from the three public meetings of ACIP that have taken place since the last annual update.
All individuals 6 months of age and older who have no contraindications to influenza vaccine should receive routine annual influenza vaccine, ACIP also said in its report, reinforcing a key recommendation that has been in place since 2010.
“To avoid missed opportunities for vaccination, providers should offer vaccination during routine health care visits and hospitalizations,” wrote authors of the report, including lead author Lisa A. Grohskopf, MD, of the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta.
Dr. Grohskopf and coauthors made no specific recommendations on which vaccine to use. They said providers should choose licensed, age-appropriate recommended vaccines expected to be available for the 2018-2019 season, including inactivated influenza vaccines (IIV), a recombinant influenza vaccine (RIV4), and the LAIV option.
FluMist Quadrivalent, the one LAIV product expected to be available for the 2018-2019 season, is licensed for individuals aged 2-49 years.
In its deliberations over the updated LAIV recommendation, ACIP reviewed observational data from previous seasons suggesting that the vaccine was poorly effective, and significantly less effective than IIV, against influenza A(H1N1) pdm09 viruses.
The current formulation of FluMist includes a new H1N1pdm09-like vaccine virus. While no effectiveness estimates were available at the time of review, ACIP said it did consider manufacturer data on shedding and immunogenicity for the current vaccine in children between the ages of 24 months through less than 4 years.
“These data suggest that this new H1N1pdm09-like virus has improved replicative fitness over previous H1N1pdm09-like viruses included in LAIV,” Dr. Grohskopf and colleagues wrote.
Individuals with an egg allergy history also can receive any licensed, recommended, age-appropriate IIV, RIV, or LAIV vaccine, said ACIP. This updated recommendation was based in part on the committee’s review and discussion of three studies that showed no cases of anaphylaxis in egg-allergic children receiving LAIV.
The ACIP recommendation update also outlines the strains selected earlier this year for the 2018-2019 season. Trivalent influenza vaccines in the United States will include an A/Michigan/45/2015 (H1N1) pdm09–like virus, an A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus, and a B/Colorado/06/2017–like virus (Victoria lineage). Quadrivalent vaccines will include those strains plus a B/Phuket/3073/2013–like virus (Yamagata lineage).
The report also acknowledges the recent expansion of age indication for two vaccines that have occurred since the last ACIP recommendations.
Afluria Quadrivalent was previously licensed for individuals 18 years of age and older. In August 2017, the Food and Drug Administration approved expansion of the indication to individuals 5 years of age or older. In January 2018, FDA approved expansion of the Fluarix Quadrivalent indication, previously licensed for age 3 and older, to individuals 6 months and older.
Report coauthor Emmanuel B. Walter disclosed grants from Novavax and Merck. The remaining report authors reported no relevant financial disclosures.
SOURCE: Grohskopf LA et al. MMWR Recomm Rep. 2018 Aug 24;67(3):1-20.
The latest seasonal influenza vaccine recommendations from the Advisory Committee on Immunization Practices provide several key updates that will impact clinical practice in the 2018-2019 influenza season.
Of note, , following two seasons in which the committee recommended it not be used.
ACIP also updated its recommendations for individuals with a history of egg allergy, described the vaccine strains chosen for 2018-2019 season, and detailed the changes in age indications for Afluria Quadrivalent and Fluarix Quadrivalent that have been made since publication of its previous guidelines.
Published in MMWR Recommendations and Reports, the updated ACIP recommendations reflect discussions and decisions from the three public meetings of ACIP that have taken place since the last annual update.
All individuals 6 months of age and older who have no contraindications to influenza vaccine should receive routine annual influenza vaccine, ACIP also said in its report, reinforcing a key recommendation that has been in place since 2010.
“To avoid missed opportunities for vaccination, providers should offer vaccination during routine health care visits and hospitalizations,” wrote authors of the report, including lead author Lisa A. Grohskopf, MD, of the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta.
Dr. Grohskopf and coauthors made no specific recommendations on which vaccine to use. They said providers should choose licensed, age-appropriate recommended vaccines expected to be available for the 2018-2019 season, including inactivated influenza vaccines (IIV), a recombinant influenza vaccine (RIV4), and the LAIV option.
FluMist Quadrivalent, the one LAIV product expected to be available for the 2018-2019 season, is licensed for individuals aged 2-49 years.
In its deliberations over the updated LAIV recommendation, ACIP reviewed observational data from previous seasons suggesting that the vaccine was poorly effective, and significantly less effective than IIV, against influenza A(H1N1) pdm09 viruses.
The current formulation of FluMist includes a new H1N1pdm09-like vaccine virus. While no effectiveness estimates were available at the time of review, ACIP said it did consider manufacturer data on shedding and immunogenicity for the current vaccine in children between the ages of 24 months through less than 4 years.
“These data suggest that this new H1N1pdm09-like virus has improved replicative fitness over previous H1N1pdm09-like viruses included in LAIV,” Dr. Grohskopf and colleagues wrote.
Individuals with an egg allergy history also can receive any licensed, recommended, age-appropriate IIV, RIV, or LAIV vaccine, said ACIP. This updated recommendation was based in part on the committee’s review and discussion of three studies that showed no cases of anaphylaxis in egg-allergic children receiving LAIV.
The ACIP recommendation update also outlines the strains selected earlier this year for the 2018-2019 season. Trivalent influenza vaccines in the United States will include an A/Michigan/45/2015 (H1N1) pdm09–like virus, an A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus, and a B/Colorado/06/2017–like virus (Victoria lineage). Quadrivalent vaccines will include those strains plus a B/Phuket/3073/2013–like virus (Yamagata lineage).
The report also acknowledges the recent expansion of age indication for two vaccines that have occurred since the last ACIP recommendations.
Afluria Quadrivalent was previously licensed for individuals 18 years of age and older. In August 2017, the Food and Drug Administration approved expansion of the indication to individuals 5 years of age or older. In January 2018, FDA approved expansion of the Fluarix Quadrivalent indication, previously licensed for age 3 and older, to individuals 6 months and older.
Report coauthor Emmanuel B. Walter disclosed grants from Novavax and Merck. The remaining report authors reported no relevant financial disclosures.
SOURCE: Grohskopf LA et al. MMWR Recomm Rep. 2018 Aug 24;67(3):1-20.
The latest seasonal influenza vaccine recommendations from the Advisory Committee on Immunization Practices provide several key updates that will impact clinical practice in the 2018-2019 influenza season.
Of note, , following two seasons in which the committee recommended it not be used.
ACIP also updated its recommendations for individuals with a history of egg allergy, described the vaccine strains chosen for 2018-2019 season, and detailed the changes in age indications for Afluria Quadrivalent and Fluarix Quadrivalent that have been made since publication of its previous guidelines.
Published in MMWR Recommendations and Reports, the updated ACIP recommendations reflect discussions and decisions from the three public meetings of ACIP that have taken place since the last annual update.
All individuals 6 months of age and older who have no contraindications to influenza vaccine should receive routine annual influenza vaccine, ACIP also said in its report, reinforcing a key recommendation that has been in place since 2010.
“To avoid missed opportunities for vaccination, providers should offer vaccination during routine health care visits and hospitalizations,” wrote authors of the report, including lead author Lisa A. Grohskopf, MD, of the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta.
Dr. Grohskopf and coauthors made no specific recommendations on which vaccine to use. They said providers should choose licensed, age-appropriate recommended vaccines expected to be available for the 2018-2019 season, including inactivated influenza vaccines (IIV), a recombinant influenza vaccine (RIV4), and the LAIV option.
FluMist Quadrivalent, the one LAIV product expected to be available for the 2018-2019 season, is licensed for individuals aged 2-49 years.
In its deliberations over the updated LAIV recommendation, ACIP reviewed observational data from previous seasons suggesting that the vaccine was poorly effective, and significantly less effective than IIV, against influenza A(H1N1) pdm09 viruses.
The current formulation of FluMist includes a new H1N1pdm09-like vaccine virus. While no effectiveness estimates were available at the time of review, ACIP said it did consider manufacturer data on shedding and immunogenicity for the current vaccine in children between the ages of 24 months through less than 4 years.
“These data suggest that this new H1N1pdm09-like virus has improved replicative fitness over previous H1N1pdm09-like viruses included in LAIV,” Dr. Grohskopf and colleagues wrote.
Individuals with an egg allergy history also can receive any licensed, recommended, age-appropriate IIV, RIV, or LAIV vaccine, said ACIP. This updated recommendation was based in part on the committee’s review and discussion of three studies that showed no cases of anaphylaxis in egg-allergic children receiving LAIV.
The ACIP recommendation update also outlines the strains selected earlier this year for the 2018-2019 season. Trivalent influenza vaccines in the United States will include an A/Michigan/45/2015 (H1N1) pdm09–like virus, an A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus, and a B/Colorado/06/2017–like virus (Victoria lineage). Quadrivalent vaccines will include those strains plus a B/Phuket/3073/2013–like virus (Yamagata lineage).
The report also acknowledges the recent expansion of age indication for two vaccines that have occurred since the last ACIP recommendations.
Afluria Quadrivalent was previously licensed for individuals 18 years of age and older. In August 2017, the Food and Drug Administration approved expansion of the indication to individuals 5 years of age or older. In January 2018, FDA approved expansion of the Fluarix Quadrivalent indication, previously licensed for age 3 and older, to individuals 6 months and older.
Report coauthor Emmanuel B. Walter disclosed grants from Novavax and Merck. The remaining report authors reported no relevant financial disclosures.
SOURCE: Grohskopf LA et al. MMWR Recomm Rep. 2018 Aug 24;67(3):1-20.
FROM MMWR
Etravirine Lowers Risk of Hospitalization for Patients With HIV
When all 3 original classes of antiretroviral drugs no longer suppress viral load in a patient with HIV, the next step may be a new drug like etravirine (ETR), a nonnucleoside reverse transcriptase inhibitor (NNRTI). And, according to a French study, that could be a good way of keeping patients out of the hospital.
Using data from the French Hospital Database on HIV (FHDH), researchers analyzed hospitalization rates among heavily treated HIV-1 infected patients on failing regimens between 2005 (etravirine became available in France in 2006) and 2011. They compared 2 groups of patients: those who had received ETR plus a ritonavir-boosted protease inhibitor (PI) and those who had not. The primary endpoint of the study was hospitalization, divided by AIDS-defining cause and non–AIDS-defining cause.
Of 3,884 patients who had been exposed to at least 2 nucleoside reverse transcriptase inhibitors (NRTI), 2 PIs, and 1 NNRTI, 838 received ETR + PI.
During 13,986 person-years of follow-up, there were 2,484 hospitalizations among 956 patients: 617 were from an AIDS-defining cause in 301 patients, and 1,867 from a non–AIDS-defining cause in 828 patients.
The ETR + PI was associated with a 20% reduction in the hospitalization rate, mainly due to the reduction in AIDS hospitalizations. The researchers suggest that the clinical benefit of ETR could be explained by a high rate of virologic suppression (62% at month 6) and excellent tolerability. The FHDH did not include adherence data, but adherence is “unlikely” to explain the better outcome, the researchers say, given that ETR is a twice-daily drug, which may lead to slightly lower adherence than does a once-daily regimen.
The is the first study, to their knowledge, the researchers say, to focus on the risk of hospitalizations in current clinical practice and to show a positive effect.
Source:
Potard V, Goujard C, Valantin MA, et al. BMC Infect Dis. 2018;8:326.
doi: 10.1186/s12879-018-3231-5.
When all 3 original classes of antiretroviral drugs no longer suppress viral load in a patient with HIV, the next step may be a new drug like etravirine (ETR), a nonnucleoside reverse transcriptase inhibitor (NNRTI). And, according to a French study, that could be a good way of keeping patients out of the hospital.
Using data from the French Hospital Database on HIV (FHDH), researchers analyzed hospitalization rates among heavily treated HIV-1 infected patients on failing regimens between 2005 (etravirine became available in France in 2006) and 2011. They compared 2 groups of patients: those who had received ETR plus a ritonavir-boosted protease inhibitor (PI) and those who had not. The primary endpoint of the study was hospitalization, divided by AIDS-defining cause and non–AIDS-defining cause.
Of 3,884 patients who had been exposed to at least 2 nucleoside reverse transcriptase inhibitors (NRTI), 2 PIs, and 1 NNRTI, 838 received ETR + PI.
During 13,986 person-years of follow-up, there were 2,484 hospitalizations among 956 patients: 617 were from an AIDS-defining cause in 301 patients, and 1,867 from a non–AIDS-defining cause in 828 patients.
The ETR + PI was associated with a 20% reduction in the hospitalization rate, mainly due to the reduction in AIDS hospitalizations. The researchers suggest that the clinical benefit of ETR could be explained by a high rate of virologic suppression (62% at month 6) and excellent tolerability. The FHDH did not include adherence data, but adherence is “unlikely” to explain the better outcome, the researchers say, given that ETR is a twice-daily drug, which may lead to slightly lower adherence than does a once-daily regimen.
The is the first study, to their knowledge, the researchers say, to focus on the risk of hospitalizations in current clinical practice and to show a positive effect.
Source:
Potard V, Goujard C, Valantin MA, et al. BMC Infect Dis. 2018;8:326.
doi: 10.1186/s12879-018-3231-5.
When all 3 original classes of antiretroviral drugs no longer suppress viral load in a patient with HIV, the next step may be a new drug like etravirine (ETR), a nonnucleoside reverse transcriptase inhibitor (NNRTI). And, according to a French study, that could be a good way of keeping patients out of the hospital.
Using data from the French Hospital Database on HIV (FHDH), researchers analyzed hospitalization rates among heavily treated HIV-1 infected patients on failing regimens between 2005 (etravirine became available in France in 2006) and 2011. They compared 2 groups of patients: those who had received ETR plus a ritonavir-boosted protease inhibitor (PI) and those who had not. The primary endpoint of the study was hospitalization, divided by AIDS-defining cause and non–AIDS-defining cause.
Of 3,884 patients who had been exposed to at least 2 nucleoside reverse transcriptase inhibitors (NRTI), 2 PIs, and 1 NNRTI, 838 received ETR + PI.
During 13,986 person-years of follow-up, there were 2,484 hospitalizations among 956 patients: 617 were from an AIDS-defining cause in 301 patients, and 1,867 from a non–AIDS-defining cause in 828 patients.
The ETR + PI was associated with a 20% reduction in the hospitalization rate, mainly due to the reduction in AIDS hospitalizations. The researchers suggest that the clinical benefit of ETR could be explained by a high rate of virologic suppression (62% at month 6) and excellent tolerability. The FHDH did not include adherence data, but adherence is “unlikely” to explain the better outcome, the researchers say, given that ETR is a twice-daily drug, which may lead to slightly lower adherence than does a once-daily regimen.
The is the first study, to their knowledge, the researchers say, to focus on the risk of hospitalizations in current clinical practice and to show a positive effect.
Source:
Potard V, Goujard C, Valantin MA, et al. BMC Infect Dis. 2018;8:326.
doi: 10.1186/s12879-018-3231-5.
Combo treatment yields MRD-negative remissions in CLL
The combination of the anti-CD20 antibody obinutuzumab and venetoclax in chronic lymphocytic leukemia shows a high overall response rate and compares favorably with established therapies, according to a new report.
The ongoing, open-label, phase 2 study examined the outcomes of six induction cycles, followed by up to 24 months of maintenance treatment with obinutuzumab and venetoclax, in 66 patients with chronic lymphocytic leukemia (CLL). Of the 63 patients included in the efficacy analysis, 34 (54%) had treatment-naive and 29 (46%) had relapsed or refractory disease.
After an initial debulking with two cycles of bendamustine, followed by the obinutuzumab and venetoclax treatment, researchers observed an overall response rate of 95%. By the end of the induction phase, all the treatment-naive patients responded, as did 90% of the relapsed or refractory patients. Five patients had achieved complete remission and 55 patients had a partial response, the researchers reported in Lancet Oncology.
By 15 months, both progression-free and overall survival was 100% among treatment-naive patients, while progression-free survival was 83% and overall survival was 90% among the relapsed or refractory patients at this point.
Researchers observed minimal residual disease (MRD) negativity in the peripheral blood of 91% of treatment-naive patients and 83% of relapsed or refractory patients.
The combination of venetoclax and obinutuzumab was chosen based on earlier trial data, which suggested a synergy between venetoclax and the less-potent anti-CD20 antibody rituximab.
Paula Cramer, MD, from the German CLL Study Group at University Hospital, Cologne, and her coauthors described the efficacy of the venetoclax and obinutuzumab combination as “encouraging.”
“The combination of venetoclax and obinutuzumab yields fast responses with MRD-negative remissions in most patients,” they wrote. “Based on the experience with venetoclax combined with rituximab in another trial and with venetoclax and obinutuzumab in this and another study, these deep, MRD-negative remissions seem to last for a substantial time after treatment termination.”
Of the 677 adverse events, 427 (63%) were deemed to be related to the study treatment, and 69 of these were serious adverse events.
The most common of these were infections, experienced by four patients during the debulking with bendamustine, and 18 cases in 11 patients during the induction treatment. This included pneumonia, sepsis and cytomegalovirus infection, as well as neutropenia and thrombocytopenia.
Six patients also experienced infusion-related reactions, four had coronary artery disorder – one during debulking and three during induction – and there were three cases of neoplasms.
Five patients in the relapsed or refractory group died; three of sepsis related to study treatment, and two from unrelated Richter’s transformation.
“With three deaths from sepsis in 66 enrolled patients, the treatment-related mortality seems high; however, in cases of low patient numbers, a few patients can have a substantial effect on the overall results,” the researchers wrote.
The study was funded by F Hoffmann-La Roche and AbbVie. Several authors reported research funding, grants, honoraria and other support from the pharmaceutical industry, including from the study sponsors.
SOURCE: Cramer P et al. Lancet Oncol. 2018 Aug 13. doi: 10.1016/S1470-2045(18)30414-5.
The combination of the anti-CD20 antibody obinutuzumab and venetoclax in chronic lymphocytic leukemia shows a high overall response rate and compares favorably with established therapies, according to a new report.
The ongoing, open-label, phase 2 study examined the outcomes of six induction cycles, followed by up to 24 months of maintenance treatment with obinutuzumab and venetoclax, in 66 patients with chronic lymphocytic leukemia (CLL). Of the 63 patients included in the efficacy analysis, 34 (54%) had treatment-naive and 29 (46%) had relapsed or refractory disease.
After an initial debulking with two cycles of bendamustine, followed by the obinutuzumab and venetoclax treatment, researchers observed an overall response rate of 95%. By the end of the induction phase, all the treatment-naive patients responded, as did 90% of the relapsed or refractory patients. Five patients had achieved complete remission and 55 patients had a partial response, the researchers reported in Lancet Oncology.
By 15 months, both progression-free and overall survival was 100% among treatment-naive patients, while progression-free survival was 83% and overall survival was 90% among the relapsed or refractory patients at this point.
Researchers observed minimal residual disease (MRD) negativity in the peripheral blood of 91% of treatment-naive patients and 83% of relapsed or refractory patients.
The combination of venetoclax and obinutuzumab was chosen based on earlier trial data, which suggested a synergy between venetoclax and the less-potent anti-CD20 antibody rituximab.
Paula Cramer, MD, from the German CLL Study Group at University Hospital, Cologne, and her coauthors described the efficacy of the venetoclax and obinutuzumab combination as “encouraging.”
“The combination of venetoclax and obinutuzumab yields fast responses with MRD-negative remissions in most patients,” they wrote. “Based on the experience with venetoclax combined with rituximab in another trial and with venetoclax and obinutuzumab in this and another study, these deep, MRD-negative remissions seem to last for a substantial time after treatment termination.”
Of the 677 adverse events, 427 (63%) were deemed to be related to the study treatment, and 69 of these were serious adverse events.
The most common of these were infections, experienced by four patients during the debulking with bendamustine, and 18 cases in 11 patients during the induction treatment. This included pneumonia, sepsis and cytomegalovirus infection, as well as neutropenia and thrombocytopenia.
Six patients also experienced infusion-related reactions, four had coronary artery disorder – one during debulking and three during induction – and there were three cases of neoplasms.
Five patients in the relapsed or refractory group died; three of sepsis related to study treatment, and two from unrelated Richter’s transformation.
“With three deaths from sepsis in 66 enrolled patients, the treatment-related mortality seems high; however, in cases of low patient numbers, a few patients can have a substantial effect on the overall results,” the researchers wrote.
The study was funded by F Hoffmann-La Roche and AbbVie. Several authors reported research funding, grants, honoraria and other support from the pharmaceutical industry, including from the study sponsors.
SOURCE: Cramer P et al. Lancet Oncol. 2018 Aug 13. doi: 10.1016/S1470-2045(18)30414-5.
The combination of the anti-CD20 antibody obinutuzumab and venetoclax in chronic lymphocytic leukemia shows a high overall response rate and compares favorably with established therapies, according to a new report.
The ongoing, open-label, phase 2 study examined the outcomes of six induction cycles, followed by up to 24 months of maintenance treatment with obinutuzumab and venetoclax, in 66 patients with chronic lymphocytic leukemia (CLL). Of the 63 patients included in the efficacy analysis, 34 (54%) had treatment-naive and 29 (46%) had relapsed or refractory disease.
After an initial debulking with two cycles of bendamustine, followed by the obinutuzumab and venetoclax treatment, researchers observed an overall response rate of 95%. By the end of the induction phase, all the treatment-naive patients responded, as did 90% of the relapsed or refractory patients. Five patients had achieved complete remission and 55 patients had a partial response, the researchers reported in Lancet Oncology.
By 15 months, both progression-free and overall survival was 100% among treatment-naive patients, while progression-free survival was 83% and overall survival was 90% among the relapsed or refractory patients at this point.
Researchers observed minimal residual disease (MRD) negativity in the peripheral blood of 91% of treatment-naive patients and 83% of relapsed or refractory patients.
The combination of venetoclax and obinutuzumab was chosen based on earlier trial data, which suggested a synergy between venetoclax and the less-potent anti-CD20 antibody rituximab.
Paula Cramer, MD, from the German CLL Study Group at University Hospital, Cologne, and her coauthors described the efficacy of the venetoclax and obinutuzumab combination as “encouraging.”
“The combination of venetoclax and obinutuzumab yields fast responses with MRD-negative remissions in most patients,” they wrote. “Based on the experience with venetoclax combined with rituximab in another trial and with venetoclax and obinutuzumab in this and another study, these deep, MRD-negative remissions seem to last for a substantial time after treatment termination.”
Of the 677 adverse events, 427 (63%) were deemed to be related to the study treatment, and 69 of these were serious adverse events.
The most common of these were infections, experienced by four patients during the debulking with bendamustine, and 18 cases in 11 patients during the induction treatment. This included pneumonia, sepsis and cytomegalovirus infection, as well as neutropenia and thrombocytopenia.
Six patients also experienced infusion-related reactions, four had coronary artery disorder – one during debulking and three during induction – and there were three cases of neoplasms.
Five patients in the relapsed or refractory group died; three of sepsis related to study treatment, and two from unrelated Richter’s transformation.
“With three deaths from sepsis in 66 enrolled patients, the treatment-related mortality seems high; however, in cases of low patient numbers, a few patients can have a substantial effect on the overall results,” the researchers wrote.
The study was funded by F Hoffmann-La Roche and AbbVie. Several authors reported research funding, grants, honoraria and other support from the pharmaceutical industry, including from the study sponsors.
SOURCE: Cramer P et al. Lancet Oncol. 2018 Aug 13. doi: 10.1016/S1470-2045(18)30414-5.
FROM LANCET ONCOLOGY
Key clinical point:
Major finding: The overall response rate for obinutuzumab plus venetoclax in CLL was 95%.
Study details: An ongoing, phase 2, open-label trial in 66 patients with chronic lymphocytic leukemia.
Disclosures: The study was funded by F Hoffmann-La Roche and AbbVie. Several authors reported research funding, grants, honoraria, and other support from the pharmaceutical industry, including from the study sponsors.
Source: Cramer P et al. Lancet Oncol. 2018 Aug 13. doi: 10.1016/S1470-2045(18)30414-5.