Andrew D. Bowser

Compared with younger patients, elderly patients admitted for acute biliary pancreatitis have increased rates of severe acute pancreatitis and mortality, according to an analysis of a nationally representative database.

Mortality was almost three times as high in elderly patients after stringent matching for confounding variables, wrote researcher Kishan Patel, MD, of the Ohio State University, Columbus, and coauthors.

These findings represent a “current health care concern,” since the elderly population in the United States is expected to double within the next several decades and the prevalence of acute pancreatitis is on the rise, Dr. Patel and colleagues wrote in a report on the analysis in the Journal of Clinical Gastroenterology.

The analysis is the first, to the investigators’ knowledge, that addresses national-level outcomes associated with acute biliary pancreatitis in elderly patients.

To evaluate clinical outcomes of elderly patients with acute biliary pancreatitis, Dr. Patel and colleagues queried the Nationwide Readmissions Database, which is the largest inpatient readmission database in the United States.

The investigators looked at outcomes associated with index hospitalizations, defined as a patient’s first hospitalization in a calendar year, and found 184,763 adult patients who received a diagnosis of acute biliary pancreatitis between 2011 and 2014. Of those, 41% were elderly.

The mortality rate associated with the index admission was 1.96% (n = 356) for the elderly patients, compared with just 0.32% (n = 1,473) for nonelderly patients (P less than .001), according to the report.

Mortality was increased in the elderly versus nonelderly patients, with an odds ratio of 2.8 (95% CI, 2.2-3.5), according to results of a propensity score matched analysis. Likewise, severe acute pancreatitis was increased in the elderly, with an OR of 1.2 (95% CI: 1.1-1.3) in that analysis.

By contrast, patient age did not impact 30-day readmission rates, according to results of a multivariate analysis that adjusted for confounding factors.

Mortality and severe acute pancreatitis both increased with age within the elderly cohort, further multivariate analysis showed. For example, the ORs for mortality were 1.39 for patients aged 75-84 years and 2.21 for patients aged 85 years and older, the results show.

The elderly population in the United States is expected to almost double by 2050, rising from 48 to 88 million, Dr. Patel and colleagues said. The number of those aged 85 years or older is expected to increase from 5.9 to 18 million by 2050, at which time they will make up nearly 5% of the total U.S. population.

“This specific demographic is more susceptible to common medical ailments, more troubling is acute pancreatitis is one of the most frequent causes of hospitalization in gastroenterology,” Dr. Patel and colleagues wrote.

Dr. Patel and coauthors reported no conflicts of interest related to the analysis.

SOURCE: Patel K et al. J Clin Gastroenterol. 2018 Aug 28. doi: 10.1097/MCG.0000000000001108.

Compared with younger patients, elderly patients admitted for acute biliary pancreatitis have increased rates of severe acute pancreatitis and mortality, according to an analysis of a nationally representative database.

Mortality was almost three times as high in elderly patients after stringent matching for confounding variables, wrote researcher Kishan Patel, MD, of the Ohio State University, Columbus, and coauthors.

These findings represent a “current health care concern,” since the elderly population in the United States is expected to double within the next several decades and the prevalence of acute pancreatitis is on the rise, Dr. Patel and colleagues wrote in a report on the analysis in the Journal of Clinical Gastroenterology.

The analysis is the first, to the investigators’ knowledge, that addresses national-level outcomes associated with acute biliary pancreatitis in elderly patients.

To evaluate clinical outcomes of elderly patients with acute biliary pancreatitis, Dr. Patel and colleagues queried the Nationwide Readmissions Database, which is the largest inpatient readmission database in the United States.

The investigators looked at outcomes associated with index hospitalizations, defined as a patient’s first hospitalization in a calendar year, and found 184,763 adult patients who received a diagnosis of acute biliary pancreatitis between 2011 and 2014. Of those, 41% were elderly.

The mortality rate associated with the index admission was 1.96% (n = 356) for the elderly patients, compared with just 0.32% (n = 1,473) for nonelderly patients (P less than .001), according to the report.

Mortality was increased in the elderly versus nonelderly patients, with an odds ratio of 2.8 (95% CI, 2.2-3.5), according to results of a propensity score matched analysis. Likewise, severe acute pancreatitis was increased in the elderly, with an OR of 1.2 (95% CI: 1.1-1.3) in that analysis.

By contrast, patient age did not impact 30-day readmission rates, according to results of a multivariate analysis that adjusted for confounding factors.

Mortality and severe acute pancreatitis both increased with age within the elderly cohort, further multivariate analysis showed. For example, the ORs for mortality were 1.39 for patients aged 75-84 years and 2.21 for patients aged 85 years and older, the results show.

The elderly population in the United States is expected to almost double by 2050, rising from 48 to 88 million, Dr. Patel and colleagues said. The number of those aged 85 years or older is expected to increase from 5.9 to 18 million by 2050, at which time they will make up nearly 5% of the total U.S. population.

“This specific demographic is more susceptible to common medical ailments, more troubling is acute pancreatitis is one of the most frequent causes of hospitalization in gastroenterology,” Dr. Patel and colleagues wrote.

Dr. Patel and coauthors reported no conflicts of interest related to the analysis.

SOURCE: Patel K et al. J Clin Gastroenterol. 2018 Aug 28. doi: 10.1097/MCG.0000000000001108.

Compared with younger patients, elderly patients admitted for acute biliary pancreatitis have increased rates of severe acute pancreatitis and mortality, according to an analysis of a nationally representative database.

Mortality was almost three times as high in elderly patients after stringent matching for confounding variables, wrote researcher Kishan Patel, MD, of the Ohio State University, Columbus, and coauthors.

These findings represent a “current health care concern,” since the elderly population in the United States is expected to double within the next several decades and the prevalence of acute pancreatitis is on the rise, Dr. Patel and colleagues wrote in a report on the analysis in the Journal of Clinical Gastroenterology.

The analysis is the first, to the investigators’ knowledge, that addresses national-level outcomes associated with acute biliary pancreatitis in elderly patients.

To evaluate clinical outcomes of elderly patients with acute biliary pancreatitis, Dr. Patel and colleagues queried the Nationwide Readmissions Database, which is the largest inpatient readmission database in the United States.

The investigators looked at outcomes associated with index hospitalizations, defined as a patient’s first hospitalization in a calendar year, and found 184,763 adult patients who received a diagnosis of acute biliary pancreatitis between 2011 and 2014. Of those, 41% were elderly.

The mortality rate associated with the index admission was 1.96% (n = 356) for the elderly patients, compared with just 0.32% (n = 1,473) for nonelderly patients (P less than .001), according to the report.

Mortality was increased in the elderly versus nonelderly patients, with an odds ratio of 2.8 (95% CI, 2.2-3.5), according to results of a propensity score matched analysis. Likewise, severe acute pancreatitis was increased in the elderly, with an OR of 1.2 (95% CI: 1.1-1.3) in that analysis.

By contrast, patient age did not impact 30-day readmission rates, according to results of a multivariate analysis that adjusted for confounding factors.

Mortality and severe acute pancreatitis both increased with age within the elderly cohort, further multivariate analysis showed. For example, the ORs for mortality were 1.39 for patients aged 75-84 years and 2.21 for patients aged 85 years and older, the results show.

The elderly population in the United States is expected to almost double by 2050, rising from 48 to 88 million, Dr. Patel and colleagues said. The number of those aged 85 years or older is expected to increase from 5.9 to 18 million by 2050, at which time they will make up nearly 5% of the total U.S. population.

“This specific demographic is more susceptible to common medical ailments, more troubling is acute pancreatitis is one of the most frequent causes of hospitalization in gastroenterology,” Dr. Patel and colleagues wrote.

Dr. Patel and coauthors reported no conflicts of interest related to the analysis.

SOURCE: Patel K et al. J Clin Gastroenterol. 2018 Aug 28. doi: 10.1097/MCG.0000000000001108.

Photo by Bill Branson

Escalating methotrexate (MTX) may produce better outcomes than high-dose MTX in children and young adults with T-cell acute lymphoblastic leukemia (T-ALL), according to research published in the Journal of Clinical Oncology.

Researchers compared escalating and high-dose MTX given with the augmented Berlin-Frankfurt-Munster regimen in patients with T-ALL.

Disease-free survival (DFS) and overall survival (OS) rates were significantly higher among patients who received escalating MTX.

The improved survival outcomes in this trial, AALL0434, are the “opposite effect” of what was observed in a parallel trial, AALL0232. In that trial, high-dose MTX was superior to the escalating strategy in patients with B-cell acute lymphoblastic leukemia (B-ALL).

The parallel trial design was used because of the known differences between T-ALL and B-ALL in sensitivity to MTX and pegaspargase, according to investigator Stuart S. Winter, MD, of Children’s Minnesota Minneapolis Hospital, and his coauthors.

The AALL0434 study included 1,031 T-ALL patients between 1 and 31 years of age without CNS3 disease or testicular leukemia. They were randomized to post-induction therapy that included either escalating intravenous MTX or high-dose MTX.

The escalating regimen was superior to high-dose MTX, according to investigators.

The 5-year DFS rate was 91.5% with escalating MTX and 85.3% with high-dose MTX (P=0.005). The 5-year OS rate was 93.7% and 89.4%, respectively (P=0.036).

In contrast, the parallel AALL0232 study of B-ALL patients showed that high-dose MTX produced superior 5-year event-free survival and OS. This led Dr. Winter and his colleagues to speculate on how the findings could be reconciled.

Neither trial was a strict comparison of two different MTX schedules, due to differences in doses of pegaspargase, mercaptopurine, and vincristine between arms, as well as differences in the timing of cranial radiation therapy.

Of note, patients randomized to escalated MTX had two additional doses of pegaspargase. Enhanced asparagine depletion in that arm may have prevented relapse events, the investigators said.

They also said differences in adherence could have played a role, as the cost and time burden of the escalating MTX approach are “substantially less” than the high-dose approach.

The AALL0434 trial also included a second randomization to an addition of five, 6-day cycles of nelarabine versus no nelarabine. Results of that randomization, reported earlier this year, showed that nelarabine improved DFS.

AALL0434 was supported by grants from the National Institutes of Health and by St. Baldrick’s Foundation. Dr. Winter reported relationships with Amgen and Jazz Pharmaceuticals. His coauthors reported relationships with Novo Nordisk, Tandem, Pfizer, Novartis, and TypeZero Technologies, among others.

Photo by Bill Branson

Escalating methotrexate (MTX) may produce better outcomes than high-dose MTX in children and young adults with T-cell acute lymphoblastic leukemia (T-ALL), according to research published in the Journal of Clinical Oncology.

Researchers compared escalating and high-dose MTX given with the augmented Berlin-Frankfurt-Munster regimen in patients with T-ALL.

Disease-free survival (DFS) and overall survival (OS) rates were significantly higher among patients who received escalating MTX.

The improved survival outcomes in this trial, AALL0434, are the “opposite effect” of what was observed in a parallel trial, AALL0232. In that trial, high-dose MTX was superior to the escalating strategy in patients with B-cell acute lymphoblastic leukemia (B-ALL).

The parallel trial design was used because of the known differences between T-ALL and B-ALL in sensitivity to MTX and pegaspargase, according to investigator Stuart S. Winter, MD, of Children’s Minnesota Minneapolis Hospital, and his coauthors.

The AALL0434 study included 1,031 T-ALL patients between 1 and 31 years of age without CNS3 disease or testicular leukemia. They were randomized to post-induction therapy that included either escalating intravenous MTX or high-dose MTX.

The escalating regimen was superior to high-dose MTX, according to investigators.

The 5-year DFS rate was 91.5% with escalating MTX and 85.3% with high-dose MTX (P=0.005). The 5-year OS rate was 93.7% and 89.4%, respectively (P=0.036).

In contrast, the parallel AALL0232 study of B-ALL patients showed that high-dose MTX produced superior 5-year event-free survival and OS. This led Dr. Winter and his colleagues to speculate on how the findings could be reconciled.

Neither trial was a strict comparison of two different MTX schedules, due to differences in doses of pegaspargase, mercaptopurine, and vincristine between arms, as well as differences in the timing of cranial radiation therapy.

Of note, patients randomized to escalated MTX had two additional doses of pegaspargase. Enhanced asparagine depletion in that arm may have prevented relapse events, the investigators said.

They also said differences in adherence could have played a role, as the cost and time burden of the escalating MTX approach are “substantially less” than the high-dose approach.

The AALL0434 trial also included a second randomization to an addition of five, 6-day cycles of nelarabine versus no nelarabine. Results of that randomization, reported earlier this year, showed that nelarabine improved DFS.

AALL0434 was supported by grants from the National Institutes of Health and by St. Baldrick’s Foundation. Dr. Winter reported relationships with Amgen and Jazz Pharmaceuticals. His coauthors reported relationships with Novo Nordisk, Tandem, Pfizer, Novartis, and TypeZero Technologies, among others.

Photo by Bill Branson

Escalating methotrexate (MTX) may produce better outcomes than high-dose MTX in children and young adults with T-cell acute lymphoblastic leukemia (T-ALL), according to research published in the Journal of Clinical Oncology.

Researchers compared escalating and high-dose MTX given with the augmented Berlin-Frankfurt-Munster regimen in patients with T-ALL.

Disease-free survival (DFS) and overall survival (OS) rates were significantly higher among patients who received escalating MTX.

The improved survival outcomes in this trial, AALL0434, are the “opposite effect” of what was observed in a parallel trial, AALL0232. In that trial, high-dose MTX was superior to the escalating strategy in patients with B-cell acute lymphoblastic leukemia (B-ALL).

The parallel trial design was used because of the known differences between T-ALL and B-ALL in sensitivity to MTX and pegaspargase, according to investigator Stuart S. Winter, MD, of Children’s Minnesota Minneapolis Hospital, and his coauthors.

The AALL0434 study included 1,031 T-ALL patients between 1 and 31 years of age without CNS3 disease or testicular leukemia. They were randomized to post-induction therapy that included either escalating intravenous MTX or high-dose MTX.

The escalating regimen was superior to high-dose MTX, according to investigators.

The 5-year DFS rate was 91.5% with escalating MTX and 85.3% with high-dose MTX (P=0.005). The 5-year OS rate was 93.7% and 89.4%, respectively (P=0.036).

In contrast, the parallel AALL0232 study of B-ALL patients showed that high-dose MTX produced superior 5-year event-free survival and OS. This led Dr. Winter and his colleagues to speculate on how the findings could be reconciled.

Neither trial was a strict comparison of two different MTX schedules, due to differences in doses of pegaspargase, mercaptopurine, and vincristine between arms, as well as differences in the timing of cranial radiation therapy.

Of note, patients randomized to escalated MTX had two additional doses of pegaspargase. Enhanced asparagine depletion in that arm may have prevented relapse events, the investigators said.

They also said differences in adherence could have played a role, as the cost and time burden of the escalating MTX approach are “substantially less” than the high-dose approach.

The AALL0434 trial also included a second randomization to an addition of five, 6-day cycles of nelarabine versus no nelarabine. Results of that randomization, reported earlier this year, showed that nelarabine improved DFS.

AALL0434 was supported by grants from the National Institutes of Health and by St. Baldrick’s Foundation. Dr. Winter reported relationships with Amgen and Jazz Pharmaceuticals. His coauthors reported relationships with Novo Nordisk, Tandem, Pfizer, Novartis, and TypeZero Technologies, among others.

Any benefit of statins for primary prevention in older adult populations may depend on whether or not type 2 diabetes is present, results of a retrospective cohort study suggest.

Statins had no protective effect overall in the study, which included adults older than 74 years who had no clinically recognized atherosclerotic cardiovascular disease (ASCVD).

In older patients with diabetes, statins were associated with reductions in CVD incidence and all-cause mortality. However, this benefit was substantially reduced in patients 85 years and older, and completely absent in those over 90, study authors said in the BMJ.

“These results do not support the widespread use of statins in old and very old populations, but they do support treatment in those with type 2 diabetes younger than 85 years,” said Rafael Ramos, MD, of the University of Girona, Spain, and his coauthors.

While meta-analyses support statins as primary prevention of CVD in individuals 65 years or older, evidence is lacking on those older than 74 years, according to the investigators.

Accordingly, they conducted the present retrospective cohort study based on data from a Spanish primary care database that included patient records for more than 6 million people. They looked specifically for individuals aged 75 years or older with no history of ASCVD who had at least one visit between July 2006 and December 2007.

They found 46,864 people meeting those criteria, of whom 7,502 (16.0%) had started statin treatment and 7,880 (16.8%) had type 2 diabetes.

With a median follow-up of 7.7 years, statin use had no benefit in reducing ASCVD incidence or all-cause mortality for the entire study population, statistical analyses showed.

In participants with diabetes, however, statins did appear protective, at least in the patients aged 75-84 years, with hazard ratios of 0.76 (95% confidence interval, 0.65-0.89) for CVD and 0.84 (95% CI, 0.75-0.94) for all-cause mortality, Dr. Ramos and his colleagues reported.

The 1-year number needed to treat in this 75-84 age group was 164 for atherosclerotic CVD, and 306 for all-cause mortality, they added.

By contrast, the hazard ratios for patients 85 years and older were 0.82 (95% CI, 0.53-1.26) for atherosclerotic CVD, and 1.05 (95% CI, 0.86-1.28) for all-cause mortality, the investigators reported.

The observed reductions in CVD in individuals with diabetes lost statistical significance at age 85 years when investigators looked at hazard ratios for each year of age. Similarly, reductions in all-cause mortality began to lose statistical significance at age 82 years and “definitively disappeared” in those aged 88 years or older, they said.

The project was supported by grants from the Ministerio de Salud, Spain’s Ministry of Science and Innovation through the Carlos III Health Institute and other entities.

Dr. Ramos and his coauthors declared no support in the previous 3 years from any organization related to, or that might have an interest in, the submitted work. They also declared no other relationships or activities that could appear to have influenced the work.
 

SOURCE: Ramos R et al. BMJ 2018 Sep 5;362:k3359.

Any benefit of statins for primary prevention in older adult populations may depend on whether or not type 2 diabetes is present, results of a retrospective cohort study suggest.

Statins had no protective effect overall in the study, which included adults older than 74 years who had no clinically recognized atherosclerotic cardiovascular disease (ASCVD).

In older patients with diabetes, statins were associated with reductions in CVD incidence and all-cause mortality. However, this benefit was substantially reduced in patients 85 years and older, and completely absent in those over 90, study authors said in the BMJ.

“These results do not support the widespread use of statins in old and very old populations, but they do support treatment in those with type 2 diabetes younger than 85 years,” said Rafael Ramos, MD, of the University of Girona, Spain, and his coauthors.

While meta-analyses support statins as primary prevention of CVD in individuals 65 years or older, evidence is lacking on those older than 74 years, according to the investigators.

Accordingly, they conducted the present retrospective cohort study based on data from a Spanish primary care database that included patient records for more than 6 million people. They looked specifically for individuals aged 75 years or older with no history of ASCVD who had at least one visit between July 2006 and December 2007.

They found 46,864 people meeting those criteria, of whom 7,502 (16.0%) had started statin treatment and 7,880 (16.8%) had type 2 diabetes.

With a median follow-up of 7.7 years, statin use had no benefit in reducing ASCVD incidence or all-cause mortality for the entire study population, statistical analyses showed.

In participants with diabetes, however, statins did appear protective, at least in the patients aged 75-84 years, with hazard ratios of 0.76 (95% confidence interval, 0.65-0.89) for CVD and 0.84 (95% CI, 0.75-0.94) for all-cause mortality, Dr. Ramos and his colleagues reported.

The 1-year number needed to treat in this 75-84 age group was 164 for atherosclerotic CVD, and 306 for all-cause mortality, they added.

By contrast, the hazard ratios for patients 85 years and older were 0.82 (95% CI, 0.53-1.26) for atherosclerotic CVD, and 1.05 (95% CI, 0.86-1.28) for all-cause mortality, the investigators reported.

The observed reductions in CVD in individuals with diabetes lost statistical significance at age 85 years when investigators looked at hazard ratios for each year of age. Similarly, reductions in all-cause mortality began to lose statistical significance at age 82 years and “definitively disappeared” in those aged 88 years or older, they said.

The project was supported by grants from the Ministerio de Salud, Spain’s Ministry of Science and Innovation through the Carlos III Health Institute and other entities.

Dr. Ramos and his coauthors declared no support in the previous 3 years from any organization related to, or that might have an interest in, the submitted work. They also declared no other relationships or activities that could appear to have influenced the work.
 

SOURCE: Ramos R et al. BMJ 2018 Sep 5;362:k3359.

Any benefit of statins for primary prevention in older adult populations may depend on whether or not type 2 diabetes is present, results of a retrospective cohort study suggest.

Statins had no protective effect overall in the study, which included adults older than 74 years who had no clinically recognized atherosclerotic cardiovascular disease (ASCVD).

In older patients with diabetes, statins were associated with reductions in CVD incidence and all-cause mortality. However, this benefit was substantially reduced in patients 85 years and older, and completely absent in those over 90, study authors said in the BMJ.

“These results do not support the widespread use of statins in old and very old populations, but they do support treatment in those with type 2 diabetes younger than 85 years,” said Rafael Ramos, MD, of the University of Girona, Spain, and his coauthors.

While meta-analyses support statins as primary prevention of CVD in individuals 65 years or older, evidence is lacking on those older than 74 years, according to the investigators.

Accordingly, they conducted the present retrospective cohort study based on data from a Spanish primary care database that included patient records for more than 6 million people. They looked specifically for individuals aged 75 years or older with no history of ASCVD who had at least one visit between July 2006 and December 2007.

They found 46,864 people meeting those criteria, of whom 7,502 (16.0%) had started statin treatment and 7,880 (16.8%) had type 2 diabetes.

With a median follow-up of 7.7 years, statin use had no benefit in reducing ASCVD incidence or all-cause mortality for the entire study population, statistical analyses showed.

In participants with diabetes, however, statins did appear protective, at least in the patients aged 75-84 years, with hazard ratios of 0.76 (95% confidence interval, 0.65-0.89) for CVD and 0.84 (95% CI, 0.75-0.94) for all-cause mortality, Dr. Ramos and his colleagues reported.

The 1-year number needed to treat in this 75-84 age group was 164 for atherosclerotic CVD, and 306 for all-cause mortality, they added.

By contrast, the hazard ratios for patients 85 years and older were 0.82 (95% CI, 0.53-1.26) for atherosclerotic CVD, and 1.05 (95% CI, 0.86-1.28) for all-cause mortality, the investigators reported.

The observed reductions in CVD in individuals with diabetes lost statistical significance at age 85 years when investigators looked at hazard ratios for each year of age. Similarly, reductions in all-cause mortality began to lose statistical significance at age 82 years and “definitively disappeared” in those aged 88 years or older, they said.

The project was supported by grants from the Ministerio de Salud, Spain’s Ministry of Science and Innovation through the Carlos III Health Institute and other entities.

Dr. Ramos and his coauthors declared no support in the previous 3 years from any organization related to, or that might have an interest in, the submitted work. They also declared no other relationships or activities that could appear to have influenced the work.
 

SOURCE: Ramos R et al. BMJ 2018 Sep 5;362:k3359.

An escalating methotrexate strategy provided superior survival outcomes compared with high-dose methotrexate in a chemotherapy regimen for children and young adults with T-cell acute lymphoblastic leukemia (T-ALL), results of a large, randomized trial show.

There were also fewer relapses reported for escalating versus high-dose methotrexate in the study, which evaluated the effects of these two intensification strategies in patients receiving an augmented Berlin-Frankfurt-Muenster (ABFM) chemotherapy regimen.

These findings come from a report in the Journal of Clinical Oncology on the Children’s Oncology Group (COG) AALL0434 trial, which to the knowledge of the investigators is the largest T-ALL study ever conducted.

The improved survival outcomes in AALL0434 are the “opposite effect” of what was observed in a parallel trial, AALL0232, showing that high-dose methotrexate was superior to the escalating strategy in B-cell acute lymphoblastic leukemia (B-ALL), the authors reported.

The parallel trial design was in fact used because of the known differences between T-ALL and B-ALL in sensitivity to methotrexate and pegaspargase, according to investigator Stuart S. Winter, MD, of Children’s Minnesota Cancer and Blood Disorders Program, Minneapolis, and his coauthors.

“Although treatment intensification has improved survival for children with ALL, the best timing and sequence of key therapeutic interventions, such as asparaginase and methotrexate, which seem to be particularly important for T-ALL, remain unclear,” Dr. Winter and his colleagues said.

In the AALL0434 study, a total of 1,031 T-ALL patients between 1 and 31 years of age without CNS3 disease or testicular leukemia were randomized to postinduction therapy that included either the so-called Capizzi-style escalating intravenous methotrexate or high-dose methotrexate.

The escalating intravenous regimen was superior to high-dose methotrexate, according to investigators. Respectively, the 5-year rate of disease-free survival was 91.5% versus 85.3% (P = .005) and the 5-year rate of overall survival was 93.7% versus 89.4% (P = .036).

Relapses were observed in 32 patients receiving the escalating regimen, versus 59 for patients receiving high-dose methotrexate.

By contrast, the parallel AALL0232 study of B-ALL patients showed that high-dose methotrexate had superior 5-year event-free survival and overall survival, leading Dr. Winter and his colleagues to speculate on how the findings could be reconciled.

Neither trial was a strict comparison of two different methotrexate schedules, due to differences in doses of pegaspargase, 6-MP, and vincristine between arms, as well as differences in the timing of cranial radiation therapy.

Of note, patients randomized to escalated methotrexate had two additional doses of pegaspargase. As a result, enhanced asparagine depletion in that arm may have also prevented relapse events, the investigators said.

Differences in adherence could also have played a role, as the cost and time burden of the escalated approach are “substantially less” than the high-dose approach, they added.

The AALL0434 trial also included a second randomization to an addition of five, 6-day cycles of nelarabine versus no nelarabine. Results of that randomization, reported earlier this year, showed that nelarabine improved disease-free survival, including a 91% 4-year disease-free survival rate for patients receiving both nelarabine and escalating-dose methotrexate.

The study was supported by grants from the National Institutes of Health and by St. Baldrick’s Foundation. Dr. Winter reported relationships with Amgen and Jazz Pharmaceuticals. Study coauthors reported relationships with Novo Nordisk, Tandem, Pfizer, Novartis, and TypeZero Technologies, among others.

hematologynews@mdedge.com

SOURCE: Winter SS et al. J Clin Oncol. 2018 Aug 23: doi: 10.1200/JCO.2018.77.7250.

An escalating methotrexate strategy provided superior survival outcomes compared with high-dose methotrexate in a chemotherapy regimen for children and young adults with T-cell acute lymphoblastic leukemia (T-ALL), results of a large, randomized trial show.

There were also fewer relapses reported for escalating versus high-dose methotrexate in the study, which evaluated the effects of these two intensification strategies in patients receiving an augmented Berlin-Frankfurt-Muenster (ABFM) chemotherapy regimen.

These findings come from a report in the Journal of Clinical Oncology on the Children’s Oncology Group (COG) AALL0434 trial, which to the knowledge of the investigators is the largest T-ALL study ever conducted.

The improved survival outcomes in AALL0434 are the “opposite effect” of what was observed in a parallel trial, AALL0232, showing that high-dose methotrexate was superior to the escalating strategy in B-cell acute lymphoblastic leukemia (B-ALL), the authors reported.

The parallel trial design was in fact used because of the known differences between T-ALL and B-ALL in sensitivity to methotrexate and pegaspargase, according to investigator Stuart S. Winter, MD, of Children’s Minnesota Cancer and Blood Disorders Program, Minneapolis, and his coauthors.

“Although treatment intensification has improved survival for children with ALL, the best timing and sequence of key therapeutic interventions, such as asparaginase and methotrexate, which seem to be particularly important for T-ALL, remain unclear,” Dr. Winter and his colleagues said.

In the AALL0434 study, a total of 1,031 T-ALL patients between 1 and 31 years of age without CNS3 disease or testicular leukemia were randomized to postinduction therapy that included either the so-called Capizzi-style escalating intravenous methotrexate or high-dose methotrexate.

The escalating intravenous regimen was superior to high-dose methotrexate, according to investigators. Respectively, the 5-year rate of disease-free survival was 91.5% versus 85.3% (P = .005) and the 5-year rate of overall survival was 93.7% versus 89.4% (P = .036).

Relapses were observed in 32 patients receiving the escalating regimen, versus 59 for patients receiving high-dose methotrexate.

By contrast, the parallel AALL0232 study of B-ALL patients showed that high-dose methotrexate had superior 5-year event-free survival and overall survival, leading Dr. Winter and his colleagues to speculate on how the findings could be reconciled.

Neither trial was a strict comparison of two different methotrexate schedules, due to differences in doses of pegaspargase, 6-MP, and vincristine between arms, as well as differences in the timing of cranial radiation therapy.

Of note, patients randomized to escalated methotrexate had two additional doses of pegaspargase. As a result, enhanced asparagine depletion in that arm may have also prevented relapse events, the investigators said.

Differences in adherence could also have played a role, as the cost and time burden of the escalated approach are “substantially less” than the high-dose approach, they added.

The AALL0434 trial also included a second randomization to an addition of five, 6-day cycles of nelarabine versus no nelarabine. Results of that randomization, reported earlier this year, showed that nelarabine improved disease-free survival, including a 91% 4-year disease-free survival rate for patients receiving both nelarabine and escalating-dose methotrexate.

The study was supported by grants from the National Institutes of Health and by St. Baldrick’s Foundation. Dr. Winter reported relationships with Amgen and Jazz Pharmaceuticals. Study coauthors reported relationships with Novo Nordisk, Tandem, Pfizer, Novartis, and TypeZero Technologies, among others.

hematologynews@mdedge.com

SOURCE: Winter SS et al. J Clin Oncol. 2018 Aug 23: doi: 10.1200/JCO.2018.77.7250.

An escalating methotrexate strategy provided superior survival outcomes compared with high-dose methotrexate in a chemotherapy regimen for children and young adults with T-cell acute lymphoblastic leukemia (T-ALL), results of a large, randomized trial show.

There were also fewer relapses reported for escalating versus high-dose methotrexate in the study, which evaluated the effects of these two intensification strategies in patients receiving an augmented Berlin-Frankfurt-Muenster (ABFM) chemotherapy regimen.

These findings come from a report in the Journal of Clinical Oncology on the Children’s Oncology Group (COG) AALL0434 trial, which to the knowledge of the investigators is the largest T-ALL study ever conducted.

The improved survival outcomes in AALL0434 are the “opposite effect” of what was observed in a parallel trial, AALL0232, showing that high-dose methotrexate was superior to the escalating strategy in B-cell acute lymphoblastic leukemia (B-ALL), the authors reported.

The parallel trial design was in fact used because of the known differences between T-ALL and B-ALL in sensitivity to methotrexate and pegaspargase, according to investigator Stuart S. Winter, MD, of Children’s Minnesota Cancer and Blood Disorders Program, Minneapolis, and his coauthors.

“Although treatment intensification has improved survival for children with ALL, the best timing and sequence of key therapeutic interventions, such as asparaginase and methotrexate, which seem to be particularly important for T-ALL, remain unclear,” Dr. Winter and his colleagues said.

In the AALL0434 study, a total of 1,031 T-ALL patients between 1 and 31 years of age without CNS3 disease or testicular leukemia were randomized to postinduction therapy that included either the so-called Capizzi-style escalating intravenous methotrexate or high-dose methotrexate.

The escalating intravenous regimen was superior to high-dose methotrexate, according to investigators. Respectively, the 5-year rate of disease-free survival was 91.5% versus 85.3% (P = .005) and the 5-year rate of overall survival was 93.7% versus 89.4% (P = .036).

Relapses were observed in 32 patients receiving the escalating regimen, versus 59 for patients receiving high-dose methotrexate.

By contrast, the parallel AALL0232 study of B-ALL patients showed that high-dose methotrexate had superior 5-year event-free survival and overall survival, leading Dr. Winter and his colleagues to speculate on how the findings could be reconciled.

Neither trial was a strict comparison of two different methotrexate schedules, due to differences in doses of pegaspargase, 6-MP, and vincristine between arms, as well as differences in the timing of cranial radiation therapy.

Of note, patients randomized to escalated methotrexate had two additional doses of pegaspargase. As a result, enhanced asparagine depletion in that arm may have also prevented relapse events, the investigators said.

Differences in adherence could also have played a role, as the cost and time burden of the escalated approach are “substantially less” than the high-dose approach, they added.

The AALL0434 trial also included a second randomization to an addition of five, 6-day cycles of nelarabine versus no nelarabine. Results of that randomization, reported earlier this year, showed that nelarabine improved disease-free survival, including a 91% 4-year disease-free survival rate for patients receiving both nelarabine and escalating-dose methotrexate.

The study was supported by grants from the National Institutes of Health and by St. Baldrick’s Foundation. Dr. Winter reported relationships with Amgen and Jazz Pharmaceuticals. Study coauthors reported relationships with Novo Nordisk, Tandem, Pfizer, Novartis, and TypeZero Technologies, among others.

hematologynews@mdedge.com

SOURCE: Winter SS et al. J Clin Oncol. 2018 Aug 23: doi: 10.1200/JCO.2018.77.7250.

Some policy responses to the opioid epidemic have immediate, beneficial effects, while others lead to short-term harms that might be offset by long-term health benefits, according to researchers who have mathematically modeled the impact of 11 interventions.

Policies that expand addiction treatment or curb harmful effects of addiction such as overdose and infection were immediately beneficial in the model, with no negative effects on life years (LYs), quality-adjusted life years (QALYs), or addiction deaths, the researchers reported.

In contrast, policies that constrain prescription opioid supply resulted in some benefits, but also short-term harms because of inadequate pain control and users switching to heroin.

However, the modeling study also suggests those harms might be mitigated over the long term as new addictions are averted, according to Allison L. Pitt, a PhD candidate in the department of management science and engineering at Stanford (Calif.) University, and her coauthors.

Combining different interventions had additive benefits in the model, prompting Ms. Pitt and her coauthors to recommend a multifaceted policy approach to curb opioid abuse and reduce addiction deaths.

“No epidemic has ever been averted solely by treating single affected cases,” they wrote in the American Journal of Public Health. “Instead, portfolios of policies will likely be required, including those that prevent addiction, treat addiction, and mitigate its effects.”

In their study, Ms. Pitt and her colleagues projected the impact of 11 policies aimed at curbing opioid addiction and reducing addiction deaths. They used dynamic compartmental modeling, a technique commonly used for evaluating the spread of contagious disease.

This technique is appropriate for studying the opioid epidemic, because it allows for dynamic modeling of addiction incidence that reflects a changing number of prescription holders, the authors said in their report, which focused on projected outcomes of various interventions at 5 and 10 years.

None of the policies substantially reduced opioid-related deaths in 5-year outcomes projections, they found. Increasing availability of naloxone averted 4% of addiction deaths, the highest reduction of any intervention over that time period.

However, interventions focused on providing services for people with addictions did generally provide uniform benefits over the 5-year horizon: “Naloxone availability, needle exchange, medication-assisted treatment, and psychosocial treatment policies generate gains in LYs and QALYs and reduce deaths, without harming any group,” Ms. Pitt and her coauthors said.

Interventions that reduced opioid supply, such as excess opioid disposal and reduced prescribing for transitioning pain, increased LYs and QALYs while decreasing total addiction deaths over 5 years. However, the investigators said, those benefits were partly offset by increases in heroin-related deaths.

Drug rescheduling was associated with a 45.6% increase in heroin-related deaths over 5 years in the model, the highest percentage increase of any intervention in the published data.

Over the 10-year horizon, addiction deaths continued to decrease proportionally for naloxone availability and needle-exchange policies, authors said. By comparison, policies focused on opioid supply, such as excess opioid disposal and reduced prescribing for transitioning pain, averted substantially more deaths over 10 years than would be expected, compared with the 5-year results, investigators said.

Acute pain prescribing, which increased opioid-related deaths over 5 years in the model, was associated with a decrease in opioid-related deaths over 10 years, they added.

The report coauthors were Keith Humphreys, PhD, of Stanford’s department of psychiatry and behavioral sciences, and Margaret L. Brandeau, PhD, of the university’s department of management science and engineering.

The coauthors cited several limitations. One is that the opioid epidemic is changing in unpredictable ways. Therefore, numerous assumptions about the epidemic were made based on the opinions of clinicians and scientists.

The study was supported by a grant from the National Institute on Drug Abuse. Dr. Humphreys reported support through a Senior Career Research Scientist award from the VA Health Services Research and Development Service.

SOURCE: Pitt AL et al. Am J Public Health. 2018 Aug 23. doi: 10.2105/AJPH.2018.304590.

Some policy responses to the opioid epidemic have immediate, beneficial effects, while others lead to short-term harms that might be offset by long-term health benefits, according to researchers who have mathematically modeled the impact of 11 interventions.

Policies that expand addiction treatment or curb harmful effects of addiction such as overdose and infection were immediately beneficial in the model, with no negative effects on life years (LYs), quality-adjusted life years (QALYs), or addiction deaths, the researchers reported.

In contrast, policies that constrain prescription opioid supply resulted in some benefits, but also short-term harms because of inadequate pain control and users switching to heroin.

However, the modeling study also suggests those harms might be mitigated over the long term as new addictions are averted, according to Allison L. Pitt, a PhD candidate in the department of management science and engineering at Stanford (Calif.) University, and her coauthors.

Combining different interventions had additive benefits in the model, prompting Ms. Pitt and her coauthors to recommend a multifaceted policy approach to curb opioid abuse and reduce addiction deaths.

“No epidemic has ever been averted solely by treating single affected cases,” they wrote in the American Journal of Public Health. “Instead, portfolios of policies will likely be required, including those that prevent addiction, treat addiction, and mitigate its effects.”

In their study, Ms. Pitt and her colleagues projected the impact of 11 policies aimed at curbing opioid addiction and reducing addiction deaths. They used dynamic compartmental modeling, a technique commonly used for evaluating the spread of contagious disease.

This technique is appropriate for studying the opioid epidemic, because it allows for dynamic modeling of addiction incidence that reflects a changing number of prescription holders, the authors said in their report, which focused on projected outcomes of various interventions at 5 and 10 years.

None of the policies substantially reduced opioid-related deaths in 5-year outcomes projections, they found. Increasing availability of naloxone averted 4% of addiction deaths, the highest reduction of any intervention over that time period.

However, interventions focused on providing services for people with addictions did generally provide uniform benefits over the 5-year horizon: “Naloxone availability, needle exchange, medication-assisted treatment, and psychosocial treatment policies generate gains in LYs and QALYs and reduce deaths, without harming any group,” Ms. Pitt and her coauthors said.

Interventions that reduced opioid supply, such as excess opioid disposal and reduced prescribing for transitioning pain, increased LYs and QALYs while decreasing total addiction deaths over 5 years. However, the investigators said, those benefits were partly offset by increases in heroin-related deaths.

Drug rescheduling was associated with a 45.6% increase in heroin-related deaths over 5 years in the model, the highest percentage increase of any intervention in the published data.

Over the 10-year horizon, addiction deaths continued to decrease proportionally for naloxone availability and needle-exchange policies, authors said. By comparison, policies focused on opioid supply, such as excess opioid disposal and reduced prescribing for transitioning pain, averted substantially more deaths over 10 years than would be expected, compared with the 5-year results, investigators said.

Acute pain prescribing, which increased opioid-related deaths over 5 years in the model, was associated with a decrease in opioid-related deaths over 10 years, they added.

The report coauthors were Keith Humphreys, PhD, of Stanford’s department of psychiatry and behavioral sciences, and Margaret L. Brandeau, PhD, of the university’s department of management science and engineering.

The coauthors cited several limitations. One is that the opioid epidemic is changing in unpredictable ways. Therefore, numerous assumptions about the epidemic were made based on the opinions of clinicians and scientists.

The study was supported by a grant from the National Institute on Drug Abuse. Dr. Humphreys reported support through a Senior Career Research Scientist award from the VA Health Services Research and Development Service.

SOURCE: Pitt AL et al. Am J Public Health. 2018 Aug 23. doi: 10.2105/AJPH.2018.304590.

Some policy responses to the opioid epidemic have immediate, beneficial effects, while others lead to short-term harms that might be offset by long-term health benefits, according to researchers who have mathematically modeled the impact of 11 interventions.

Policies that expand addiction treatment or curb harmful effects of addiction such as overdose and infection were immediately beneficial in the model, with no negative effects on life years (LYs), quality-adjusted life years (QALYs), or addiction deaths, the researchers reported.

In contrast, policies that constrain prescription opioid supply resulted in some benefits, but also short-term harms because of inadequate pain control and users switching to heroin.

However, the modeling study also suggests those harms might be mitigated over the long term as new addictions are averted, according to Allison L. Pitt, a PhD candidate in the department of management science and engineering at Stanford (Calif.) University, and her coauthors.

Combining different interventions had additive benefits in the model, prompting Ms. Pitt and her coauthors to recommend a multifaceted policy approach to curb opioid abuse and reduce addiction deaths.

“No epidemic has ever been averted solely by treating single affected cases,” they wrote in the American Journal of Public Health. “Instead, portfolios of policies will likely be required, including those that prevent addiction, treat addiction, and mitigate its effects.”

In their study, Ms. Pitt and her colleagues projected the impact of 11 policies aimed at curbing opioid addiction and reducing addiction deaths. They used dynamic compartmental modeling, a technique commonly used for evaluating the spread of contagious disease.

This technique is appropriate for studying the opioid epidemic, because it allows for dynamic modeling of addiction incidence that reflects a changing number of prescription holders, the authors said in their report, which focused on projected outcomes of various interventions at 5 and 10 years.

None of the policies substantially reduced opioid-related deaths in 5-year outcomes projections, they found. Increasing availability of naloxone averted 4% of addiction deaths, the highest reduction of any intervention over that time period.

However, interventions focused on providing services for people with addictions did generally provide uniform benefits over the 5-year horizon: “Naloxone availability, needle exchange, medication-assisted treatment, and psychosocial treatment policies generate gains in LYs and QALYs and reduce deaths, without harming any group,” Ms. Pitt and her coauthors said.

Interventions that reduced opioid supply, such as excess opioid disposal and reduced prescribing for transitioning pain, increased LYs and QALYs while decreasing total addiction deaths over 5 years. However, the investigators said, those benefits were partly offset by increases in heroin-related deaths.

Drug rescheduling was associated with a 45.6% increase in heroin-related deaths over 5 years in the model, the highest percentage increase of any intervention in the published data.

Over the 10-year horizon, addiction deaths continued to decrease proportionally for naloxone availability and needle-exchange policies, authors said. By comparison, policies focused on opioid supply, such as excess opioid disposal and reduced prescribing for transitioning pain, averted substantially more deaths over 10 years than would be expected, compared with the 5-year results, investigators said.

Acute pain prescribing, which increased opioid-related deaths over 5 years in the model, was associated with a decrease in opioid-related deaths over 10 years, they added.

The report coauthors were Keith Humphreys, PhD, of Stanford’s department of psychiatry and behavioral sciences, and Margaret L. Brandeau, PhD, of the university’s department of management science and engineering.

The coauthors cited several limitations. One is that the opioid epidemic is changing in unpredictable ways. Therefore, numerous assumptions about the epidemic were made based on the opinions of clinicians and scientists.

The study was supported by a grant from the National Institute on Drug Abuse. Dr. Humphreys reported support through a Senior Career Research Scientist award from the VA Health Services Research and Development Service.

SOURCE: Pitt AL et al. Am J Public Health. 2018 Aug 23. doi: 10.2105/AJPH.2018.304590.

Expression of programmed death-1 (PD1) mRNA may predict outcomes after anti-PD1 therapy across cancer types, according to investigators.

High levels of PD1 mRNA were significantly associated with response to anti-PD1 monotherapy, investigators found in an analysis of tumor samples from 117 patients with advanced cancers who had received either nivolumab or pembrolizumab.

Further validation of PD1 mRNA is warranted to help select patients who might benefit from an anti-PD1 treatment strategy, wrote investigator Aleix Prat, MD, PhD, of Hospital Clínic of Barcelona, and his coinvestigators.

“Identification of reproducible biomarkers that can be applied to predict benefit of anti-PD1 monotherapy might be of clinical value,” Dr. Prat and his coinvestigators note. The report is in Annals of Oncology.

Previous studies support use of PDL1 expression by immunohistochemistry as a biomarker for pembrolizumab in non–small-cell lung cancer; however, that biomarker has some technical limitations, and has not been predictive in other cancer types and with other anti-PD1 drugs including nivolumab, Dr. Prat and his coinvestigators said.

The 117 tumor samples evaluated for PD1 mRNA expression comprised 59 advanced melanomas, 32 non–small-cell lung cancers, 14 renal cell cancers, and 12 other tumors, according to the report. Sixty-two of the patients had been treated with pembrolizumab, and 55 received nivolumab.

About one-quarter of the samples (28.2%) were classified as “PD1-high” with a preestablished cutoff value developed by Dr. Prat and his coinvestigators.

The overall response rate was 51.5% for the patients who had PD1-high tumors, versus 23.8% for the remaining tumors (P less than .001). Those non-PD1-high tumors, when grouped as PD1-intermediate and PD1-low, had overall response rates of 26.6% and 15.0%, respectively.

Median progression-free survival was 8.17 months for PD1-high tumors and 3.18 months for the rest of the tumors (P = .011), the report shows. Similarly, overall survival was a median of 23.4 months for PD1-high tumors and 14.9 months for the rest (P = .330).

Dr. Prat and his colleagues detailed earlier investigations validating PD1 mRNA as a biomarker, including an analysis of PD1 and immune-related gene expression in 10,078 samples from 34 cancer types in The Cancer Genome Atlas.

In that analysis, PD1 was strongly correlated with a group of 30 genes that were “significantly enriched” in biological processes including CD8-T-cell activation, the investigators said.

Moreover, high levels of PD1 mRNA expression were strongly correlated with overall response rates reported in the literature for anti-PD1 monotherapy, they added.

They also reported results of an analysis they used to develop the PD1-high cutoff value. That analysis was based on PD1 mRNA expression in 773 tumor samples across 17 tumor types.

“Our results are consistent with the hypothesis that identification of a preexisting and stable adaptive immune response using PD1 mRNA expression predicts outcome across cancer-types following anti-PD1 monotherapy,” the researchers wrote.

The work was partially sponsored by Instituto de Salud Carlos III, Spanish Society of Medical Oncology, Banco Bilbao Vizcaya Argentaria Foundation, Pas a Pas, Save the Mama, and the Breast Cancer Research Foundation. Dr. Prat disclosed an advisory role with Nanostring Technologies.

SOURCE: Paré L et al. Ann Oncol. 2018 Aug 27. doi: 10.1093/annonc/mdy335.

Expression of programmed death-1 (PD1) mRNA may predict outcomes after anti-PD1 therapy across cancer types, according to investigators.

High levels of PD1 mRNA were significantly associated with response to anti-PD1 monotherapy, investigators found in an analysis of tumor samples from 117 patients with advanced cancers who had received either nivolumab or pembrolizumab.

Further validation of PD1 mRNA is warranted to help select patients who might benefit from an anti-PD1 treatment strategy, wrote investigator Aleix Prat, MD, PhD, of Hospital Clínic of Barcelona, and his coinvestigators.

“Identification of reproducible biomarkers that can be applied to predict benefit of anti-PD1 monotherapy might be of clinical value,” Dr. Prat and his coinvestigators note. The report is in Annals of Oncology.

Previous studies support use of PDL1 expression by immunohistochemistry as a biomarker for pembrolizumab in non–small-cell lung cancer; however, that biomarker has some technical limitations, and has not been predictive in other cancer types and with other anti-PD1 drugs including nivolumab, Dr. Prat and his coinvestigators said.

The 117 tumor samples evaluated for PD1 mRNA expression comprised 59 advanced melanomas, 32 non–small-cell lung cancers, 14 renal cell cancers, and 12 other tumors, according to the report. Sixty-two of the patients had been treated with pembrolizumab, and 55 received nivolumab.

About one-quarter of the samples (28.2%) were classified as “PD1-high” with a preestablished cutoff value developed by Dr. Prat and his coinvestigators.

The overall response rate was 51.5% for the patients who had PD1-high tumors, versus 23.8% for the remaining tumors (P less than .001). Those non-PD1-high tumors, when grouped as PD1-intermediate and PD1-low, had overall response rates of 26.6% and 15.0%, respectively.

Median progression-free survival was 8.17 months for PD1-high tumors and 3.18 months for the rest of the tumors (P = .011), the report shows. Similarly, overall survival was a median of 23.4 months for PD1-high tumors and 14.9 months for the rest (P = .330).

Dr. Prat and his colleagues detailed earlier investigations validating PD1 mRNA as a biomarker, including an analysis of PD1 and immune-related gene expression in 10,078 samples from 34 cancer types in The Cancer Genome Atlas.

In that analysis, PD1 was strongly correlated with a group of 30 genes that were “significantly enriched” in biological processes including CD8-T-cell activation, the investigators said.

Moreover, high levels of PD1 mRNA expression were strongly correlated with overall response rates reported in the literature for anti-PD1 monotherapy, they added.

They also reported results of an analysis they used to develop the PD1-high cutoff value. That analysis was based on PD1 mRNA expression in 773 tumor samples across 17 tumor types.

“Our results are consistent with the hypothesis that identification of a preexisting and stable adaptive immune response using PD1 mRNA expression predicts outcome across cancer-types following anti-PD1 monotherapy,” the researchers wrote.

The work was partially sponsored by Instituto de Salud Carlos III, Spanish Society of Medical Oncology, Banco Bilbao Vizcaya Argentaria Foundation, Pas a Pas, Save the Mama, and the Breast Cancer Research Foundation. Dr. Prat disclosed an advisory role with Nanostring Technologies.

SOURCE: Paré L et al. Ann Oncol. 2018 Aug 27. doi: 10.1093/annonc/mdy335.

Expression of programmed death-1 (PD1) mRNA may predict outcomes after anti-PD1 therapy across cancer types, according to investigators.

High levels of PD1 mRNA were significantly associated with response to anti-PD1 monotherapy, investigators found in an analysis of tumor samples from 117 patients with advanced cancers who had received either nivolumab or pembrolizumab.

Further validation of PD1 mRNA is warranted to help select patients who might benefit from an anti-PD1 treatment strategy, wrote investigator Aleix Prat, MD, PhD, of Hospital Clínic of Barcelona, and his coinvestigators.

“Identification of reproducible biomarkers that can be applied to predict benefit of anti-PD1 monotherapy might be of clinical value,” Dr. Prat and his coinvestigators note. The report is in Annals of Oncology.

Previous studies support use of PDL1 expression by immunohistochemistry as a biomarker for pembrolizumab in non–small-cell lung cancer; however, that biomarker has some technical limitations, and has not been predictive in other cancer types and with other anti-PD1 drugs including nivolumab, Dr. Prat and his coinvestigators said.

The 117 tumor samples evaluated for PD1 mRNA expression comprised 59 advanced melanomas, 32 non–small-cell lung cancers, 14 renal cell cancers, and 12 other tumors, according to the report. Sixty-two of the patients had been treated with pembrolizumab, and 55 received nivolumab.

About one-quarter of the samples (28.2%) were classified as “PD1-high” with a preestablished cutoff value developed by Dr. Prat and his coinvestigators.

The overall response rate was 51.5% for the patients who had PD1-high tumors, versus 23.8% for the remaining tumors (P less than .001). Those non-PD1-high tumors, when grouped as PD1-intermediate and PD1-low, had overall response rates of 26.6% and 15.0%, respectively.

Median progression-free survival was 8.17 months for PD1-high tumors and 3.18 months for the rest of the tumors (P = .011), the report shows. Similarly, overall survival was a median of 23.4 months for PD1-high tumors and 14.9 months for the rest (P = .330).

Dr. Prat and his colleagues detailed earlier investigations validating PD1 mRNA as a biomarker, including an analysis of PD1 and immune-related gene expression in 10,078 samples from 34 cancer types in The Cancer Genome Atlas.

In that analysis, PD1 was strongly correlated with a group of 30 genes that were “significantly enriched” in biological processes including CD8-T-cell activation, the investigators said.

Moreover, high levels of PD1 mRNA expression were strongly correlated with overall response rates reported in the literature for anti-PD1 monotherapy, they added.

They also reported results of an analysis they used to develop the PD1-high cutoff value. That analysis was based on PD1 mRNA expression in 773 tumor samples across 17 tumor types.

“Our results are consistent with the hypothesis that identification of a preexisting and stable adaptive immune response using PD1 mRNA expression predicts outcome across cancer-types following anti-PD1 monotherapy,” the researchers wrote.

The work was partially sponsored by Instituto de Salud Carlos III, Spanish Society of Medical Oncology, Banco Bilbao Vizcaya Argentaria Foundation, Pas a Pas, Save the Mama, and the Breast Cancer Research Foundation. Dr. Prat disclosed an advisory role with Nanostring Technologies.

SOURCE: Paré L et al. Ann Oncol. 2018 Aug 27. doi: 10.1093/annonc/mdy335.

A novel method for detection of translocations appears to be superior to conventional molecular assays in the evaluation of bone and soft tissue tumor samples, according to researchers.

The technique of anchored multiplex polymerase chain reaction (AMP)–based targeted next-generation sequencing (NGS) had a failure rate of 14% but, nonetheless, worked favorably when compared with conventional techniques, which were associated with several false positives in this study, the researchers reported in the Journal of Molecular Diagnostics.

Two new fusion partners for the USP6 gene were found using AMP-based targeted NGS in this study, which thus contributed to the “further unraveling of the molecular landscape” for these tumors, added corresponding author Judith V.M.G. Bovée, MD, PhD, of the department of pathology at Leiden (the Netherlands) University Medical Center and her colleagues.

While the genetics of bone and soft tissue tumors have diagnostic value in clinical practice, standard fluorescence in situ hybridization (FISH) and reverse transcriptase PCR are associated with several drawbacks, such as a high false negative rate in the case of FISH, Dr. Bovée and her coauthors wrote.

Accordingly, the researchers evaluated the applicability of a targeted sequencing assay (Archer FusionPlex Sarcoma kit, which was developed by ArcherDX) aimed at 26 genes relevant to bone and soft tissue tumor diagnostics.

Besides allowing for assessment of multiple target genes in a single assay, this technique circumvents the need to know both fusion partners for translocation detection, which opens up the possibility of identifying novel or rare fusion partners, investigators noted.

AMP-based targeted NGS was used to evaluate 81 bone and soft tissue tumor samples, and of those, 48 cases showed a fusion. For the remaining 33 cases in which no fusion was detected, 22 were considered truly negative because samples met all criteria for good quality, while the remaining 11 (14%) were considered not reliable because of insufficient quality, investigators reported.

The samples were also evaluated through use of FISH, reverse transcriptase PCR, or both in 58 cases and use of immunohistochemistry in 16 cases; for the remaining seven cases, no assay or immunohistochemistry could be applied because of a lack of availability, according to investigators.

Among the 48 entities that were fusion-positive according to AMP-based targeted NGS, 29 were validated using standard molecular assays, and of those, 25 had concordant results. Further analysis of the four discordant cases with a third independent technique confirmed the AMP-based targeted NGS findings, according to the published report.

Among the 22 fusion-negative high-quality samples, 19 were validated using FISH, and one case was found to be discordant; however, despite use of a third independent technique, this discrepancy could not be resolved, investigators said.

The AMP-based targeted NGS technique identified COL1A1 and SEC31A as novel fusion partners for USP6 in two cases of nodular fasciitis. Those fusion partners had been previously described in aneurysmal bone cysts, according to investigators.

Despite the promising results for the novel assay, conventional methods were sufficient in this study to confirm translocations in straightforward cases and ordinary rearrangements, according to the investigators.

“Both reverse transcription PCR and FISH are not only quick and easy to conduct but are also of low cost and high analytical validity and accuracy, which make them attractive methods,” they wrote.

The work by Dr. Bovée and her colleagues was supported by Leiden University Medical Center. The department of pathology and the department of cell and chemical biology at the medical center receive royalty payments from Kreatech/Leica, which provided a COL1A1/PDGFB fusion probe used in the research.

SOURCE: Lam SW et al. J Mol Diagn. 2018 Aug 20;20(5):653-63.

A novel method for detection of translocations appears to be superior to conventional molecular assays in the evaluation of bone and soft tissue tumor samples, according to researchers.

The technique of anchored multiplex polymerase chain reaction (AMP)–based targeted next-generation sequencing (NGS) had a failure rate of 14% but, nonetheless, worked favorably when compared with conventional techniques, which were associated with several false positives in this study, the researchers reported in the Journal of Molecular Diagnostics.

Two new fusion partners for the USP6 gene were found using AMP-based targeted NGS in this study, which thus contributed to the “further unraveling of the molecular landscape” for these tumors, added corresponding author Judith V.M.G. Bovée, MD, PhD, of the department of pathology at Leiden (the Netherlands) University Medical Center and her colleagues.

While the genetics of bone and soft tissue tumors have diagnostic value in clinical practice, standard fluorescence in situ hybridization (FISH) and reverse transcriptase PCR are associated with several drawbacks, such as a high false negative rate in the case of FISH, Dr. Bovée and her coauthors wrote.

Accordingly, the researchers evaluated the applicability of a targeted sequencing assay (Archer FusionPlex Sarcoma kit, which was developed by ArcherDX) aimed at 26 genes relevant to bone and soft tissue tumor diagnostics.

Besides allowing for assessment of multiple target genes in a single assay, this technique circumvents the need to know both fusion partners for translocation detection, which opens up the possibility of identifying novel or rare fusion partners, investigators noted.

AMP-based targeted NGS was used to evaluate 81 bone and soft tissue tumor samples, and of those, 48 cases showed a fusion. For the remaining 33 cases in which no fusion was detected, 22 were considered truly negative because samples met all criteria for good quality, while the remaining 11 (14%) were considered not reliable because of insufficient quality, investigators reported.

The samples were also evaluated through use of FISH, reverse transcriptase PCR, or both in 58 cases and use of immunohistochemistry in 16 cases; for the remaining seven cases, no assay or immunohistochemistry could be applied because of a lack of availability, according to investigators.

Among the 48 entities that were fusion-positive according to AMP-based targeted NGS, 29 were validated using standard molecular assays, and of those, 25 had concordant results. Further analysis of the four discordant cases with a third independent technique confirmed the AMP-based targeted NGS findings, according to the published report.

Among the 22 fusion-negative high-quality samples, 19 were validated using FISH, and one case was found to be discordant; however, despite use of a third independent technique, this discrepancy could not be resolved, investigators said.

The AMP-based targeted NGS technique identified COL1A1 and SEC31A as novel fusion partners for USP6 in two cases of nodular fasciitis. Those fusion partners had been previously described in aneurysmal bone cysts, according to investigators.

Despite the promising results for the novel assay, conventional methods were sufficient in this study to confirm translocations in straightforward cases and ordinary rearrangements, according to the investigators.

“Both reverse transcription PCR and FISH are not only quick and easy to conduct but are also of low cost and high analytical validity and accuracy, which make them attractive methods,” they wrote.

The work by Dr. Bovée and her colleagues was supported by Leiden University Medical Center. The department of pathology and the department of cell and chemical biology at the medical center receive royalty payments from Kreatech/Leica, which provided a COL1A1/PDGFB fusion probe used in the research.

SOURCE: Lam SW et al. J Mol Diagn. 2018 Aug 20;20(5):653-63.

A novel method for detection of translocations appears to be superior to conventional molecular assays in the evaluation of bone and soft tissue tumor samples, according to researchers.

The technique of anchored multiplex polymerase chain reaction (AMP)–based targeted next-generation sequencing (NGS) had a failure rate of 14% but, nonetheless, worked favorably when compared with conventional techniques, which were associated with several false positives in this study, the researchers reported in the Journal of Molecular Diagnostics.

Two new fusion partners for the USP6 gene were found using AMP-based targeted NGS in this study, which thus contributed to the “further unraveling of the molecular landscape” for these tumors, added corresponding author Judith V.M.G. Bovée, MD, PhD, of the department of pathology at Leiden (the Netherlands) University Medical Center and her colleagues.

While the genetics of bone and soft tissue tumors have diagnostic value in clinical practice, standard fluorescence in situ hybridization (FISH) and reverse transcriptase PCR are associated with several drawbacks, such as a high false negative rate in the case of FISH, Dr. Bovée and her coauthors wrote.

Accordingly, the researchers evaluated the applicability of a targeted sequencing assay (Archer FusionPlex Sarcoma kit, which was developed by ArcherDX) aimed at 26 genes relevant to bone and soft tissue tumor diagnostics.

Besides allowing for assessment of multiple target genes in a single assay, this technique circumvents the need to know both fusion partners for translocation detection, which opens up the possibility of identifying novel or rare fusion partners, investigators noted.

AMP-based targeted NGS was used to evaluate 81 bone and soft tissue tumor samples, and of those, 48 cases showed a fusion. For the remaining 33 cases in which no fusion was detected, 22 were considered truly negative because samples met all criteria for good quality, while the remaining 11 (14%) were considered not reliable because of insufficient quality, investigators reported.

The samples were also evaluated through use of FISH, reverse transcriptase PCR, or both in 58 cases and use of immunohistochemistry in 16 cases; for the remaining seven cases, no assay or immunohistochemistry could be applied because of a lack of availability, according to investigators.

Among the 48 entities that were fusion-positive according to AMP-based targeted NGS, 29 were validated using standard molecular assays, and of those, 25 had concordant results. Further analysis of the four discordant cases with a third independent technique confirmed the AMP-based targeted NGS findings, according to the published report.

Among the 22 fusion-negative high-quality samples, 19 were validated using FISH, and one case was found to be discordant; however, despite use of a third independent technique, this discrepancy could not be resolved, investigators said.

The AMP-based targeted NGS technique identified COL1A1 and SEC31A as novel fusion partners for USP6 in two cases of nodular fasciitis. Those fusion partners had been previously described in aneurysmal bone cysts, according to investigators.

Despite the promising results for the novel assay, conventional methods were sufficient in this study to confirm translocations in straightforward cases and ordinary rearrangements, according to the investigators.

“Both reverse transcription PCR and FISH are not only quick and easy to conduct but are also of low cost and high analytical validity and accuracy, which make them attractive methods,” they wrote.

The work by Dr. Bovée and her colleagues was supported by Leiden University Medical Center. The department of pathology and the department of cell and chemical biology at the medical center receive royalty payments from Kreatech/Leica, which provided a COL1A1/PDGFB fusion probe used in the research.

SOURCE: Lam SW et al. J Mol Diagn. 2018 Aug 20;20(5):653-63.

A proactive side-effect management strategy enabled many patients with high-risk renal cell carcinoma (RCC) to stay on adjuvant sunitinib therapy in a recent clinical trial, researchers report.

With dose interruptions, dose reductions, and supportive medical therapy, adverse events on adjuvant sunitinib were predictable, manageable, and reversible, according to their report on the S-TRAC (Sunitinib as Adjuvant Treatment for High-Risk Renal Cell Carcinoma Following Nephrectomy) trial.

Patients did report reduced health-related quality of life, but with the exception of diarrhea and loss of appetite, those changes were generally not clinically significant, the investigators wrote. The report is in Annals of Oncology.

The safety profile for sunitinib was acceptable in adjuvant RCC treatment in S-TRAC, with no safety signals observed, said Michael Staehler, MD, PhD, department of urology, Ludwig Maximilian University of Munich, and his coauthors.

“It is likely proactive management contributed to preservation of global health status and quality of life, and alleviation of treatment-related symptoms, thereby enabling patients to remain on effective adjuvant therapy,” Dr. Staehler and his coauthors said.

Sunitinib is approved by the Food and Drug Administration for adjuvant treatment of patients at high risk of recurrent RCC after nephrectomy. That was based in part on previously reported results of the phase 3 S-TRAC study, which showed a 24% reduction in risk of a disease-free survival event versus placebo.

For the 306 patients randomized to sunitinib, 71% stayed on treatment for at least 8 months, reaching cycle 6 of therapy, while 56% finished the full year of treatment, Dr. Staehler and his coauthors said in this new report on S-TRAC focused on adverse events and patient-reported outcomes.

The most common adverse events in the sunitinib arm of S-TRAC included diarrhea in 56.9%, versus 21.4% in the placebo arm, palmar-plantar erythrodysesthesia (PPE) in 50.3% versus 10.2% for placebo, and hypertension in 36.9% versus 11.8% for placebo. The frequency of serious adverse events was similar between arms, according to the investigators, at 21.9% for sunitinib and 17.1% for placebo.

Adverse events were the most common reason for dose reduction, cited in 34.6% of cases, and for dose interruption, reported in 46.4%, they said.

Treatment discontinuations due to adverse events occurred in 28.1%, usually because of PPE.

The S-TRAC study investigators used the EORTC QLQ-C30 instrument to evaluate patient experience during treatment.

That evaluation included an analysis of global health status/quality of life score that favored placebo, with a mean difference in the overall means of –4.76. Although statistically significant (P greater than or equal to .0001), the point estimate of the difference was below the commonly accepted threshold that would indicate clinically meaningful deterioration, investigators said.

Similar patterns that were statistically significant but not clinically meaningful were seen for symptoms including fatigue and pain. However, patient-reported scores for diarrhea and loss of appetite did reach the level of a clinically meaningful difference.

But only one patient permanently discontinued sunitinib because of diarrhea, and none permanently discontinued because of loss of appetite, Dr. Staehler and his coauthors noted.

The work was sponsored by Pfizer. Dr. Staehler reported honoraria, consulting fees, and research grants from Pfizer, Bayer, GSK, Roche, BMS, Novartis, Exelixis, and AVEO. Coauthors reported disclosures related to Merck, Sanofi, Astellas, Celldex, Acerta, Janssen, and others.

SOURCE: Staehler M et al. Ann Oncol. 2018 Aug 23. doi: 10.1093/annonc/mdy329.

A proactive side-effect management strategy enabled many patients with high-risk renal cell carcinoma (RCC) to stay on adjuvant sunitinib therapy in a recent clinical trial, researchers report.

With dose interruptions, dose reductions, and supportive medical therapy, adverse events on adjuvant sunitinib were predictable, manageable, and reversible, according to their report on the S-TRAC (Sunitinib as Adjuvant Treatment for High-Risk Renal Cell Carcinoma Following Nephrectomy) trial.

Patients did report reduced health-related quality of life, but with the exception of diarrhea and loss of appetite, those changes were generally not clinically significant, the investigators wrote. The report is in Annals of Oncology.

The safety profile for sunitinib was acceptable in adjuvant RCC treatment in S-TRAC, with no safety signals observed, said Michael Staehler, MD, PhD, department of urology, Ludwig Maximilian University of Munich, and his coauthors.

“It is likely proactive management contributed to preservation of global health status and quality of life, and alleviation of treatment-related symptoms, thereby enabling patients to remain on effective adjuvant therapy,” Dr. Staehler and his coauthors said.

Sunitinib is approved by the Food and Drug Administration for adjuvant treatment of patients at high risk of recurrent RCC after nephrectomy. That was based in part on previously reported results of the phase 3 S-TRAC study, which showed a 24% reduction in risk of a disease-free survival event versus placebo.

For the 306 patients randomized to sunitinib, 71% stayed on treatment for at least 8 months, reaching cycle 6 of therapy, while 56% finished the full year of treatment, Dr. Staehler and his coauthors said in this new report on S-TRAC focused on adverse events and patient-reported outcomes.

The most common adverse events in the sunitinib arm of S-TRAC included diarrhea in 56.9%, versus 21.4% in the placebo arm, palmar-plantar erythrodysesthesia (PPE) in 50.3% versus 10.2% for placebo, and hypertension in 36.9% versus 11.8% for placebo. The frequency of serious adverse events was similar between arms, according to the investigators, at 21.9% for sunitinib and 17.1% for placebo.

Adverse events were the most common reason for dose reduction, cited in 34.6% of cases, and for dose interruption, reported in 46.4%, they said.

Treatment discontinuations due to adverse events occurred in 28.1%, usually because of PPE.

The S-TRAC study investigators used the EORTC QLQ-C30 instrument to evaluate patient experience during treatment.

That evaluation included an analysis of global health status/quality of life score that favored placebo, with a mean difference in the overall means of –4.76. Although statistically significant (P greater than or equal to .0001), the point estimate of the difference was below the commonly accepted threshold that would indicate clinically meaningful deterioration, investigators said.

Similar patterns that were statistically significant but not clinically meaningful were seen for symptoms including fatigue and pain. However, patient-reported scores for diarrhea and loss of appetite did reach the level of a clinically meaningful difference.

But only one patient permanently discontinued sunitinib because of diarrhea, and none permanently discontinued because of loss of appetite, Dr. Staehler and his coauthors noted.

The work was sponsored by Pfizer. Dr. Staehler reported honoraria, consulting fees, and research grants from Pfizer, Bayer, GSK, Roche, BMS, Novartis, Exelixis, and AVEO. Coauthors reported disclosures related to Merck, Sanofi, Astellas, Celldex, Acerta, Janssen, and others.

SOURCE: Staehler M et al. Ann Oncol. 2018 Aug 23. doi: 10.1093/annonc/mdy329.

A proactive side-effect management strategy enabled many patients with high-risk renal cell carcinoma (RCC) to stay on adjuvant sunitinib therapy in a recent clinical trial, researchers report.

With dose interruptions, dose reductions, and supportive medical therapy, adverse events on adjuvant sunitinib were predictable, manageable, and reversible, according to their report on the S-TRAC (Sunitinib as Adjuvant Treatment for High-Risk Renal Cell Carcinoma Following Nephrectomy) trial.

Patients did report reduced health-related quality of life, but with the exception of diarrhea and loss of appetite, those changes were generally not clinically significant, the investigators wrote. The report is in Annals of Oncology.

The safety profile for sunitinib was acceptable in adjuvant RCC treatment in S-TRAC, with no safety signals observed, said Michael Staehler, MD, PhD, department of urology, Ludwig Maximilian University of Munich, and his coauthors.

“It is likely proactive management contributed to preservation of global health status and quality of life, and alleviation of treatment-related symptoms, thereby enabling patients to remain on effective adjuvant therapy,” Dr. Staehler and his coauthors said.

Sunitinib is approved by the Food and Drug Administration for adjuvant treatment of patients at high risk of recurrent RCC after nephrectomy. That was based in part on previously reported results of the phase 3 S-TRAC study, which showed a 24% reduction in risk of a disease-free survival event versus placebo.

For the 306 patients randomized to sunitinib, 71% stayed on treatment for at least 8 months, reaching cycle 6 of therapy, while 56% finished the full year of treatment, Dr. Staehler and his coauthors said in this new report on S-TRAC focused on adverse events and patient-reported outcomes.

The most common adverse events in the sunitinib arm of S-TRAC included diarrhea in 56.9%, versus 21.4% in the placebo arm, palmar-plantar erythrodysesthesia (PPE) in 50.3% versus 10.2% for placebo, and hypertension in 36.9% versus 11.8% for placebo. The frequency of serious adverse events was similar between arms, according to the investigators, at 21.9% for sunitinib and 17.1% for placebo.

Adverse events were the most common reason for dose reduction, cited in 34.6% of cases, and for dose interruption, reported in 46.4%, they said.

Treatment discontinuations due to adverse events occurred in 28.1%, usually because of PPE.

The S-TRAC study investigators used the EORTC QLQ-C30 instrument to evaluate patient experience during treatment.

That evaluation included an analysis of global health status/quality of life score that favored placebo, with a mean difference in the overall means of –4.76. Although statistically significant (P greater than or equal to .0001), the point estimate of the difference was below the commonly accepted threshold that would indicate clinically meaningful deterioration, investigators said.

Similar patterns that were statistically significant but not clinically meaningful were seen for symptoms including fatigue and pain. However, patient-reported scores for diarrhea and loss of appetite did reach the level of a clinically meaningful difference.

But only one patient permanently discontinued sunitinib because of diarrhea, and none permanently discontinued because of loss of appetite, Dr. Staehler and his coauthors noted.

The work was sponsored by Pfizer. Dr. Staehler reported honoraria, consulting fees, and research grants from Pfizer, Bayer, GSK, Roche, BMS, Novartis, Exelixis, and AVEO. Coauthors reported disclosures related to Merck, Sanofi, Astellas, Celldex, Acerta, Janssen, and others.

SOURCE: Staehler M et al. Ann Oncol. 2018 Aug 23. doi: 10.1093/annonc/mdy329.

Young adults with autism – particularly those with no intellectual disability – are at a higher risk of depression than their counterparts without autism, according to results of a Swedish population-based study.

Furthermore, the study found that young adults with autism spectrum disorders (ASD) also are at an increased risk of depression than their nonautistic siblings, reported Dheeraj Rai, MRCPsych, PhD, and his coauthors on JAMA Network Open Psychiatry.

“Because of the likelihood of a substantial overrepresentation of depression among individuals with ASD, a greater focus on timely identification and management of depression is important considering that it is a potentially treatable cause of distress, disability, and suicidal behaviors,” wrote Dr. Rai of the Centre for Academic Mental Health at the University of Bristol (United Kingdom) and his coauthors.

Previously, the burden of depression was thought to be high among individuals with ASD, but this is only the second longitudinal study to demonstrate an increased depression risk in adults with ASD, compared with the general population, the investigators wrote.

The study, called the Stockholm Youth Cohort, included data on children and young people who lived in Stockholm County, Sweden, between 2001 and 2011. The cohort included a total of 223,842 individuals who were followed until they were aged at least 18 years, of whom 4,073 had a diagnosis of ASD (mean age, 21.5 years; 65.9% male).

A total of 19.8% of individuals with ASD received a depression diagnosis between the ages of 18 and 27, compared with 6% of individuals with no ASD diagnosis, investigators found.

Depression diagnosis was more likely in those who had ASD with no intellectual disability, with an adjusted risk ratio of 4.28 (95% confidence interval, 4.00-4.58), compared with 1.81 (95% CI, 1.51-2.17) for ASD with intellectual disability, they reported.

The investigators also identified siblings of individuals with ASD using data from a Swedish registry. Individuals with ASD had more than a twofold greater depression diagnosis risk, compared with nonautistic full siblings (adjusted odds ratio, 2.50; 95% CI, 1.91-3.27).

“This association also seemed largely driven by an overrepresentation of depression in ASD without intellectual disability,” Dr. Rai and his coauthors wrote.

Those nonautistic siblings also had a somewhat higher risk of a depression diagnosis versus population controls, with adjusted risk ratios of 1.37 for full siblings and 1.42 for half siblings, they added.

Sibling comparisons in this study suggested “environmental pathways” in the association between autism and depression, according to authors.

“Studies identifying such pathways could assist in the development of preventive strategies or interventions,” they wrote.

Limitations of the study include the possibility of misclassification of depression diagnoses. Nevertheless, they said, the findings have implications for clinical practice and future research.

Dr. Rai reported receiving grants from The Baily Thomas Charitable Foundation, the National Institute for Health Research, and the Swedish Research Council for Health, Working Life and Welfare during the conduct of the study. His coauthors reported no other disclosures.

SOURCE: Rai D et al. JAMA Network Open. 2018 Aug 31. doi: 10.1001/jamanetworkopen.2018.1465.

Young adults with autism – particularly those with no intellectual disability – are at a higher risk of depression than their counterparts without autism, according to results of a Swedish population-based study.

Furthermore, the study found that young adults with autism spectrum disorders (ASD) also are at an increased risk of depression than their nonautistic siblings, reported Dheeraj Rai, MRCPsych, PhD, and his coauthors on JAMA Network Open Psychiatry.

“Because of the likelihood of a substantial overrepresentation of depression among individuals with ASD, a greater focus on timely identification and management of depression is important considering that it is a potentially treatable cause of distress, disability, and suicidal behaviors,” wrote Dr. Rai of the Centre for Academic Mental Health at the University of Bristol (United Kingdom) and his coauthors.

Previously, the burden of depression was thought to be high among individuals with ASD, but this is only the second longitudinal study to demonstrate an increased depression risk in adults with ASD, compared with the general population, the investigators wrote.

The study, called the Stockholm Youth Cohort, included data on children and young people who lived in Stockholm County, Sweden, between 2001 and 2011. The cohort included a total of 223,842 individuals who were followed until they were aged at least 18 years, of whom 4,073 had a diagnosis of ASD (mean age, 21.5 years; 65.9% male).

A total of 19.8% of individuals with ASD received a depression diagnosis between the ages of 18 and 27, compared with 6% of individuals with no ASD diagnosis, investigators found.

Depression diagnosis was more likely in those who had ASD with no intellectual disability, with an adjusted risk ratio of 4.28 (95% confidence interval, 4.00-4.58), compared with 1.81 (95% CI, 1.51-2.17) for ASD with intellectual disability, they reported.

The investigators also identified siblings of individuals with ASD using data from a Swedish registry. Individuals with ASD had more than a twofold greater depression diagnosis risk, compared with nonautistic full siblings (adjusted odds ratio, 2.50; 95% CI, 1.91-3.27).

“This association also seemed largely driven by an overrepresentation of depression in ASD without intellectual disability,” Dr. Rai and his coauthors wrote.

Those nonautistic siblings also had a somewhat higher risk of a depression diagnosis versus population controls, with adjusted risk ratios of 1.37 for full siblings and 1.42 for half siblings, they added.

Sibling comparisons in this study suggested “environmental pathways” in the association between autism and depression, according to authors.

“Studies identifying such pathways could assist in the development of preventive strategies or interventions,” they wrote.

Limitations of the study include the possibility of misclassification of depression diagnoses. Nevertheless, they said, the findings have implications for clinical practice and future research.

Dr. Rai reported receiving grants from The Baily Thomas Charitable Foundation, the National Institute for Health Research, and the Swedish Research Council for Health, Working Life and Welfare during the conduct of the study. His coauthors reported no other disclosures.

SOURCE: Rai D et al. JAMA Network Open. 2018 Aug 31. doi: 10.1001/jamanetworkopen.2018.1465.

Young adults with autism – particularly those with no intellectual disability – are at a higher risk of depression than their counterparts without autism, according to results of a Swedish population-based study.

Furthermore, the study found that young adults with autism spectrum disorders (ASD) also are at an increased risk of depression than their nonautistic siblings, reported Dheeraj Rai, MRCPsych, PhD, and his coauthors on JAMA Network Open Psychiatry.

“Because of the likelihood of a substantial overrepresentation of depression among individuals with ASD, a greater focus on timely identification and management of depression is important considering that it is a potentially treatable cause of distress, disability, and suicidal behaviors,” wrote Dr. Rai of the Centre for Academic Mental Health at the University of Bristol (United Kingdom) and his coauthors.

Previously, the burden of depression was thought to be high among individuals with ASD, but this is only the second longitudinal study to demonstrate an increased depression risk in adults with ASD, compared with the general population, the investigators wrote.

The study, called the Stockholm Youth Cohort, included data on children and young people who lived in Stockholm County, Sweden, between 2001 and 2011. The cohort included a total of 223,842 individuals who were followed until they were aged at least 18 years, of whom 4,073 had a diagnosis of ASD (mean age, 21.5 years; 65.9% male).

A total of 19.8% of individuals with ASD received a depression diagnosis between the ages of 18 and 27, compared with 6% of individuals with no ASD diagnosis, investigators found.

Depression diagnosis was more likely in those who had ASD with no intellectual disability, with an adjusted risk ratio of 4.28 (95% confidence interval, 4.00-4.58), compared with 1.81 (95% CI, 1.51-2.17) for ASD with intellectual disability, they reported.

The investigators also identified siblings of individuals with ASD using data from a Swedish registry. Individuals with ASD had more than a twofold greater depression diagnosis risk, compared with nonautistic full siblings (adjusted odds ratio, 2.50; 95% CI, 1.91-3.27).

“This association also seemed largely driven by an overrepresentation of depression in ASD without intellectual disability,” Dr. Rai and his coauthors wrote.

Those nonautistic siblings also had a somewhat higher risk of a depression diagnosis versus population controls, with adjusted risk ratios of 1.37 for full siblings and 1.42 for half siblings, they added.

Sibling comparisons in this study suggested “environmental pathways” in the association between autism and depression, according to authors.

“Studies identifying such pathways could assist in the development of preventive strategies or interventions,” they wrote.

Limitations of the study include the possibility of misclassification of depression diagnoses. Nevertheless, they said, the findings have implications for clinical practice and future research.

Dr. Rai reported receiving grants from The Baily Thomas Charitable Foundation, the National Institute for Health Research, and the Swedish Research Council for Health, Working Life and Welfare during the conduct of the study. His coauthors reported no other disclosures.

SOURCE: Rai D et al. JAMA Network Open. 2018 Aug 31. doi: 10.1001/jamanetworkopen.2018.1465.

© Nevit Dilmen

Preexisting osteoporosis is an important risk factor for mortality in postmenopausal women who develop multiple myeloma (MM), according to researchers.

They found that high fracture risk was associated with an increased risk of death in postmenopausal females with MM, independent of other clinical risk factors.

Ashley E. Rosko, MD, of Ohio State University in Columbus, and her colleagues reported these findings in Clinical Lymphoma, Myeloma and Leukemia.

The researchers studied 362 subjects in the Women’s Health Initiative data set who developed MM but had no history of any cancer at baseline. The women were between 50 and 79 years of age and postmenopausal when they were originally recruited at 40 US centers between 1993 and 1998.

Dr. Rosko and her colleagues calculated bone health for the women using the Fracture Risk Assessment Tool (FRAX), a web-based tool that calculates 10-year probability of hip and other major osteoporotic fractures.

Ninety-eight of the subjects were classified as having high FRAX scores, defined as a 10-year probability of 3% or greater for hip fracture or 20% or greater for other major osteoporosis-related fractures.

With a median follow-up of 10.5 years, the adjusted risk of death was elevated in women with high FRAX scores, with a covariate-adjusted hazard ratio of 1.51 (95% confidence interval, 1.01-2.25; P=0.044) versus women with low FRAX scores.

Of the 362 patients, 226 died during the follow-up period. That included 72% (n=71) of women with high FRAX scores and 59% (n=155) of women with low FRAX scores.

These findings suggest osteoporosis is an “important comorbidity” in women who develop MM, according to Dr. Rosko and her coauthors.

“Recognizing osteoporosis as a risk factor associated with multiple myeloma mortality is an important prognostic factor in postmenopausal women,” the researchers wrote.

This work was supported, in part, by the National Cancer Institute. The researchers reported no relevant financial disclosures.

© Nevit Dilmen

Preexisting osteoporosis is an important risk factor for mortality in postmenopausal women who develop multiple myeloma (MM), according to researchers.

They found that high fracture risk was associated with an increased risk of death in postmenopausal females with MM, independent of other clinical risk factors.

Ashley E. Rosko, MD, of Ohio State University in Columbus, and her colleagues reported these findings in Clinical Lymphoma, Myeloma and Leukemia.

The researchers studied 362 subjects in the Women’s Health Initiative data set who developed MM but had no history of any cancer at baseline. The women were between 50 and 79 years of age and postmenopausal when they were originally recruited at 40 US centers between 1993 and 1998.

Dr. Rosko and her colleagues calculated bone health for the women using the Fracture Risk Assessment Tool (FRAX), a web-based tool that calculates 10-year probability of hip and other major osteoporotic fractures.

Ninety-eight of the subjects were classified as having high FRAX scores, defined as a 10-year probability of 3% or greater for hip fracture or 20% or greater for other major osteoporosis-related fractures.

With a median follow-up of 10.5 years, the adjusted risk of death was elevated in women with high FRAX scores, with a covariate-adjusted hazard ratio of 1.51 (95% confidence interval, 1.01-2.25; P=0.044) versus women with low FRAX scores.

Of the 362 patients, 226 died during the follow-up period. That included 72% (n=71) of women with high FRAX scores and 59% (n=155) of women with low FRAX scores.

These findings suggest osteoporosis is an “important comorbidity” in women who develop MM, according to Dr. Rosko and her coauthors.

“Recognizing osteoporosis as a risk factor associated with multiple myeloma mortality is an important prognostic factor in postmenopausal women,” the researchers wrote.

This work was supported, in part, by the National Cancer Institute. The researchers reported no relevant financial disclosures.

© Nevit Dilmen

Preexisting osteoporosis is an important risk factor for mortality in postmenopausal women who develop multiple myeloma (MM), according to researchers.

They found that high fracture risk was associated with an increased risk of death in postmenopausal females with MM, independent of other clinical risk factors.

Ashley E. Rosko, MD, of Ohio State University in Columbus, and her colleagues reported these findings in Clinical Lymphoma, Myeloma and Leukemia.

The researchers studied 362 subjects in the Women’s Health Initiative data set who developed MM but had no history of any cancer at baseline. The women were between 50 and 79 years of age and postmenopausal when they were originally recruited at 40 US centers between 1993 and 1998.

Dr. Rosko and her colleagues calculated bone health for the women using the Fracture Risk Assessment Tool (FRAX), a web-based tool that calculates 10-year probability of hip and other major osteoporotic fractures.

Ninety-eight of the subjects were classified as having high FRAX scores, defined as a 10-year probability of 3% or greater for hip fracture or 20% or greater for other major osteoporosis-related fractures.

With a median follow-up of 10.5 years, the adjusted risk of death was elevated in women with high FRAX scores, with a covariate-adjusted hazard ratio of 1.51 (95% confidence interval, 1.01-2.25; P=0.044) versus women with low FRAX scores.

Of the 362 patients, 226 died during the follow-up period. That included 72% (n=71) of women with high FRAX scores and 59% (n=155) of women with low FRAX scores.

These findings suggest osteoporosis is an “important comorbidity” in women who develop MM, according to Dr. Rosko and her coauthors.

“Recognizing osteoporosis as a risk factor associated with multiple myeloma mortality is an important prognostic factor in postmenopausal women,” the researchers wrote.

This work was supported, in part, by the National Cancer Institute. The researchers reported no relevant financial disclosures.