Neither the first nor second dose of the monovalent rotavirus vaccine increased the risk of intussusception in the 3 weeks after immunization, a recent study found.

“This finding contrasts with previous studies in high- and upper-middle-income countries, in which an association with intussusception was found,” Jacqueline E. Tate, PhD, of the Centers for Disease Control and Prevention, and her associates reported in the New England Journal of Medicine.

Esben H/iStock/Getty Images

SOURCE: Tate JE et al. N Engl J Med. 2018;378:1521-8.

Neither the first nor second dose of the monovalent rotavirus vaccine increased the risk of intussusception in the 3 weeks after immunization, a recent study found.

“This finding contrasts with previous studies in high- and upper-middle-income countries, in which an association with intussusception was found,” Jacqueline E. Tate, PhD, of the Centers for Disease Control and Prevention, and her associates reported in the New England Journal of Medicine.

Esben H/iStock/Getty Images

SOURCE: Tate JE et al. N Engl J Med. 2018;378:1521-8.

Neither the first nor second dose of the monovalent rotavirus vaccine increased the risk of intussusception in the 3 weeks after immunization, a recent study found.

“This finding contrasts with previous studies in high- and upper-middle-income countries, in which an association with intussusception was found,” Jacqueline E. Tate, PhD, of the Centers for Disease Control and Prevention, and her associates reported in the New England Journal of Medicine.

Esben H/iStock/Getty Images

SOURCE: Tate JE et al. N Engl J Med. 2018;378:1521-8.

Ambulatory measurements of blood pressure more strongly predicted all-cause and cardiovascular mortality than did BP measured in the clinic, according to analysis of a large patient registry in Spain.

The results also showed an increased risk of death associated with white coat hypertension and an even stronger association between death and masked hypertension. They were published in the New England Journal of Medicine.

verbaska_studio/thinkstockphotos

Previous investigations had found that 24-hour ambulatory BP measurements were better predictors of patient outcomes than those obtained in the clinic or at home, but those investigations were small or population based.“In these studies, the number of clinical outcomes was limited, which reduced the ability to assess the predictive value of clinic blood pressure data as compared with ambulatory data,” reported José R. Banegas, MD, of the department of preventive medicine and public health at the Autonomous University of Madrid and his colleagues.

To better define the prognostic value of 24-hour ambulatory blood pressure measurement, Dr. Banegas and his colleagues looked at data on a large cohort of primary care patients in the Spanish Ambulatory Blood Pressure Registry. Their analysis included 63,910 adults recruited to the registry during 2004-2014.

Patients had blood pressure measurements taken in the clinic according to standard procedures. Afterward, they had ambulatory blood pressure monitoring that used an automated device programmed to record BP every 20 minutes during the day and every 30 minutes at night.

They found that overall clinic and ambulatory blood pressure measurements had a relatively similar magnitude of association with all-cause and cardiovascular mortality.

However, clinic systolic pressure lost its predictive power for all-cause mortality after adjustment for 24-hour ambulatory systolic pressure. The hazard ratio for all-cause mortality dropped from 1.54 before the adjustment to 1.02 after the adjustment, Dr. Banegas and his colleagues reported.

SOURCE: Banegas JR et al. N Engl J Med. 2018;378:1509-20.
 

Ambulatory measurements of blood pressure more strongly predicted all-cause and cardiovascular mortality than did BP measured in the clinic, according to analysis of a large patient registry in Spain.

The results also showed an increased risk of death associated with white coat hypertension and an even stronger association between death and masked hypertension. They were published in the New England Journal of Medicine.

verbaska_studio/thinkstockphotos

Previous investigations had found that 24-hour ambulatory BP measurements were better predictors of patient outcomes than those obtained in the clinic or at home, but those investigations were small or population based.“In these studies, the number of clinical outcomes was limited, which reduced the ability to assess the predictive value of clinic blood pressure data as compared with ambulatory data,” reported José R. Banegas, MD, of the department of preventive medicine and public health at the Autonomous University of Madrid and his colleagues.

To better define the prognostic value of 24-hour ambulatory blood pressure measurement, Dr. Banegas and his colleagues looked at data on a large cohort of primary care patients in the Spanish Ambulatory Blood Pressure Registry. Their analysis included 63,910 adults recruited to the registry during 2004-2014.

Patients had blood pressure measurements taken in the clinic according to standard procedures. Afterward, they had ambulatory blood pressure monitoring that used an automated device programmed to record BP every 20 minutes during the day and every 30 minutes at night.

They found that overall clinic and ambulatory blood pressure measurements had a relatively similar magnitude of association with all-cause and cardiovascular mortality.

However, clinic systolic pressure lost its predictive power for all-cause mortality after adjustment for 24-hour ambulatory systolic pressure. The hazard ratio for all-cause mortality dropped from 1.54 before the adjustment to 1.02 after the adjustment, Dr. Banegas and his colleagues reported.

SOURCE: Banegas JR et al. N Engl J Med. 2018;378:1509-20.
 

Ambulatory measurements of blood pressure more strongly predicted all-cause and cardiovascular mortality than did BP measured in the clinic, according to analysis of a large patient registry in Spain.

The results also showed an increased risk of death associated with white coat hypertension and an even stronger association between death and masked hypertension. They were published in the New England Journal of Medicine.

verbaska_studio/thinkstockphotos

Previous investigations had found that 24-hour ambulatory BP measurements were better predictors of patient outcomes than those obtained in the clinic or at home, but those investigations were small or population based.“In these studies, the number of clinical outcomes was limited, which reduced the ability to assess the predictive value of clinic blood pressure data as compared with ambulatory data,” reported José R. Banegas, MD, of the department of preventive medicine and public health at the Autonomous University of Madrid and his colleagues.

To better define the prognostic value of 24-hour ambulatory blood pressure measurement, Dr. Banegas and his colleagues looked at data on a large cohort of primary care patients in the Spanish Ambulatory Blood Pressure Registry. Their analysis included 63,910 adults recruited to the registry during 2004-2014.

Patients had blood pressure measurements taken in the clinic according to standard procedures. Afterward, they had ambulatory blood pressure monitoring that used an automated device programmed to record BP every 20 minutes during the day and every 30 minutes at night.

They found that overall clinic and ambulatory blood pressure measurements had a relatively similar magnitude of association with all-cause and cardiovascular mortality.

However, clinic systolic pressure lost its predictive power for all-cause mortality after adjustment for 24-hour ambulatory systolic pressure. The hazard ratio for all-cause mortality dropped from 1.54 before the adjustment to 1.02 after the adjustment, Dr. Banegas and his colleagues reported.

SOURCE: Banegas JR et al. N Engl J Med. 2018;378:1509-20.
 

A “time-out” is needed to reevaluate how quality measures are used as part of Medicare’s Merit-based Incentive Payment System (MIPS), according to officials at the American College of Physicians.

The call comes in the wake of an analysis of MIPS quality measures that found a majority are not valid for ambulatory care internal medicine, according to ACP criteria.

“We also determined that the proportion of the measures that had been developed by the National Committee for Quality Assurance [NCQA] or endorsed by the National Quality Forum [NQF] that were rated as valid by our method,” Dr. MacLean and colleagues wrote. “As compared with measures that were not endorsed by these organizations, greater percentages of NCQA-developed and NQF-endorsed measures were deemed valid [59% and 48%, respectively, vs. 27% for nonendorsed measures], and smaller percentages were deemed not valid [7% and 22% vs. 49% for nonendorsed measures].”

The lack of measures that were found to be valid for primary care is frustrating for doctors and could cause harm to patients, according to the authors.

“We need a time-out during which to assess and revise our approach to physician performance measurement,” they wrote.

The ACP recommends that “physicians with expertise in clinical medicine and research develop measures using clinically relevant methodology,” President Jack Ende said in a statement. “Performance measures should be fully integrated into care delivery so they can help address the most pressing performance gaps and direct quality improvement.”

The time-out call comes amidst differing opinions on how to proceed with the MIPS track of the Quality Payment Program. The Medicare Payment Advisory Commission has recommended to Congress that MIPS be repealed and replaced, while health care experts and physician associations believe the program should stay the course, given the investments that have been made already to accommodate the program’s reporting requirements.

[email protected]

SOURCE: MacLean CH et al. New Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMp1802595.

A “time-out” is needed to reevaluate how quality measures are used as part of Medicare’s Merit-based Incentive Payment System (MIPS), according to officials at the American College of Physicians.

The call comes in the wake of an analysis of MIPS quality measures that found a majority are not valid for ambulatory care internal medicine, according to ACP criteria.

“We also determined that the proportion of the measures that had been developed by the National Committee for Quality Assurance [NCQA] or endorsed by the National Quality Forum [NQF] that were rated as valid by our method,” Dr. MacLean and colleagues wrote. “As compared with measures that were not endorsed by these organizations, greater percentages of NCQA-developed and NQF-endorsed measures were deemed valid [59% and 48%, respectively, vs. 27% for nonendorsed measures], and smaller percentages were deemed not valid [7% and 22% vs. 49% for nonendorsed measures].”

The lack of measures that were found to be valid for primary care is frustrating for doctors and could cause harm to patients, according to the authors.

“We need a time-out during which to assess and revise our approach to physician performance measurement,” they wrote.

The ACP recommends that “physicians with expertise in clinical medicine and research develop measures using clinically relevant methodology,” President Jack Ende said in a statement. “Performance measures should be fully integrated into care delivery so they can help address the most pressing performance gaps and direct quality improvement.”

The time-out call comes amidst differing opinions on how to proceed with the MIPS track of the Quality Payment Program. The Medicare Payment Advisory Commission has recommended to Congress that MIPS be repealed and replaced, while health care experts and physician associations believe the program should stay the course, given the investments that have been made already to accommodate the program’s reporting requirements.

[email protected]

SOURCE: MacLean CH et al. New Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMp1802595.

A “time-out” is needed to reevaluate how quality measures are used as part of Medicare’s Merit-based Incentive Payment System (MIPS), according to officials at the American College of Physicians.

The call comes in the wake of an analysis of MIPS quality measures that found a majority are not valid for ambulatory care internal medicine, according to ACP criteria.

“We also determined that the proportion of the measures that had been developed by the National Committee for Quality Assurance [NCQA] or endorsed by the National Quality Forum [NQF] that were rated as valid by our method,” Dr. MacLean and colleagues wrote. “As compared with measures that were not endorsed by these organizations, greater percentages of NCQA-developed and NQF-endorsed measures were deemed valid [59% and 48%, respectively, vs. 27% for nonendorsed measures], and smaller percentages were deemed not valid [7% and 22% vs. 49% for nonendorsed measures].”

The lack of measures that were found to be valid for primary care is frustrating for doctors and could cause harm to patients, according to the authors.

“We need a time-out during which to assess and revise our approach to physician performance measurement,” they wrote.

The ACP recommends that “physicians with expertise in clinical medicine and research develop measures using clinically relevant methodology,” President Jack Ende said in a statement. “Performance measures should be fully integrated into care delivery so they can help address the most pressing performance gaps and direct quality improvement.”

The time-out call comes amidst differing opinions on how to proceed with the MIPS track of the Quality Payment Program. The Medicare Payment Advisory Commission has recommended to Congress that MIPS be repealed and replaced, while health care experts and physician associations believe the program should stay the course, given the investments that have been made already to accommodate the program’s reporting requirements.

[email protected]

SOURCE: MacLean CH et al. New Engl J Med. 2018 Apr 18. doi: 10.1056/NEJMp1802595.

Applying clinical Juvenile Arthritis Disease Activity Score criteria to identify clinically inactive disease in patients with juvenile idiopathic arthritis (JIA) resulted in patients with better long-term functional activity and psychosocial health outcomes, compared with patients whose disease state was assessed using Wallace’s preliminary criteria, according to recent research from the multicenter Childhood Arthritis Prospective Study.

“A challenge is in understanding how best to apply these results in the clinical setting,” wrote Stephanie J.W. Shoop-Worrall of the Arthritis Research UK Centre for Epidemiology at the University of Manchester (England) and her coauthors. “As achievement of CID [clinically inactive disease] according to cJADAS10 [clinical Juvenile Arthritis Disease Activity Score assessed in 10 joints] was associated with equivalent or superior outcomes to Wallace’s preliminary criteria and it is more feasible to complete in clinical practice, due to containing only three routinely collected components, one could argue that this is likely to be a superior treatment target for application in clinical practice.”

szefei/Thinkstock

“Wallace’s preliminary criteria includes five components, observed or measured by a physician, which must all be absent or in the normal range, but do not include an assessment by the patient or their proxy,” Ms. Shoop-Worrall and her colleagues wrote. “In contrast, the JADAS and cJADAS include fewer overall components, meaning they may be easier to complete in a routine clinical setting, but do include a patient or proxy subjective assessment of patient wellbeing.”

Of the patients analyzed, 68% had oligoarthritis, while 27% had RF-negative and 5% had RF-positive polyarticular JIA. Over half (56%) of patients did not achieve CID, while 21% had achieved CID through both definitions. A further 23% of patients achieved CID in only one definition – 16% of patients according to cJADAS10 and 7% of patients according to Wallace’s preliminary criteria. Patients who achieved CID had significantly increased odds of having no limited joints according to either cJADAS10 (odds ratio, 3.9; 95% confidence interval, 2.5-6.3) or Wallace’s preliminary criteria (OR, 7.5; 95% CI, 2.9-19.2). Patients had better Child Health Questionnaire psychosocial scores when they achieved CID according to either cJADAS10 (coefficient, 5.3; 95% CI, 0.5-10.1) or both cJADAS10 and Wallace’s preliminary criteria (coefficient, 5.5; 95% CI, 2.2-9.5).

When patients’ function was assessed using the Childhood Health Assessment questionnaire, they had significantly increased odds of having no disability recorded when they achieved CID with either cJADAS10 (OR, 4.5; 95% CI, 2.2-9.5) or both criteria (OR 5.2; 95% CI, 2.7-9.9). Patients assessed with Wallace’s preliminary criteria had “no better Child Health Questionnaire psychosocial scores or Childhood Health Assessment questionnaire scores than those with active disease at 1 year.” Most patients who achieved CID also achieved MDA, but 10% of patients reached MDA without achieving CID.

The researchers noted that reliance on either cJADAS10 or Wallace’s preliminary criteria alone may miss data needed for clinical treatment. Data obtained from cJADAS10 may lead to additional psychological and physiotherapy treatments not seen in Wallace’s preliminary criteria; however, “relying solely on Wallace’s preliminary criteria may guide immunosuppressive therapy very well, but may ignore other symptoms relevant to the patient.”

“As the two scores differ in their components one could argue that they are not capturing the same construct,” Ms. Shoop-Worrall and her associates wrote. “Wallace’s preliminary criteria capture more objective measures of inflammation, whilst the cJADAS10, through inclusion of a patient well-being measure, may also capture other noninflammatory components of the disease, such as chronic pain and fatigue, not captured by Wallace’s preliminary criteria.”

The authors reported having no relevant financial disclosures for this study.

SOURCE: Shoop‐Worrall SJW et al. Arthritis Rheumatol. 2018 April 12. doi: 10.1002/art.40519.

Applying clinical Juvenile Arthritis Disease Activity Score criteria to identify clinically inactive disease in patients with juvenile idiopathic arthritis (JIA) resulted in patients with better long-term functional activity and psychosocial health outcomes, compared with patients whose disease state was assessed using Wallace’s preliminary criteria, according to recent research from the multicenter Childhood Arthritis Prospective Study.

“A challenge is in understanding how best to apply these results in the clinical setting,” wrote Stephanie J.W. Shoop-Worrall of the Arthritis Research UK Centre for Epidemiology at the University of Manchester (England) and her coauthors. “As achievement of CID [clinically inactive disease] according to cJADAS10 [clinical Juvenile Arthritis Disease Activity Score assessed in 10 joints] was associated with equivalent or superior outcomes to Wallace’s preliminary criteria and it is more feasible to complete in clinical practice, due to containing only three routinely collected components, one could argue that this is likely to be a superior treatment target for application in clinical practice.”

szefei/Thinkstock

“Wallace’s preliminary criteria includes five components, observed or measured by a physician, which must all be absent or in the normal range, but do not include an assessment by the patient or their proxy,” Ms. Shoop-Worrall and her colleagues wrote. “In contrast, the JADAS and cJADAS include fewer overall components, meaning they may be easier to complete in a routine clinical setting, but do include a patient or proxy subjective assessment of patient wellbeing.”

Of the patients analyzed, 68% had oligoarthritis, while 27% had RF-negative and 5% had RF-positive polyarticular JIA. Over half (56%) of patients did not achieve CID, while 21% had achieved CID through both definitions. A further 23% of patients achieved CID in only one definition – 16% of patients according to cJADAS10 and 7% of patients according to Wallace’s preliminary criteria. Patients who achieved CID had significantly increased odds of having no limited joints according to either cJADAS10 (odds ratio, 3.9; 95% confidence interval, 2.5-6.3) or Wallace’s preliminary criteria (OR, 7.5; 95% CI, 2.9-19.2). Patients had better Child Health Questionnaire psychosocial scores when they achieved CID according to either cJADAS10 (coefficient, 5.3; 95% CI, 0.5-10.1) or both cJADAS10 and Wallace’s preliminary criteria (coefficient, 5.5; 95% CI, 2.2-9.5).

When patients’ function was assessed using the Childhood Health Assessment questionnaire, they had significantly increased odds of having no disability recorded when they achieved CID with either cJADAS10 (OR, 4.5; 95% CI, 2.2-9.5) or both criteria (OR 5.2; 95% CI, 2.7-9.9). Patients assessed with Wallace’s preliminary criteria had “no better Child Health Questionnaire psychosocial scores or Childhood Health Assessment questionnaire scores than those with active disease at 1 year.” Most patients who achieved CID also achieved MDA, but 10% of patients reached MDA without achieving CID.

The researchers noted that reliance on either cJADAS10 or Wallace’s preliminary criteria alone may miss data needed for clinical treatment. Data obtained from cJADAS10 may lead to additional psychological and physiotherapy treatments not seen in Wallace’s preliminary criteria; however, “relying solely on Wallace’s preliminary criteria may guide immunosuppressive therapy very well, but may ignore other symptoms relevant to the patient.”

“As the two scores differ in their components one could argue that they are not capturing the same construct,” Ms. Shoop-Worrall and her associates wrote. “Wallace’s preliminary criteria capture more objective measures of inflammation, whilst the cJADAS10, through inclusion of a patient well-being measure, may also capture other noninflammatory components of the disease, such as chronic pain and fatigue, not captured by Wallace’s preliminary criteria.”

The authors reported having no relevant financial disclosures for this study.

SOURCE: Shoop‐Worrall SJW et al. Arthritis Rheumatol. 2018 April 12. doi: 10.1002/art.40519.

Applying clinical Juvenile Arthritis Disease Activity Score criteria to identify clinically inactive disease in patients with juvenile idiopathic arthritis (JIA) resulted in patients with better long-term functional activity and psychosocial health outcomes, compared with patients whose disease state was assessed using Wallace’s preliminary criteria, according to recent research from the multicenter Childhood Arthritis Prospective Study.

“A challenge is in understanding how best to apply these results in the clinical setting,” wrote Stephanie J.W. Shoop-Worrall of the Arthritis Research UK Centre for Epidemiology at the University of Manchester (England) and her coauthors. “As achievement of CID [clinically inactive disease] according to cJADAS10 [clinical Juvenile Arthritis Disease Activity Score assessed in 10 joints] was associated with equivalent or superior outcomes to Wallace’s preliminary criteria and it is more feasible to complete in clinical practice, due to containing only three routinely collected components, one could argue that this is likely to be a superior treatment target for application in clinical practice.”

szefei/Thinkstock

“Wallace’s preliminary criteria includes five components, observed or measured by a physician, which must all be absent or in the normal range, but do not include an assessment by the patient or their proxy,” Ms. Shoop-Worrall and her colleagues wrote. “In contrast, the JADAS and cJADAS include fewer overall components, meaning they may be easier to complete in a routine clinical setting, but do include a patient or proxy subjective assessment of patient wellbeing.”

Of the patients analyzed, 68% had oligoarthritis, while 27% had RF-negative and 5% had RF-positive polyarticular JIA. Over half (56%) of patients did not achieve CID, while 21% had achieved CID through both definitions. A further 23% of patients achieved CID in only one definition – 16% of patients according to cJADAS10 and 7% of patients according to Wallace’s preliminary criteria. Patients who achieved CID had significantly increased odds of having no limited joints according to either cJADAS10 (odds ratio, 3.9; 95% confidence interval, 2.5-6.3) or Wallace’s preliminary criteria (OR, 7.5; 95% CI, 2.9-19.2). Patients had better Child Health Questionnaire psychosocial scores when they achieved CID according to either cJADAS10 (coefficient, 5.3; 95% CI, 0.5-10.1) or both cJADAS10 and Wallace’s preliminary criteria (coefficient, 5.5; 95% CI, 2.2-9.5).

When patients’ function was assessed using the Childhood Health Assessment questionnaire, they had significantly increased odds of having no disability recorded when they achieved CID with either cJADAS10 (OR, 4.5; 95% CI, 2.2-9.5) or both criteria (OR 5.2; 95% CI, 2.7-9.9). Patients assessed with Wallace’s preliminary criteria had “no better Child Health Questionnaire psychosocial scores or Childhood Health Assessment questionnaire scores than those with active disease at 1 year.” Most patients who achieved CID also achieved MDA, but 10% of patients reached MDA without achieving CID.

The researchers noted that reliance on either cJADAS10 or Wallace’s preliminary criteria alone may miss data needed for clinical treatment. Data obtained from cJADAS10 may lead to additional psychological and physiotherapy treatments not seen in Wallace’s preliminary criteria; however, “relying solely on Wallace’s preliminary criteria may guide immunosuppressive therapy very well, but may ignore other symptoms relevant to the patient.”

“As the two scores differ in their components one could argue that they are not capturing the same construct,” Ms. Shoop-Worrall and her associates wrote. “Wallace’s preliminary criteria capture more objective measures of inflammation, whilst the cJADAS10, through inclusion of a patient well-being measure, may also capture other noninflammatory components of the disease, such as chronic pain and fatigue, not captured by Wallace’s preliminary criteria.”

The authors reported having no relevant financial disclosures for this study.

SOURCE: Shoop‐Worrall SJW et al. Arthritis Rheumatol. 2018 April 12. doi: 10.1002/art.40519.

NEWPORT BEACH, CALIF. – Adding pembrolizumab after high-dose cytarabine in patients with relapsed or refractory acute myeloid leukemia (AML) appears safe and feasible and shows promising efficacy, according to early results from a multicenter phase 2 study.

The overall response rate to this novel treatment approach in 19 evaluable patients (of 20 enrolled to date) was 42%, with 7 patients (37%) achieving a complete response or complete response with incomplete blood count recovery, and 1 (5%) achieving a partial response, reported Joshua Zeidner, MD, in a poster at the Acute Leukemia Forum of Hemedicus.

Sharon Worcester/MDedge News

Preliminary analyses in the first six patients, including three with complete response and three nonresponders, showed increased posttreatment diversity of the T-cell receptor repertoire versus baseline in peripheral blood CD8+ T cells in the complete response patients, compared with nonresponders. This suggests that T-cell diversity at baseline is a promising biomarker for programmed death-1 (PD-1) blockade response, Dr. Zeidner noted.

PD-1 suppresses immune activation, and the PD-1 pathway is exploited by AML cells to evade immune surveillance, Dr. Zeidner explained. PD-1 blockade has been shown to have antileukemic effects in vivo, there is expression of multiple coinhibitory receptors in AML patients at the time of diagnosis (that persists in refractory AML), and the ligand for PD-1 is up-regulated on AML blasts, particularly in relapsed/refractory disease, he added.

He and his colleagues hypothesized that targeting PD-1 with pembrolizumab after high-dose cytarabine (HiDAC) salvage chemotherapy would stimulate a T cell–mediated antileukemic immune response and lead to improved efficacy in patients with relapsed or refractory AML.

The ongoing study, with planned enrollment of 37 patients, includes patients aged 18-70 years with relapsed/refractory AML (median age of first 20 enrolled is 54 years). Those under age 60 years receive 2 g/m² of intravenous HiDAC every 12 hours on days 1-5, and those over age 60 years receive 1.5 g/m² every 12 hours on days 1-5. In both age groups, this is followed by intravenous pembrolizumab given at 200 mg on day 14.

Overall responders receive maintenance phase intravenous pembrolizumab at 200 mg every 3 weeks for up to 2 years until relapse or progression. Patients are allowed to proceed to stem cell transplant before or after the maintenance phase.

A number of correlative studies, including serial peripheral blood and bone marrow flow cytometry and T-cell receptor clonality studies, also are being conducted to look for predictive biomarkers of response, Dr. Zeidner said.

The study population to date is a relatively young, very-high-risk subgroup of AML patients; European LeukemiaNet-2017 genetic risk status was favorable in only 3 of the first 20 patients (15%), intermediate in 7 (35%), and adverse in 10 (50%). Treatment has been well tolerated; toxicities have been rare and manageable. “Overall, there have been no unexpected toxicities,” he said.

The most common overall toxicities included febrile neutropenia in 70% of patients; transaminitis (including one grade 3 case) in 50%, hyperbilirubinemia in 35%, and fatigue, increased alkaline phosphatase, and rash in 25% each.

Novel therapies for relapsed/refractory AML are urgently needed, and these early results demonstrated the safety and feasibility of adding pembrolizumab after HiDAC chemotherapy in relapsed/refractory AML patients. The preliminary finding that broadening of the immune repertoire, which may occur via increasing T-cell responses beyond endogenous viral responses, was associated with complete response was particularly encouraging, Dr. Zeidner said. The investigators hope to determine predictors of response to immune checkpoint blockade in AML through a comprehensive immune biomarker discovery approach, he added.

This study was funded by Merck. Dr. Zeidner reported having no financial disclosures. The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

SOURCE: Zeidner J et al. ALF 2018, Poster Session.

NEWPORT BEACH, CALIF. – Adding pembrolizumab after high-dose cytarabine in patients with relapsed or refractory acute myeloid leukemia (AML) appears safe and feasible and shows promising efficacy, according to early results from a multicenter phase 2 study.

The overall response rate to this novel treatment approach in 19 evaluable patients (of 20 enrolled to date) was 42%, with 7 patients (37%) achieving a complete response or complete response with incomplete blood count recovery, and 1 (5%) achieving a partial response, reported Joshua Zeidner, MD, in a poster at the Acute Leukemia Forum of Hemedicus.

Sharon Worcester/MDedge News

Preliminary analyses in the first six patients, including three with complete response and three nonresponders, showed increased posttreatment diversity of the T-cell receptor repertoire versus baseline in peripheral blood CD8+ T cells in the complete response patients, compared with nonresponders. This suggests that T-cell diversity at baseline is a promising biomarker for programmed death-1 (PD-1) blockade response, Dr. Zeidner noted.

PD-1 suppresses immune activation, and the PD-1 pathway is exploited by AML cells to evade immune surveillance, Dr. Zeidner explained. PD-1 blockade has been shown to have antileukemic effects in vivo, there is expression of multiple coinhibitory receptors in AML patients at the time of diagnosis (that persists in refractory AML), and the ligand for PD-1 is up-regulated on AML blasts, particularly in relapsed/refractory disease, he added.

He and his colleagues hypothesized that targeting PD-1 with pembrolizumab after high-dose cytarabine (HiDAC) salvage chemotherapy would stimulate a T cell–mediated antileukemic immune response and lead to improved efficacy in patients with relapsed or refractory AML.

The ongoing study, with planned enrollment of 37 patients, includes patients aged 18-70 years with relapsed/refractory AML (median age of first 20 enrolled is 54 years). Those under age 60 years receive 2 g/m² of intravenous HiDAC every 12 hours on days 1-5, and those over age 60 years receive 1.5 g/m² every 12 hours on days 1-5. In both age groups, this is followed by intravenous pembrolizumab given at 200 mg on day 14.

Overall responders receive maintenance phase intravenous pembrolizumab at 200 mg every 3 weeks for up to 2 years until relapse or progression. Patients are allowed to proceed to stem cell transplant before or after the maintenance phase.

A number of correlative studies, including serial peripheral blood and bone marrow flow cytometry and T-cell receptor clonality studies, also are being conducted to look for predictive biomarkers of response, Dr. Zeidner said.

The study population to date is a relatively young, very-high-risk subgroup of AML patients; European LeukemiaNet-2017 genetic risk status was favorable in only 3 of the first 20 patients (15%), intermediate in 7 (35%), and adverse in 10 (50%). Treatment has been well tolerated; toxicities have been rare and manageable. “Overall, there have been no unexpected toxicities,” he said.

The most common overall toxicities included febrile neutropenia in 70% of patients; transaminitis (including one grade 3 case) in 50%, hyperbilirubinemia in 35%, and fatigue, increased alkaline phosphatase, and rash in 25% each.

Novel therapies for relapsed/refractory AML are urgently needed, and these early results demonstrated the safety and feasibility of adding pembrolizumab after HiDAC chemotherapy in relapsed/refractory AML patients. The preliminary finding that broadening of the immune repertoire, which may occur via increasing T-cell responses beyond endogenous viral responses, was associated with complete response was particularly encouraging, Dr. Zeidner said. The investigators hope to determine predictors of response to immune checkpoint blockade in AML through a comprehensive immune biomarker discovery approach, he added.

This study was funded by Merck. Dr. Zeidner reported having no financial disclosures. The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

SOURCE: Zeidner J et al. ALF 2018, Poster Session.

NEWPORT BEACH, CALIF. – Adding pembrolizumab after high-dose cytarabine in patients with relapsed or refractory acute myeloid leukemia (AML) appears safe and feasible and shows promising efficacy, according to early results from a multicenter phase 2 study.

The overall response rate to this novel treatment approach in 19 evaluable patients (of 20 enrolled to date) was 42%, with 7 patients (37%) achieving a complete response or complete response with incomplete blood count recovery, and 1 (5%) achieving a partial response, reported Joshua Zeidner, MD, in a poster at the Acute Leukemia Forum of Hemedicus.

Sharon Worcester/MDedge News

Preliminary analyses in the first six patients, including three with complete response and three nonresponders, showed increased posttreatment diversity of the T-cell receptor repertoire versus baseline in peripheral blood CD8+ T cells in the complete response patients, compared with nonresponders. This suggests that T-cell diversity at baseline is a promising biomarker for programmed death-1 (PD-1) blockade response, Dr. Zeidner noted.

PD-1 suppresses immune activation, and the PD-1 pathway is exploited by AML cells to evade immune surveillance, Dr. Zeidner explained. PD-1 blockade has been shown to have antileukemic effects in vivo, there is expression of multiple coinhibitory receptors in AML patients at the time of diagnosis (that persists in refractory AML), and the ligand for PD-1 is up-regulated on AML blasts, particularly in relapsed/refractory disease, he added.

He and his colleagues hypothesized that targeting PD-1 with pembrolizumab after high-dose cytarabine (HiDAC) salvage chemotherapy would stimulate a T cell–mediated antileukemic immune response and lead to improved efficacy in patients with relapsed or refractory AML.

The ongoing study, with planned enrollment of 37 patients, includes patients aged 18-70 years with relapsed/refractory AML (median age of first 20 enrolled is 54 years). Those under age 60 years receive 2 g/m² of intravenous HiDAC every 12 hours on days 1-5, and those over age 60 years receive 1.5 g/m² every 12 hours on days 1-5. In both age groups, this is followed by intravenous pembrolizumab given at 200 mg on day 14.

Overall responders receive maintenance phase intravenous pembrolizumab at 200 mg every 3 weeks for up to 2 years until relapse or progression. Patients are allowed to proceed to stem cell transplant before or after the maintenance phase.

A number of correlative studies, including serial peripheral blood and bone marrow flow cytometry and T-cell receptor clonality studies, also are being conducted to look for predictive biomarkers of response, Dr. Zeidner said.

The study population to date is a relatively young, very-high-risk subgroup of AML patients; European LeukemiaNet-2017 genetic risk status was favorable in only 3 of the first 20 patients (15%), intermediate in 7 (35%), and adverse in 10 (50%). Treatment has been well tolerated; toxicities have been rare and manageable. “Overall, there have been no unexpected toxicities,” he said.

The most common overall toxicities included febrile neutropenia in 70% of patients; transaminitis (including one grade 3 case) in 50%, hyperbilirubinemia in 35%, and fatigue, increased alkaline phosphatase, and rash in 25% each.

Novel therapies for relapsed/refractory AML are urgently needed, and these early results demonstrated the safety and feasibility of adding pembrolizumab after HiDAC chemotherapy in relapsed/refractory AML patients. The preliminary finding that broadening of the immune repertoire, which may occur via increasing T-cell responses beyond endogenous viral responses, was associated with complete response was particularly encouraging, Dr. Zeidner said. The investigators hope to determine predictors of response to immune checkpoint blockade in AML through a comprehensive immune biomarker discovery approach, he added.

This study was funded by Merck. Dr. Zeidner reported having no financial disclosures. The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

SOURCE: Zeidner J et al. ALF 2018, Poster Session.

A new study highlights a marked delay between completion of clinical trials and when the results reach practicing clinicians.

The study, published online in JAMA Oncology, found that even for the most pressing findings, the median publication of final clinical data is nearly 1 year.

Lindor Qunaj of Brown University, Providence, R.I., and colleagues measured the time frame between when eight large pharmaceutical companies issued press releases announcing completed phase 3 oncology clinical trials and the public sharing of the results either on ClinicalTrials.gov or a peer-reviewed biomedical journal. Collectively, the eight companies accounted for 72% of all oncology sales in 2015. The press releases were posted between January 2011 and June 2016. Investigators found the median time from press release to publication of data was 300 days.

Clinical trials with negative results had median delays of more than 100 days longer than positive results, the investigators found. Of the 100 press releases studied, only 31% included the magnitude of study findings. Most press releases (66%) reported outcomes of studies involving drugs already approved by the Food and Drug Administration for some indication. Press releases regarding preapproval drugs were less likely to contain quantitative reports of effect sizes. The majority of final clinical results (90%) were either posted, published, or both, within 2 years. No difference existed in the median delay between trials studying approved drugs compared with unapproved drugs.

Mr. Qunaj and associates noted that their analysis emphasizes the ongoing criticism of the speed at which pharmaceutical companies publish findings from clinical trials. The authors suggested that pharmaceutical companies, publishers, and journals work to minimize such delays. For instance, they might consider preprinting, the practice of publishing “draft” findings prior to, or in tandem with, peer review. Through preprints, companies could post all relevant study data, including measured outcomes and toxic effects, as well as study protocol, Mr. Qunaj and associates wrote. In addition, the authors suggested that publishers continue to consider innovative efforts to “responsibly accelerate the peer review process, or to further shorten the time between manuscript acceptance and data availability.”

“We do foresee possible objections from pharmaceutical companies, scientific journals, and medical societies,” the authors wrote. “Embargoed, timed data releases are a potent tool for marketing study findings and drawing traffic to the journal or meeting where the results are presented. However, these interests are narrow, while the needs of science more generally, and the patients with the conditions that these companies have studied, matter more.”

A coauthor, Peter Bach, MD, received personal fees and grants from numerous sources. No other disclosures were reported.

SOURCE: Qunaj L et al. JAMA Oncol. 2018 Apr 12. doi:10.1001/jamaoncol.2018.0264.

A new study highlights a marked delay between completion of clinical trials and when the results reach practicing clinicians.

The study, published online in JAMA Oncology, found that even for the most pressing findings, the median publication of final clinical data is nearly 1 year.

Lindor Qunaj of Brown University, Providence, R.I., and colleagues measured the time frame between when eight large pharmaceutical companies issued press releases announcing completed phase 3 oncology clinical trials and the public sharing of the results either on ClinicalTrials.gov or a peer-reviewed biomedical journal. Collectively, the eight companies accounted for 72% of all oncology sales in 2015. The press releases were posted between January 2011 and June 2016. Investigators found the median time from press release to publication of data was 300 days.

Clinical trials with negative results had median delays of more than 100 days longer than positive results, the investigators found. Of the 100 press releases studied, only 31% included the magnitude of study findings. Most press releases (66%) reported outcomes of studies involving drugs already approved by the Food and Drug Administration for some indication. Press releases regarding preapproval drugs were less likely to contain quantitative reports of effect sizes. The majority of final clinical results (90%) were either posted, published, or both, within 2 years. No difference existed in the median delay between trials studying approved drugs compared with unapproved drugs.

Mr. Qunaj and associates noted that their analysis emphasizes the ongoing criticism of the speed at which pharmaceutical companies publish findings from clinical trials. The authors suggested that pharmaceutical companies, publishers, and journals work to minimize such delays. For instance, they might consider preprinting, the practice of publishing “draft” findings prior to, or in tandem with, peer review. Through preprints, companies could post all relevant study data, including measured outcomes and toxic effects, as well as study protocol, Mr. Qunaj and associates wrote. In addition, the authors suggested that publishers continue to consider innovative efforts to “responsibly accelerate the peer review process, or to further shorten the time between manuscript acceptance and data availability.”

“We do foresee possible objections from pharmaceutical companies, scientific journals, and medical societies,” the authors wrote. “Embargoed, timed data releases are a potent tool for marketing study findings and drawing traffic to the journal or meeting where the results are presented. However, these interests are narrow, while the needs of science more generally, and the patients with the conditions that these companies have studied, matter more.”

A coauthor, Peter Bach, MD, received personal fees and grants from numerous sources. No other disclosures were reported.

SOURCE: Qunaj L et al. JAMA Oncol. 2018 Apr 12. doi:10.1001/jamaoncol.2018.0264.

A new study highlights a marked delay between completion of clinical trials and when the results reach practicing clinicians.

The study, published online in JAMA Oncology, found that even for the most pressing findings, the median publication of final clinical data is nearly 1 year.

Lindor Qunaj of Brown University, Providence, R.I., and colleagues measured the time frame between when eight large pharmaceutical companies issued press releases announcing completed phase 3 oncology clinical trials and the public sharing of the results either on ClinicalTrials.gov or a peer-reviewed biomedical journal. Collectively, the eight companies accounted for 72% of all oncology sales in 2015. The press releases were posted between January 2011 and June 2016. Investigators found the median time from press release to publication of data was 300 days.

Clinical trials with negative results had median delays of more than 100 days longer than positive results, the investigators found. Of the 100 press releases studied, only 31% included the magnitude of study findings. Most press releases (66%) reported outcomes of studies involving drugs already approved by the Food and Drug Administration for some indication. Press releases regarding preapproval drugs were less likely to contain quantitative reports of effect sizes. The majority of final clinical results (90%) were either posted, published, or both, within 2 years. No difference existed in the median delay between trials studying approved drugs compared with unapproved drugs.

Mr. Qunaj and associates noted that their analysis emphasizes the ongoing criticism of the speed at which pharmaceutical companies publish findings from clinical trials. The authors suggested that pharmaceutical companies, publishers, and journals work to minimize such delays. For instance, they might consider preprinting, the practice of publishing “draft” findings prior to, or in tandem with, peer review. Through preprints, companies could post all relevant study data, including measured outcomes and toxic effects, as well as study protocol, Mr. Qunaj and associates wrote. In addition, the authors suggested that publishers continue to consider innovative efforts to “responsibly accelerate the peer review process, or to further shorten the time between manuscript acceptance and data availability.”

“We do foresee possible objections from pharmaceutical companies, scientific journals, and medical societies,” the authors wrote. “Embargoed, timed data releases are a potent tool for marketing study findings and drawing traffic to the journal or meeting where the results are presented. However, these interests are narrow, while the needs of science more generally, and the patients with the conditions that these companies have studied, matter more.”

A coauthor, Peter Bach, MD, received personal fees and grants from numerous sources. No other disclosures were reported.

SOURCE: Qunaj L et al. JAMA Oncol. 2018 Apr 12. doi:10.1001/jamaoncol.2018.0264.

For patients with relapsed or refractory chronic lymphocytic leukemia despite therapy with idelalisib (Zydelig), venetoclax (Venclexta) was associated with relatively high overall response and progression-free survival rates, results of a phase 2 study show.

Among 36 patients with relapsed/refractory CLL who had received idelalisib as their most recent B-cell receptor pathway inhibitor (BCRi), the overall response rate (ORR) was 67%, and median progression-free and overall survival (PFS and OS) had not been reached after 14 months of follow-up, reported Steven Coutre, MD, of Stanford (Calif.) University, and his colleagues.

“[V]enetoclax monotherapy is active and well-tolerated in patients with CLL progression after therapy with idelalisib, including a significant number of patients who also received prior therapy with ibrutinib [Imbruvica]. These results from the first prospective trial in this high-risk population provide evidence that venetoclax should be considered as a treatment option for such patients,” the investigators wrote. The report was published in Blood.

In clinical trials with idelalisib, approximately one-third of patients with CLL experienced disease progression on therapy, and other patients had to discontinue the drug, an inhibitor of the delta isoform of phosphoinositide 3-kinase (PI3K), because of toxicities, the investigators noted.

“The optimal treatment of patients with CLL progressing after idelalisib has not been well characterized,” they wrote. “Outcomes in patients who discontinued idelalisib treatment early are poor, with one retrospective analysis reporting a median overall survival (OS) after idelalisib discontinuation of approximately 2 months (range, 0-10 months).”

Venetoclax, an inhibitor of the apoptotic BCL-2 protein, has been shown to have activity against CLL, including in patients with high-risk features such as the chromosome 17p deletion (del17p), prompting the investigators to evaluate it as a follow-on in patients with relapsed/refractory CLL treated with a B-cell receptor pathway inhibitor.

They reported on the idelalisib cohort in a phase 2 trial in which patients with CLL that progressed on either idelalisib or ibrutinib were subsequently treated with venetoclax. The patients in this analysis included those treated with idelalisib in the main study cohort or an expansion cohort.

Patients were started on venetoclax 20 mg daily, followed by weekly dose escalations to a target of 400 mg daily by week 5, or to a maximum of 600 mg for patients who did not have a response by the week 12 assessment.

The overall response rate – the primary efficacy endpoint – was 67%. There were two complete remissions (CR) and one CR with incomplete bone marrow recovery. The remaining 21 patients with responses had partial responses.

At a median of 14 months of follow-up, neither median PFS, duration of response, or OS had been reached.

The investigator-estimated 12-month PFS rate was 79%.

The most common grade 3 or 4 adverse events were neutropenia in 50% of patients, thrombocytopenia in 25%, and anemia in 17%. There were no cases of clinical tumor lysis syndrome, which has been known to occur when venetoclax is initiated at full dose without a ramp-up.

The most common adverse events of any grade included neutropenia, diarrhea, upper respiratory tract infection, thrombocytopenia, nausea, fatigue, cough, rash, and anemia.

“The low number of CRs reported at the time of analysis may be a result of the follow-up time, particularly for patients in the expansion cohort, as other clinical studies with venetoclax report CR occurring after 1 year on therapy. Patients with prior ibrutinib exposure who had progressed on idelalisib as their most recent therapy before study entry had similar efficacy results,” the investigators wrote.

Genentech and AbbVie funded the study. Dr. Coutre is an advisory board member for both companies and others, and receives institutional funding from AbbVie and others. Multiple coauthors disclosed financial relationships with AbbVie, Genentech, or both, as well as other companies.

SOURCE: Coutre S et al. Blood. 2018;131(15):1704-11.

For patients with relapsed or refractory chronic lymphocytic leukemia despite therapy with idelalisib (Zydelig), venetoclax (Venclexta) was associated with relatively high overall response and progression-free survival rates, results of a phase 2 study show.

Among 36 patients with relapsed/refractory CLL who had received idelalisib as their most recent B-cell receptor pathway inhibitor (BCRi), the overall response rate (ORR) was 67%, and median progression-free and overall survival (PFS and OS) had not been reached after 14 months of follow-up, reported Steven Coutre, MD, of Stanford (Calif.) University, and his colleagues.

“[V]enetoclax monotherapy is active and well-tolerated in patients with CLL progression after therapy with idelalisib, including a significant number of patients who also received prior therapy with ibrutinib [Imbruvica]. These results from the first prospective trial in this high-risk population provide evidence that venetoclax should be considered as a treatment option for such patients,” the investigators wrote. The report was published in Blood.

In clinical trials with idelalisib, approximately one-third of patients with CLL experienced disease progression on therapy, and other patients had to discontinue the drug, an inhibitor of the delta isoform of phosphoinositide 3-kinase (PI3K), because of toxicities, the investigators noted.

“The optimal treatment of patients with CLL progressing after idelalisib has not been well characterized,” they wrote. “Outcomes in patients who discontinued idelalisib treatment early are poor, with one retrospective analysis reporting a median overall survival (OS) after idelalisib discontinuation of approximately 2 months (range, 0-10 months).”

Venetoclax, an inhibitor of the apoptotic BCL-2 protein, has been shown to have activity against CLL, including in patients with high-risk features such as the chromosome 17p deletion (del17p), prompting the investigators to evaluate it as a follow-on in patients with relapsed/refractory CLL treated with a B-cell receptor pathway inhibitor.

They reported on the idelalisib cohort in a phase 2 trial in which patients with CLL that progressed on either idelalisib or ibrutinib were subsequently treated with venetoclax. The patients in this analysis included those treated with idelalisib in the main study cohort or an expansion cohort.

Patients were started on venetoclax 20 mg daily, followed by weekly dose escalations to a target of 400 mg daily by week 5, or to a maximum of 600 mg for patients who did not have a response by the week 12 assessment.

The overall response rate – the primary efficacy endpoint – was 67%. There were two complete remissions (CR) and one CR with incomplete bone marrow recovery. The remaining 21 patients with responses had partial responses.

At a median of 14 months of follow-up, neither median PFS, duration of response, or OS had been reached.

The investigator-estimated 12-month PFS rate was 79%.

The most common grade 3 or 4 adverse events were neutropenia in 50% of patients, thrombocytopenia in 25%, and anemia in 17%. There were no cases of clinical tumor lysis syndrome, which has been known to occur when venetoclax is initiated at full dose without a ramp-up.

The most common adverse events of any grade included neutropenia, diarrhea, upper respiratory tract infection, thrombocytopenia, nausea, fatigue, cough, rash, and anemia.

“The low number of CRs reported at the time of analysis may be a result of the follow-up time, particularly for patients in the expansion cohort, as other clinical studies with venetoclax report CR occurring after 1 year on therapy. Patients with prior ibrutinib exposure who had progressed on idelalisib as their most recent therapy before study entry had similar efficacy results,” the investigators wrote.

Genentech and AbbVie funded the study. Dr. Coutre is an advisory board member for both companies and others, and receives institutional funding from AbbVie and others. Multiple coauthors disclosed financial relationships with AbbVie, Genentech, or both, as well as other companies.

SOURCE: Coutre S et al. Blood. 2018;131(15):1704-11.

For patients with relapsed or refractory chronic lymphocytic leukemia despite therapy with idelalisib (Zydelig), venetoclax (Venclexta) was associated with relatively high overall response and progression-free survival rates, results of a phase 2 study show.

Among 36 patients with relapsed/refractory CLL who had received idelalisib as their most recent B-cell receptor pathway inhibitor (BCRi), the overall response rate (ORR) was 67%, and median progression-free and overall survival (PFS and OS) had not been reached after 14 months of follow-up, reported Steven Coutre, MD, of Stanford (Calif.) University, and his colleagues.

“[V]enetoclax monotherapy is active and well-tolerated in patients with CLL progression after therapy with idelalisib, including a significant number of patients who also received prior therapy with ibrutinib [Imbruvica]. These results from the first prospective trial in this high-risk population provide evidence that venetoclax should be considered as a treatment option for such patients,” the investigators wrote. The report was published in Blood.

In clinical trials with idelalisib, approximately one-third of patients with CLL experienced disease progression on therapy, and other patients had to discontinue the drug, an inhibitor of the delta isoform of phosphoinositide 3-kinase (PI3K), because of toxicities, the investigators noted.

“The optimal treatment of patients with CLL progressing after idelalisib has not been well characterized,” they wrote. “Outcomes in patients who discontinued idelalisib treatment early are poor, with one retrospective analysis reporting a median overall survival (OS) after idelalisib discontinuation of approximately 2 months (range, 0-10 months).”

Venetoclax, an inhibitor of the apoptotic BCL-2 protein, has been shown to have activity against CLL, including in patients with high-risk features such as the chromosome 17p deletion (del17p), prompting the investigators to evaluate it as a follow-on in patients with relapsed/refractory CLL treated with a B-cell receptor pathway inhibitor.

They reported on the idelalisib cohort in a phase 2 trial in which patients with CLL that progressed on either idelalisib or ibrutinib were subsequently treated with venetoclax. The patients in this analysis included those treated with idelalisib in the main study cohort or an expansion cohort.

Patients were started on venetoclax 20 mg daily, followed by weekly dose escalations to a target of 400 mg daily by week 5, or to a maximum of 600 mg for patients who did not have a response by the week 12 assessment.

The overall response rate – the primary efficacy endpoint – was 67%. There were two complete remissions (CR) and one CR with incomplete bone marrow recovery. The remaining 21 patients with responses had partial responses.

At a median of 14 months of follow-up, neither median PFS, duration of response, or OS had been reached.

The investigator-estimated 12-month PFS rate was 79%.

The most common grade 3 or 4 adverse events were neutropenia in 50% of patients, thrombocytopenia in 25%, and anemia in 17%. There were no cases of clinical tumor lysis syndrome, which has been known to occur when venetoclax is initiated at full dose without a ramp-up.

The most common adverse events of any grade included neutropenia, diarrhea, upper respiratory tract infection, thrombocytopenia, nausea, fatigue, cough, rash, and anemia.

“The low number of CRs reported at the time of analysis may be a result of the follow-up time, particularly for patients in the expansion cohort, as other clinical studies with venetoclax report CR occurring after 1 year on therapy. Patients with prior ibrutinib exposure who had progressed on idelalisib as their most recent therapy before study entry had similar efficacy results,” the investigators wrote.

Genentech and AbbVie funded the study. Dr. Coutre is an advisory board member for both companies and others, and receives institutional funding from AbbVie and others. Multiple coauthors disclosed financial relationships with AbbVie, Genentech, or both, as well as other companies.

SOURCE: Coutre S et al. Blood. 2018;131(15):1704-11.

Tailoring chemoradiation therapy while minimizing anthracycline exposure produced strong survival results in stage IV favorable histology Wilms tumor (FHWT), according to new results from the Children’s Oncology Group AREN0533 study.

In the new regimen, patients whose isolated lung nodules completely respond to 6 weeks of vincristine/dactinomycin/doxorubicin (DD4A) therapy continue DD4A and forgo lung radiation therapy (RT), explained David B. Dix, MBChB, of British Columbia Children’s Hospital, Vancouver, B.C., and his associates. Incomplete responders and patients with loss of heterozygosity at chromosomes 1p/16q receive lung RT plus boosted chemotherapy consisting of DD4 plus four cycles of cyclophosphamide/etoposide (Regimen M).

Among 133 assessable complete responders who received the DD4A regimen and were followed for a median of 4.7 years, 4-year event-free survival (EFS) was 79.5% (95% confidence interval, 71%-88%) and 4-year overall survival (OS) was 96% (95% CI, 92%-100%), Dr. Dix and his associates wrote. The report was published in the Journal of Clinical Oncology.

Among 159 incomplete responders receiving Regimen M, 4-year EFS was 88.5% (95% CI, 82%-95%) and 4-year OS was 95% (95% CI, 91%-100%). Regimen M produced superior EFS and OS (P less than .001 for both comparisons) than the protocol used in the National Wilms Tumor Study (NWTS) 5 study, in which all patients with lung metastases received DD4A plus RT, regardless of lung nodule response. “These results provide a benchmark for future studies,” Dr. Dix and his associates concluded.

Most patients with FHWT have pulmonary metastases and historically have fared worse than peers with localized disease. Until now, patients have had two main treatment options. The Society of Pediatric Oncology (SIOP) protocol focuses on pre-nephrectomy DD4A and forgoes lung RT if chemotherapy or surgical resection achieves lung nodule CR. Patients in the most recently reported SIOP trial (93-01) received a high cumulative anthracycline dose of 350 mg/m² and had 5-year EFS of 77% and 5-year OS of 87%. The second option – the NWTS protocol – more than halves the cumulative doxorubicin dose (150 mg/m²), but all patients undergo lung RT.

In contrast, the AREN0533 protocol involved cumulative doxorubicin doses of 150 mg/m² for DD4A and 195 mg/m² for Regimen M. Among complete responders, the expected event rate was 15% and the actual rate was 20% (P = .05). Among incomplete responders, observed and expected event rates were 25% and. 12%, respectively (P less than .001). The higher-than-expected event rates might stem from lower chemotherapy doses, but the SIOP study also did not include central image review and may have defined CR less stringently, Dr. Dix and his coinvestigators said.

They concluded that AREN0533 showed “excellent” survival results for patients with CR and that certain late risks of Regimen M – including an increased risk of leukemia from exposure to cyclophosphamide and etoposide – should be balanced against its superior 4-year EFS.

SOURCE: Dix DB et al. J Clin Oncol. 2018 Apr 11. doi: 10.1200/JCO. 2017.77.1931.

Tailoring chemoradiation therapy while minimizing anthracycline exposure produced strong survival results in stage IV favorable histology Wilms tumor (FHWT), according to new results from the Children’s Oncology Group AREN0533 study.

In the new regimen, patients whose isolated lung nodules completely respond to 6 weeks of vincristine/dactinomycin/doxorubicin (DD4A) therapy continue DD4A and forgo lung radiation therapy (RT), explained David B. Dix, MBChB, of British Columbia Children’s Hospital, Vancouver, B.C., and his associates. Incomplete responders and patients with loss of heterozygosity at chromosomes 1p/16q receive lung RT plus boosted chemotherapy consisting of DD4 plus four cycles of cyclophosphamide/etoposide (Regimen M).

Among 133 assessable complete responders who received the DD4A regimen and were followed for a median of 4.7 years, 4-year event-free survival (EFS) was 79.5% (95% confidence interval, 71%-88%) and 4-year overall survival (OS) was 96% (95% CI, 92%-100%), Dr. Dix and his associates wrote. The report was published in the Journal of Clinical Oncology.

Among 159 incomplete responders receiving Regimen M, 4-year EFS was 88.5% (95% CI, 82%-95%) and 4-year OS was 95% (95% CI, 91%-100%). Regimen M produced superior EFS and OS (P less than .001 for both comparisons) than the protocol used in the National Wilms Tumor Study (NWTS) 5 study, in which all patients with lung metastases received DD4A plus RT, regardless of lung nodule response. “These results provide a benchmark for future studies,” Dr. Dix and his associates concluded.

Most patients with FHWT have pulmonary metastases and historically have fared worse than peers with localized disease. Until now, patients have had two main treatment options. The Society of Pediatric Oncology (SIOP) protocol focuses on pre-nephrectomy DD4A and forgoes lung RT if chemotherapy or surgical resection achieves lung nodule CR. Patients in the most recently reported SIOP trial (93-01) received a high cumulative anthracycline dose of 350 mg/m² and had 5-year EFS of 77% and 5-year OS of 87%. The second option – the NWTS protocol – more than halves the cumulative doxorubicin dose (150 mg/m²), but all patients undergo lung RT.

In contrast, the AREN0533 protocol involved cumulative doxorubicin doses of 150 mg/m² for DD4A and 195 mg/m² for Regimen M. Among complete responders, the expected event rate was 15% and the actual rate was 20% (P = .05). Among incomplete responders, observed and expected event rates were 25% and. 12%, respectively (P less than .001). The higher-than-expected event rates might stem from lower chemotherapy doses, but the SIOP study also did not include central image review and may have defined CR less stringently, Dr. Dix and his coinvestigators said.

They concluded that AREN0533 showed “excellent” survival results for patients with CR and that certain late risks of Regimen M – including an increased risk of leukemia from exposure to cyclophosphamide and etoposide – should be balanced against its superior 4-year EFS.

SOURCE: Dix DB et al. J Clin Oncol. 2018 Apr 11. doi: 10.1200/JCO. 2017.77.1931.

Tailoring chemoradiation therapy while minimizing anthracycline exposure produced strong survival results in stage IV favorable histology Wilms tumor (FHWT), according to new results from the Children’s Oncology Group AREN0533 study.

In the new regimen, patients whose isolated lung nodules completely respond to 6 weeks of vincristine/dactinomycin/doxorubicin (DD4A) therapy continue DD4A and forgo lung radiation therapy (RT), explained David B. Dix, MBChB, of British Columbia Children’s Hospital, Vancouver, B.C., and his associates. Incomplete responders and patients with loss of heterozygosity at chromosomes 1p/16q receive lung RT plus boosted chemotherapy consisting of DD4 plus four cycles of cyclophosphamide/etoposide (Regimen M).

Among 133 assessable complete responders who received the DD4A regimen and were followed for a median of 4.7 years, 4-year event-free survival (EFS) was 79.5% (95% confidence interval, 71%-88%) and 4-year overall survival (OS) was 96% (95% CI, 92%-100%), Dr. Dix and his associates wrote. The report was published in the Journal of Clinical Oncology.

Among 159 incomplete responders receiving Regimen M, 4-year EFS was 88.5% (95% CI, 82%-95%) and 4-year OS was 95% (95% CI, 91%-100%). Regimen M produced superior EFS and OS (P less than .001 for both comparisons) than the protocol used in the National Wilms Tumor Study (NWTS) 5 study, in which all patients with lung metastases received DD4A plus RT, regardless of lung nodule response. “These results provide a benchmark for future studies,” Dr. Dix and his associates concluded.

Most patients with FHWT have pulmonary metastases and historically have fared worse than peers with localized disease. Until now, patients have had two main treatment options. The Society of Pediatric Oncology (SIOP) protocol focuses on pre-nephrectomy DD4A and forgoes lung RT if chemotherapy or surgical resection achieves lung nodule CR. Patients in the most recently reported SIOP trial (93-01) received a high cumulative anthracycline dose of 350 mg/m² and had 5-year EFS of 77% and 5-year OS of 87%. The second option – the NWTS protocol – more than halves the cumulative doxorubicin dose (150 mg/m²), but all patients undergo lung RT.

In contrast, the AREN0533 protocol involved cumulative doxorubicin doses of 150 mg/m² for DD4A and 195 mg/m² for Regimen M. Among complete responders, the expected event rate was 15% and the actual rate was 20% (P = .05). Among incomplete responders, observed and expected event rates were 25% and. 12%, respectively (P less than .001). The higher-than-expected event rates might stem from lower chemotherapy doses, but the SIOP study also did not include central image review and may have defined CR less stringently, Dr. Dix and his coinvestigators said.

They concluded that AREN0533 showed “excellent” survival results for patients with CR and that certain late risks of Regimen M – including an increased risk of leukemia from exposure to cyclophosphamide and etoposide – should be balanced against its superior 4-year EFS.

SOURCE: Dix DB et al. J Clin Oncol. 2018 Apr 11. doi: 10.1200/JCO. 2017.77.1931.

WASHINGTON – Successfully treating patients who have treatment-resistant depression (TRD) means leaving acute intervention behind and adopting more chronic remediation techniques, Scott T. Aaronson, MD, said at the annual conference of the Anxiety and Depression Association of America.

“We need to change the paradigm; most of the research is looking at a 6- to 12-week outcome measure,” said Dr. Aaronson, director of the clinical research program at Sheppard Pratt Health System, Baltimore. “These are folks who have been depressed for most of their adult lives, and we don’t tend to take a longer-term perspective when looking at this.”

Treatment-resistant depression, Dr. Aaronson said, can be conceptualized as two levels. The first is failure of two agents or treatments, and the second is a failure of four or more agents – including electroconvulsive therapy. In light of those levels, Dr. Aaronson suggests approaching depression as one would cancer, with different stages of failure determining payment for more expensive treatments.

Courtesy Dr. Scott T. Aaronson

Before planning how best to handle treatment-resistant depression, it is important for psychiatrists to understand its complexity, and address the issues associated with current psychiatric diagnoses, Dr. Aaronson said.

Diagnoses now are based purely on phenomenological analysis rather than biological analysis, he said. “Basically, it’s a room full of people getting together to decide what the diagnostic criteria are,” Dr. Aaronson said. “It’s eminence-based medicine, not evidence-based medicine.”

This approach creates a large gray area in which diagnoses can fall, making it more difficult to distinguish between bipolar and unipolar depression, as well as tough to distinguish psychotic and nonpsychotic illnesses.

If a patient displayed mood instability, for example, but not enough to fit the criteria of bipolar disorder, this scenario would present a dilemma for psychiatrists unable to diagnose the patient as bipolar and unconvinced that it would help to treat the patient as only being depressed, according to an example from Dr. Aaronson.

[email protected]

WASHINGTON – Successfully treating patients who have treatment-resistant depression (TRD) means leaving acute intervention behind and adopting more chronic remediation techniques, Scott T. Aaronson, MD, said at the annual conference of the Anxiety and Depression Association of America.

“We need to change the paradigm; most of the research is looking at a 6- to 12-week outcome measure,” said Dr. Aaronson, director of the clinical research program at Sheppard Pratt Health System, Baltimore. “These are folks who have been depressed for most of their adult lives, and we don’t tend to take a longer-term perspective when looking at this.”

Treatment-resistant depression, Dr. Aaronson said, can be conceptualized as two levels. The first is failure of two agents or treatments, and the second is a failure of four or more agents – including electroconvulsive therapy. In light of those levels, Dr. Aaronson suggests approaching depression as one would cancer, with different stages of failure determining payment for more expensive treatments.

Courtesy Dr. Scott T. Aaronson

Before planning how best to handle treatment-resistant depression, it is important for psychiatrists to understand its complexity, and address the issues associated with current psychiatric diagnoses, Dr. Aaronson said.

Diagnoses now are based purely on phenomenological analysis rather than biological analysis, he said. “Basically, it’s a room full of people getting together to decide what the diagnostic criteria are,” Dr. Aaronson said. “It’s eminence-based medicine, not evidence-based medicine.”

This approach creates a large gray area in which diagnoses can fall, making it more difficult to distinguish between bipolar and unipolar depression, as well as tough to distinguish psychotic and nonpsychotic illnesses.

If a patient displayed mood instability, for example, but not enough to fit the criteria of bipolar disorder, this scenario would present a dilemma for psychiatrists unable to diagnose the patient as bipolar and unconvinced that it would help to treat the patient as only being depressed, according to an example from Dr. Aaronson.

[email protected]

WASHINGTON – Successfully treating patients who have treatment-resistant depression (TRD) means leaving acute intervention behind and adopting more chronic remediation techniques, Scott T. Aaronson, MD, said at the annual conference of the Anxiety and Depression Association of America.

“We need to change the paradigm; most of the research is looking at a 6- to 12-week outcome measure,” said Dr. Aaronson, director of the clinical research program at Sheppard Pratt Health System, Baltimore. “These are folks who have been depressed for most of their adult lives, and we don’t tend to take a longer-term perspective when looking at this.”

Treatment-resistant depression, Dr. Aaronson said, can be conceptualized as two levels. The first is failure of two agents or treatments, and the second is a failure of four or more agents – including electroconvulsive therapy. In light of those levels, Dr. Aaronson suggests approaching depression as one would cancer, with different stages of failure determining payment for more expensive treatments.

Courtesy Dr. Scott T. Aaronson

Before planning how best to handle treatment-resistant depression, it is important for psychiatrists to understand its complexity, and address the issues associated with current psychiatric diagnoses, Dr. Aaronson said.

Diagnoses now are based purely on phenomenological analysis rather than biological analysis, he said. “Basically, it’s a room full of people getting together to decide what the diagnostic criteria are,” Dr. Aaronson said. “It’s eminence-based medicine, not evidence-based medicine.”

This approach creates a large gray area in which diagnoses can fall, making it more difficult to distinguish between bipolar and unipolar depression, as well as tough to distinguish psychotic and nonpsychotic illnesses.

If a patient displayed mood instability, for example, but not enough to fit the criteria of bipolar disorder, this scenario would present a dilemma for psychiatrists unable to diagnose the patient as bipolar and unconvinced that it would help to treat the patient as only being depressed, according to an example from Dr. Aaronson.

[email protected]

Clinical Neurology News editorial advisory board member Jonathan L. Carter, MD, scoured the pages of the American Academy of Neurology’s annual meeting program for his “top picks” in multiple sclerosis at this year’s meeting.

NFLCs in serum as a biomarker for MS and treatment response. Multiple abstracts explore the use of NFLCs as a marker for disease progression and response to MS therapies, including:

• Hot Topics Plenary Session presentation: “Monitoring Multiple Sclerosis Using Blood Neurofilament Light Protein” by Jens Kuhle, MD.
• P5.036, Serum and CSF Neurofilament Light Chain levels normalise following Bone Marrow Transplant in MS Patients.
• S24.002, Interim Analysis of the OBOE (Ocrelizumab Biomarker Outcome Evaluation) Study in Multiple Sclerosis (MS).
• S24.003, Serum Neurofilament Light (NfL): Towards a Blood Test for Prognosis and Disease/Treatment Monitoring in Multiple Sclerosis Patients.
• S24.004, Long-term Prognosis of Disease Evolution and Evidence for Sustained Fingolimod Treatment Effect by Blood Neurofilament Light in RRMS Patients.
• S24.007, Including Blood Neurofilament Light Chain in the NEDA Concept in Relapsing Remitting Multiple Sclerosis Trials.
• S8.006, Siponimod Reduces Neurofilament Light Chain Blood Levels in Secondary Progressive Multiple Sclerosis Patients.

Cognitive function as an outcome measure in MS clinical trials. Several abstracts examine cognition as an outcome measure in clinical trials and show slowing of cognitive worsening in patients on MS disease-modifying therapies:

• S44.004, Impact of Siponimod on Cognition in Patients With Secondary Progressive Multiple Sclerosis: Results From Phase 3 EXPAND Study.
• S44.005, Time to Cognitive Worsening in Patients With Relapsing Multiple Sclerosis in Ocrelizumab Phase 3 Trials.
• S44.007, Benchmarks of Cognitive Performance in a Large, Representative Patient Population.

Improved disability outcome measures and predictors of disability in MS. Several abstracts assess novel disability outcome measures and neuroimaging techniques to better predict progression of clinical disability:

• P4.380, Overall Response Score: A Novel Disability Endpoint That Allows for the Integrated Assessment of Improvement and Worsening over Time in Patients with MS.
• S47.001, Longitudinal Changes in Quantitative Spinal Cord MRI in Multiple Sclerosis Patients: Results of a 5-year Study.
• P6.354, Effect of Fingolimod 0.5 mg/day versus Placebo on Two Newly Developed Expanded Disability Status Scale (EDSS) Subscales for Patients with Relapsing Remitting MS: EDSS Factor Analysis.

Is treatment response in MS an age-dependent or relapse-driven phenomenon, and is it safe to discontinue MS therapies with advancing age? Several abstracts address this question:

• S47.004, Meta-Analysis of the Age-Dependent Efficacy of Multiple Sclerosis Treatments.
• S8.005, Uncoupling the Impact on Relapses and Disability Progression: Siponimod in Relapsing and Nonrelapsing Patients With Secondary Progressive Multiple Sclerosis in the Phase 3 EXPAND Study.
• S8.008, Discontinuation of Disease Modifying Therapies in Stable MS Patients is Associated with Disability Progression Regardless of Age.

Neuromyelitis optica spectrum disorders and MS mimics. Multiple abstracts explore the differences between neuromyelitis optica spectrum disorder because of aquaporin-4 versus myelin oligodendrocyte glycoprotein antibodies; describe unique features of another recently described autoimmune disorder, autoimmune GFAP astrocytopathy; and explore the differential diagnosis of idiopathic transverse myelitis:

• S13.002, Clinical Characteristics of MOG and AQP associated Neuromyelitis Optica Spectrum Disorder (NMOSD) in Adults, through S13.008, It’s Not All Transverse Myelitis: The Differential Diagnosis of Spinal Cord Myelopathy.
• P6.409, The Mayo Clinic Glial Autoimmunity Study: Glial autoantibody (AQP4/MOG/GFAP) serostatus in recurrent longitudinally extensive transverse myelitis.
• P6.417, Evaluation of idiopathic transverse myelitis revealing specific myelopathy diagnoses.
• S6.003, Brain and Spinal Cord Imaging Features in Neuromyelitis Optica Spectrum Disorders.

Updated safety and efficacy data for recently approved or investigational MS therapies. Multiple abstracts report updated safety and efficacy data from MS clinical trials of ozanimod, ocrelizumab (Ocrevus), and hematopoietic stem cell transplantation:

• Clinical Trials Plenary Session presentation: “A Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis” by Robert J. Fox, MD.
• Contemporary Clinical Issues Plenary Session presentation: “Biosimilars and Nonbiologic Complex Drugs” by Jeffrey Allan Cohen, MD.
• S6.002, Brain MRI Activity and Atrophy Measures in Patients Receiving Continuous Ocrelizumab or Switching From Interferon Beta-1a to Ocrelizumab Therapy in the Open-Label Extension Period of the Phase 3 Trials of Ocrelizumab in Patients With Relapsing Multiple Sclerosis.
• P3.410, Clinical and Magnetic Resonance Imaging Results From RADIANCE Part B, a Multicenter, Randomized, Double-Blind, Phase 3 Trial of Ozanimod Versus Intramuscular Interferon beta-1a in Relapsing Multiple Sclerosis (RMS).
• P3.396, Ozanimod Demonstrates Efficacy and Safety in a Multicenter, Randomized, Double-Blind, Double-Dummy, Active-Controlled Phase 3 Trial of Relapsing Multiple Sclerosis (SUNBEAM).
• S36.001, Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in Patients With Relapsing and Primary Progressive Multiple Sclerosis.
• S36.004, Nonmyeloablative hematopoietic stem cell transplantation (HSCT) is superior to disease modifying drug (DMD) treatment in highly active Relapsing Remitting Multiple Sclerosis (RRMS): interim results of the Multiple Sclerosis International Stem cell Transplant (MIST) Randomized Trial.
• S36.005, Efficacy of Ozanimod Versus Interferon beta-1a by Prior Treatment and Baseline Disability in Two Multicenter, Randomized, Double-Blind, Parallel-Group, Active-Controlled, Double-Dummy Phase 3 Studies in Relapsing Multiple Sclerosis (SUNBEAM and RADIANCE Part B).
• S36.006, Safety of Ozanimod Versus Interferon beta-1a in Two Multicenter, Randomized, Double-Blind, Parallel-Group, Active-Controlled, Double-Dummy Phase 3 Studies in Relapsing Multiple Sclerosis (SUNBEAM and RADIANCE Part B).

New thoughts on MS pathogenesis.

• Frontiers in Neuroscience Plenary Session presentation: “Pediatric MS: A Unique Window into Environmental and Genetic Risk Factors for MS” by Emmanuelle Waubant, MD.

Dr. Carter has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alder Pharmaceuticals. He has received research support from Roche/Genentech and MedDay Pharmaceuticals.
 

Clinical Neurology News editorial advisory board member Jonathan L. Carter, MD, scoured the pages of the American Academy of Neurology’s annual meeting program for his “top picks” in multiple sclerosis at this year’s meeting.

NFLCs in serum as a biomarker for MS and treatment response. Multiple abstracts explore the use of NFLCs as a marker for disease progression and response to MS therapies, including:

• Hot Topics Plenary Session presentation: “Monitoring Multiple Sclerosis Using Blood Neurofilament Light Protein” by Jens Kuhle, MD.
• P5.036, Serum and CSF Neurofilament Light Chain levels normalise following Bone Marrow Transplant in MS Patients.
• S24.002, Interim Analysis of the OBOE (Ocrelizumab Biomarker Outcome Evaluation) Study in Multiple Sclerosis (MS).
• S24.003, Serum Neurofilament Light (NfL): Towards a Blood Test for Prognosis and Disease/Treatment Monitoring in Multiple Sclerosis Patients.
• S24.004, Long-term Prognosis of Disease Evolution and Evidence for Sustained Fingolimod Treatment Effect by Blood Neurofilament Light in RRMS Patients.
• S24.007, Including Blood Neurofilament Light Chain in the NEDA Concept in Relapsing Remitting Multiple Sclerosis Trials.
• S8.006, Siponimod Reduces Neurofilament Light Chain Blood Levels in Secondary Progressive Multiple Sclerosis Patients.

Cognitive function as an outcome measure in MS clinical trials. Several abstracts examine cognition as an outcome measure in clinical trials and show slowing of cognitive worsening in patients on MS disease-modifying therapies:

• S44.004, Impact of Siponimod on Cognition in Patients With Secondary Progressive Multiple Sclerosis: Results From Phase 3 EXPAND Study.
• S44.005, Time to Cognitive Worsening in Patients With Relapsing Multiple Sclerosis in Ocrelizumab Phase 3 Trials.
• S44.007, Benchmarks of Cognitive Performance in a Large, Representative Patient Population.

Improved disability outcome measures and predictors of disability in MS. Several abstracts assess novel disability outcome measures and neuroimaging techniques to better predict progression of clinical disability:

• P4.380, Overall Response Score: A Novel Disability Endpoint That Allows for the Integrated Assessment of Improvement and Worsening over Time in Patients with MS.
• S47.001, Longitudinal Changes in Quantitative Spinal Cord MRI in Multiple Sclerosis Patients: Results of a 5-year Study.
• P6.354, Effect of Fingolimod 0.5 mg/day versus Placebo on Two Newly Developed Expanded Disability Status Scale (EDSS) Subscales for Patients with Relapsing Remitting MS: EDSS Factor Analysis.

Is treatment response in MS an age-dependent or relapse-driven phenomenon, and is it safe to discontinue MS therapies with advancing age? Several abstracts address this question:

• S47.004, Meta-Analysis of the Age-Dependent Efficacy of Multiple Sclerosis Treatments.
• S8.005, Uncoupling the Impact on Relapses and Disability Progression: Siponimod in Relapsing and Nonrelapsing Patients With Secondary Progressive Multiple Sclerosis in the Phase 3 EXPAND Study.
• S8.008, Discontinuation of Disease Modifying Therapies in Stable MS Patients is Associated with Disability Progression Regardless of Age.

Neuromyelitis optica spectrum disorders and MS mimics. Multiple abstracts explore the differences between neuromyelitis optica spectrum disorder because of aquaporin-4 versus myelin oligodendrocyte glycoprotein antibodies; describe unique features of another recently described autoimmune disorder, autoimmune GFAP astrocytopathy; and explore the differential diagnosis of idiopathic transverse myelitis:

• S13.002, Clinical Characteristics of MOG and AQP associated Neuromyelitis Optica Spectrum Disorder (NMOSD) in Adults, through S13.008, It’s Not All Transverse Myelitis: The Differential Diagnosis of Spinal Cord Myelopathy.
• P6.409, The Mayo Clinic Glial Autoimmunity Study: Glial autoantibody (AQP4/MOG/GFAP) serostatus in recurrent longitudinally extensive transverse myelitis.
• P6.417, Evaluation of idiopathic transverse myelitis revealing specific myelopathy diagnoses.
• S6.003, Brain and Spinal Cord Imaging Features in Neuromyelitis Optica Spectrum Disorders.

Updated safety and efficacy data for recently approved or investigational MS therapies. Multiple abstracts report updated safety and efficacy data from MS clinical trials of ozanimod, ocrelizumab (Ocrevus), and hematopoietic stem cell transplantation:

• Clinical Trials Plenary Session presentation: “A Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis” by Robert J. Fox, MD.
• Contemporary Clinical Issues Plenary Session presentation: “Biosimilars and Nonbiologic Complex Drugs” by Jeffrey Allan Cohen, MD.
• S6.002, Brain MRI Activity and Atrophy Measures in Patients Receiving Continuous Ocrelizumab or Switching From Interferon Beta-1a to Ocrelizumab Therapy in the Open-Label Extension Period of the Phase 3 Trials of Ocrelizumab in Patients With Relapsing Multiple Sclerosis.
• P3.410, Clinical and Magnetic Resonance Imaging Results From RADIANCE Part B, a Multicenter, Randomized, Double-Blind, Phase 3 Trial of Ozanimod Versus Intramuscular Interferon beta-1a in Relapsing Multiple Sclerosis (RMS).
• P3.396, Ozanimod Demonstrates Efficacy and Safety in a Multicenter, Randomized, Double-Blind, Double-Dummy, Active-Controlled Phase 3 Trial of Relapsing Multiple Sclerosis (SUNBEAM).
• S36.001, Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in Patients With Relapsing and Primary Progressive Multiple Sclerosis.
• S36.004, Nonmyeloablative hematopoietic stem cell transplantation (HSCT) is superior to disease modifying drug (DMD) treatment in highly active Relapsing Remitting Multiple Sclerosis (RRMS): interim results of the Multiple Sclerosis International Stem cell Transplant (MIST) Randomized Trial.
• S36.005, Efficacy of Ozanimod Versus Interferon beta-1a by Prior Treatment and Baseline Disability in Two Multicenter, Randomized, Double-Blind, Parallel-Group, Active-Controlled, Double-Dummy Phase 3 Studies in Relapsing Multiple Sclerosis (SUNBEAM and RADIANCE Part B).
• S36.006, Safety of Ozanimod Versus Interferon beta-1a in Two Multicenter, Randomized, Double-Blind, Parallel-Group, Active-Controlled, Double-Dummy Phase 3 Studies in Relapsing Multiple Sclerosis (SUNBEAM and RADIANCE Part B).

New thoughts on MS pathogenesis.

• Frontiers in Neuroscience Plenary Session presentation: “Pediatric MS: A Unique Window into Environmental and Genetic Risk Factors for MS” by Emmanuelle Waubant, MD.

Dr. Carter has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alder Pharmaceuticals. He has received research support from Roche/Genentech and MedDay Pharmaceuticals.
 

Clinical Neurology News editorial advisory board member Jonathan L. Carter, MD, scoured the pages of the American Academy of Neurology’s annual meeting program for his “top picks” in multiple sclerosis at this year’s meeting.

NFLCs in serum as a biomarker for MS and treatment response. Multiple abstracts explore the use of NFLCs as a marker for disease progression and response to MS therapies, including:

• Hot Topics Plenary Session presentation: “Monitoring Multiple Sclerosis Using Blood Neurofilament Light Protein” by Jens Kuhle, MD.
• P5.036, Serum and CSF Neurofilament Light Chain levels normalise following Bone Marrow Transplant in MS Patients.
• S24.002, Interim Analysis of the OBOE (Ocrelizumab Biomarker Outcome Evaluation) Study in Multiple Sclerosis (MS).
• S24.003, Serum Neurofilament Light (NfL): Towards a Blood Test for Prognosis and Disease/Treatment Monitoring in Multiple Sclerosis Patients.
• S24.004, Long-term Prognosis of Disease Evolution and Evidence for Sustained Fingolimod Treatment Effect by Blood Neurofilament Light in RRMS Patients.
• S24.007, Including Blood Neurofilament Light Chain in the NEDA Concept in Relapsing Remitting Multiple Sclerosis Trials.
• S8.006, Siponimod Reduces Neurofilament Light Chain Blood Levels in Secondary Progressive Multiple Sclerosis Patients.

Cognitive function as an outcome measure in MS clinical trials. Several abstracts examine cognition as an outcome measure in clinical trials and show slowing of cognitive worsening in patients on MS disease-modifying therapies:

• S44.004, Impact of Siponimod on Cognition in Patients With Secondary Progressive Multiple Sclerosis: Results From Phase 3 EXPAND Study.
• S44.005, Time to Cognitive Worsening in Patients With Relapsing Multiple Sclerosis in Ocrelizumab Phase 3 Trials.
• S44.007, Benchmarks of Cognitive Performance in a Large, Representative Patient Population.

Improved disability outcome measures and predictors of disability in MS. Several abstracts assess novel disability outcome measures and neuroimaging techniques to better predict progression of clinical disability:

• P4.380, Overall Response Score: A Novel Disability Endpoint That Allows for the Integrated Assessment of Improvement and Worsening over Time in Patients with MS.
• S47.001, Longitudinal Changes in Quantitative Spinal Cord MRI in Multiple Sclerosis Patients: Results of a 5-year Study.
• P6.354, Effect of Fingolimod 0.5 mg/day versus Placebo on Two Newly Developed Expanded Disability Status Scale (EDSS) Subscales for Patients with Relapsing Remitting MS: EDSS Factor Analysis.

Is treatment response in MS an age-dependent or relapse-driven phenomenon, and is it safe to discontinue MS therapies with advancing age? Several abstracts address this question:

• S47.004, Meta-Analysis of the Age-Dependent Efficacy of Multiple Sclerosis Treatments.
• S8.005, Uncoupling the Impact on Relapses and Disability Progression: Siponimod in Relapsing and Nonrelapsing Patients With Secondary Progressive Multiple Sclerosis in the Phase 3 EXPAND Study.
• S8.008, Discontinuation of Disease Modifying Therapies in Stable MS Patients is Associated with Disability Progression Regardless of Age.

Neuromyelitis optica spectrum disorders and MS mimics. Multiple abstracts explore the differences between neuromyelitis optica spectrum disorder because of aquaporin-4 versus myelin oligodendrocyte glycoprotein antibodies; describe unique features of another recently described autoimmune disorder, autoimmune GFAP astrocytopathy; and explore the differential diagnosis of idiopathic transverse myelitis:

• S13.002, Clinical Characteristics of MOG and AQP associated Neuromyelitis Optica Spectrum Disorder (NMOSD) in Adults, through S13.008, It’s Not All Transverse Myelitis: The Differential Diagnosis of Spinal Cord Myelopathy.
• P6.409, The Mayo Clinic Glial Autoimmunity Study: Glial autoantibody (AQP4/MOG/GFAP) serostatus in recurrent longitudinally extensive transverse myelitis.
• P6.417, Evaluation of idiopathic transverse myelitis revealing specific myelopathy diagnoses.
• S6.003, Brain and Spinal Cord Imaging Features in Neuromyelitis Optica Spectrum Disorders.

Updated safety and efficacy data for recently approved or investigational MS therapies. Multiple abstracts report updated safety and efficacy data from MS clinical trials of ozanimod, ocrelizumab (Ocrevus), and hematopoietic stem cell transplantation:

• Clinical Trials Plenary Session presentation: “A Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis” by Robert J. Fox, MD.
• Contemporary Clinical Issues Plenary Session presentation: “Biosimilars and Nonbiologic Complex Drugs” by Jeffrey Allan Cohen, MD.
• S6.002, Brain MRI Activity and Atrophy Measures in Patients Receiving Continuous Ocrelizumab or Switching From Interferon Beta-1a to Ocrelizumab Therapy in the Open-Label Extension Period of the Phase 3 Trials of Ocrelizumab in Patients With Relapsing Multiple Sclerosis.
• P3.410, Clinical and Magnetic Resonance Imaging Results From RADIANCE Part B, a Multicenter, Randomized, Double-Blind, Phase 3 Trial of Ozanimod Versus Intramuscular Interferon beta-1a in Relapsing Multiple Sclerosis (RMS).
• P3.396, Ozanimod Demonstrates Efficacy and Safety in a Multicenter, Randomized, Double-Blind, Double-Dummy, Active-Controlled Phase 3 Trial of Relapsing Multiple Sclerosis (SUNBEAM).
• S36.001, Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in Patients With Relapsing and Primary Progressive Multiple Sclerosis.
• S36.004, Nonmyeloablative hematopoietic stem cell transplantation (HSCT) is superior to disease modifying drug (DMD) treatment in highly active Relapsing Remitting Multiple Sclerosis (RRMS): interim results of the Multiple Sclerosis International Stem cell Transplant (MIST) Randomized Trial.
• S36.005, Efficacy of Ozanimod Versus Interferon beta-1a by Prior Treatment and Baseline Disability in Two Multicenter, Randomized, Double-Blind, Parallel-Group, Active-Controlled, Double-Dummy Phase 3 Studies in Relapsing Multiple Sclerosis (SUNBEAM and RADIANCE Part B).
• S36.006, Safety of Ozanimod Versus Interferon beta-1a in Two Multicenter, Randomized, Double-Blind, Parallel-Group, Active-Controlled, Double-Dummy Phase 3 Studies in Relapsing Multiple Sclerosis (SUNBEAM and RADIANCE Part B).

New thoughts on MS pathogenesis.

• Frontiers in Neuroscience Plenary Session presentation: “Pediatric MS: A Unique Window into Environmental and Genetic Risk Factors for MS” by Emmanuelle Waubant, MD.

Dr. Carter has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alder Pharmaceuticals. He has received research support from Roche/Genentech and MedDay Pharmaceuticals.