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thrombocytopenia ( n = 3 each ), followed by hyperbilirubinemia , neutropenia , lung infection , and pneumonia ( n = 2 each ).
According to the investigators , the incidence of enasidenib-related indirect bilirubin elevations and grade 1 to 2 gastrointestinal AEs in this study were most likely a result of “ off-target inhibition of the UGT1A1 enzyme .”
At data cutoff , 15 of the ivosidenibtreated patients ( 65 %) and three of the enasidenib-treated patients ( 50 %) responded to treatment . Responses included :
• complete remission ( CR ): 10 patients ( 44 %) in the ivosidenib arm and 3 patients ( 50 %) in the enasidenib arm
• CR with incomplete count recovery : 5 ( 22 %) and 0
In addition , three participants in the ivosidenib group and one in the enasidenib group had morphologic leukemia-free state . To measure depth of response , the researchers also evaluated IDH clearance in 27 patients with sequencing data available . IDH1 mutation clearance was observed in seven of 21 ivosidenib-treated patients and three of the six enasidenib-treated patients – all of whom had responded to treatment .
A limitation of this early-phase study includes its relatively small sample size , which may reduce generalizability of the findings to the larger population of patients with newly diagnosed AML . There also was no comparison arm .
Based on these initial findings , the researchers are now enrolling patients in the phase II and III AGILE study portions , which are evaluating outcomes associated with enasidenib plus azacitidine and ivosidenib plus azacitidine , respectively .
Dr . DiNardo added that she would like to see further research to answer the questions of “ whether development of IDH minimal residual disease – negative status can be used to predict durable responses , and whether certain computations are predictive of response or resistance to this combination .”
Dr . DiNardo reports financial relationships with Celgene and Agios , the manufacturer of ivosidenib and enasidenib .
REFERENCE DiNardo CD , Stein AS , Stein EM , et al . Mutant IDH ( MIDH ) inhibitors , ivosidenib or enasidenib , with azacitidine ( AZA ) in patients with acute myeloid leukemia ( AML ). Abstract # S1562 . Presented at the EHA 23rd Congress , June 17 , 2018 ; Stockholm , Sweden .
Attendees gather at the 23rd EHA Congress .
Cardiac Biomarkers Predict Quality of Life in Patients With Light-Chain Amyloidosis
In a study presented at the 23rd Congress of the European Hematology Association , researchers demonstrated a relationship between B-type natriuretic peptide ( BNP ) and N-terminal pro B-type natriuretic peptide ( NTproBNP ) and health-related quality of life ( HRQoL ) in patients with light-chain ( AL ) amyloidosis . These cardiac measures are “ commonly used to monitor disease progression and response to treatment among patients with cardiac involvement from AL amyloidosis ,” reported the authors , led by Kristen L . McCausland , PhD , MPH , of Optum in Providence , Rhode Island . This study ’ s findings suggest that BNP and NT-proBNP could act as surrogate measures for HRQoL and disease burden in this patient population .
“ This study is an important first step in examining the relationship between changes in cardiac biomarkers , particularly NT-proBNP , and HRQoL in patients with AL amyloidosis ,” said study researcher and presenter Tiffany P . Quock , PhD , of Prothena Biosciences in San Francisco . “ Patients with AL amyloidosis who experienced a self-reported cardiac response to treatment reported better HRQoL as compared to patients without a cardiac treatment response .”
Drs . McCausland , Quock , and colleagues examined the relationship between cardiac biomarkers and patients ’ HRQoL in two data sources : a community-based sample ( n = 108 ) and clinical sample of patients with AL amyloidosis receiving hospital care ( n = 95 ).
HRQoL was measured by patient-reported surveys ( the 36-Item Short Form Health Survey [ SF-36 ] and a short form of the Kansas City Cardiomyopathy Questionnaire [ KCCQ-12 ]), then compared between patients with and without declines in BNP and NT-proBNP of ≥30 percent . Individuals in the community-based sample who reported an NT-proBNP response ( n = 75 ) demonstrated significantly greater HRQoL , compared with individuals without a response ( n = 33 ), based on all SF-36 and KCCQ- 12 scores ( p < 0.05 for all ). However , for those without an NT-proBNP response , scores on the SF-36 were similar to benchmark scores for patients with congestive heart failure . The researchers also identified potential long-term associations between cardiac biomarker changes and HRQoL score changes in the analysis of the clinical sample .
“ To overcome some of the study ’ s limitations , we also conducted exploratory analyses based on a clinical sample ,” said Dr . McCausland . “ However further longitudinal research using NT-proBNP lab values from a larger sample is warranted .” Additionally , considering this study used self-report to identify cardiac response to treatment , she noted that future studies should use objective measures to evaluate treatment response in AL amyloidosis .
Based on these findings , Dr . McCausland stated that clinicians should rely on a combination of patient-reported outcomes and laboratory reports for identifying complementary and critical data on the well-being of patients with AL amyloidosis . “ Despite reporting a cardiac response to treatment , treatment responders still experienced significant deficits in HRQoL , particularly in aspects related to physical health ,” she said . “ Using patient-reported outcomes in the clinical setting may help clinicians identify patients with these deficits in HRQoL and recommend supportive therapies .”
Corresponding authors report financial relationships with Prothena Biosciences , which supported the study .
REFERENCE McCausland KL , Guthrie S , Quock T , et al . Improvements in cardiac biomarkers are associated with better health-related quality of life in patients with light chain amyloidosis . Abstract # S147 . Presented at the 23rd Congress of the European Hematology Association , June 15 , 2018 ; Stockholm , Sweden .
Bispecific Antibody AMV564 Active in Relapsed and Refractory AML
Treatment with the CD33 / CD3 bivalent , bispecific antibody AMV564 demonstrated clinical activity in patients with relapsed and refractory acute myeloid leukemia ( AML ) with a tolerable safety profile , according to results from a first-in-human trial presented by lead investigator Peter Westervelt , MD , PhD , at the 23rd Congress of the European Hematology Association .
Even at low doses ( ≤50 mcg ), the agent showed evidence of reducing bone marrow ( BM ) blasts , activating T cells , and reducing spleen size , the researchers reported . “ AMV564 has distinctive pharmacokinetic features , compared with smaller monovalent bispecific agents ,” Dr . Westervelt , from the Washington University School of Medicine in St . Louis , told ASH Clinical News .
“ In this ongoing trial , we observed a prolonged half-life of approximately two days that was associated with gradual drug accumulation and manageable cytokine release syndrome ( CRS ) at higher doses .”
The early-phase trial enrolled 17 patients with AML who had received one or two prior induction regimens consisting of a hypomethylating agent or standard anthracyclinebased therapy . Most ( 83 %) had secondary AML and / or adverse cytogenetics and a history of receiving at least one salvage regimen ( 75 %). Seven patients also had received one or more intensive chemotherapybased regimens ( 58 %).
Over 14 consecutive days , the investigators administered AMV564 through continuous intravenous infusion for up to two cycles of induction at the following dosing levels :
• 0.5 mcg / day
• 1.5 mcg / day
• 5.0 mcg / day
• 15 mcg / day
• 50 mcg / day
The most common grade 1 or 2 adverse events ( AEs ) included peripheral edema , pyrexia , cough , nausea , pneumonia , and fatigue . During and following therapy , there were no reports of treatment-related grade ≥3 AEs through the 50-mcg dose . Although four patients ( 20 %) reported grade 3 febrile neutropenia , the
36 ASH Clinical News August 2018