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Rebecca Olin, MD, MS

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IDH2 Inhibition Plus Azacitidine in IDH2 -Mutant AML

By: Lauren Harrison, MS
Posted: Sunday, March 1, 2020

Combining the small-molecule inhibitor of mutant isocitrate dehydrogenase 2 (IDH2) enasidenib with the hypomethylating agent azacitidine appears to be associated with significantly improved complete remission and overall response rate in patients with IDH2-mutant acute myeloid leukemia (AML) compared with azacitidine alone. Courtney D. DiNardo, MD, MSc, of The University of Texas MD Anderson Cancer Center, Houston, presented these findings on behalf of colleagues at the 2019 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 643) and published in the journal Blood.

From October 2016 through August 2018, 101 patients with IDH2-mutant AML who were ineligible to receive intensive chemotherapy were recruited to the study. Patients were randomly assigned 2:1 to receive either enasidenib plus azacitidine or azacitidine alone in repeated 28-day cycles.

Among this population, 78% of patients in the enasidenib-plus-azacitidine arm and 90% in the azacitidine-alone arm had intermediate-risk cytogenetics at data cutoff. In addition, 18% and 10% of patients had poor-risk cytogenetics in the combination and monotherapy groups, respectively.

The overall response rate was 68% in the group receiving azacitidine plus enasidenib and 42% in the group receiving azacytidine alone; the complete remission rates were 50% and 12%, respectively. The maximal IDH2-mutant suppression from baseline was greater in the combination group than in the azacitidine-alone group (median–69.3% and –14.1%, respectively).

By February 2019 (data cutoff), 39 patients were still receiving their randomized therapy. Common reasons for treatment discontinuation included death (31% with enasidenib plus azacitidine, 27% with azacitidine) and patient decision (4% with enasidenib plus azacitidine, 12% with azacitidine). Grade 3 or 4 treatment-related adverse events occurring in the enasidenib-plus-azacitidine group were neutropenia (34%), thrombocytopenia (24%), anemia (21%), febrile neutropenia (12%), and IDH differentiation syndrome (10%), and they occurred at rates of 19%, 19%, 22%, 3%, and 0%, respectively in patients in the azacitidine-alone arm.

Disclosure: For full disclosures of the study authors, visit ashpublications.org.


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