Mutant IDH (mIDH) inhibitors, ivosidenib or enasidenib, with azacitidine (AZA) in patients with acute myeloid leukemia (AML).

7042Background: Ivosidenib (IVO; AG-120) and enasidenib (ENA; AG-221) are oral inhibitors of mIDH1 and mIDH2 proteins. In vitro, mIDH inhibitor + AZA combinations enhance cell differentiation and apoptosis. We report results of an ongoing phase 1b/2 study of mIDH inhibitors + AZA in patients (pts) with newly diagnosed (ND) AML (NCT02677922). Methods: Adult pts with mIDH ND-AML ineligible for intensive treatment (Tx) receive continuous IVO (mIDH1) 500 mg or ENA (mIDH2) 100 or 200 mg QD, plus SC AZA 75 mg/m2 x 7d, in repeated 28d cycles. Response is defined by IWG 2003 AML criteria. Results: At data cutoff (Sep 1, 2017) 17 pts had received IVO 500 mg (n = 11) or ENA 100 mg (3) or 200 mg (3) + AZA in the phase 1b portion of the study; 11 were ongoing. IVO: Median age was 76 yrs. Median number of Tx cycles was 3 (range 1-13).Three pts discontinued Tx, 2 due to progressive disease (PD).AEs in ≥4 pts (any grade) were nausea (n = 8), constipation (6), fatigue (5) and diarrhea (4). Grade 3-4 hematological AEs (Ta...