Venetoclax and azacitidine for younger acute myeloid leukemia patients independent of fitness for intensive chemotherapy.

Venetoclax (ven)+azacitidine (aza) is the standard of care for newly-diagnosed acute myeloid leukemia (AML) patients who are not candidates for intensive chemotherapy (IC). Because prognostic factors for ven/aza and IC differ, an AML patient fit for IC may derive more benefit from ven/aza. We therefore designed a trial for younger, newly-diagnosed AML patients with non-favorable risk disease to receive ven/aza regardless of "fitness" for IC. We aimed to understand toxicity and efficacy in this population, and retrospectively compared outcomes to matched IC patients. Newly-diagnosed non-favorable risk patients ≤60 were enrolled and received ven, dose escalated to 600mg/dailyx28 days, with aza 75mg/m2x7 days on a 28-day cycle. Subjects were encouraged to move expeditiously to allogeneic stem cell transplant (ASCT) in first remission. Thirty-six subjects enrolled. Median age was 49 (22-59). Grade ≥3 neutropenia(42%), anemia(33%), thrombocytopenia(53%) and febrile neutropenia(36%) were common. The overall response rate (ORR) was 25/36 (69%) with 19 (53%) complete remissions; 68% of responders achieved MRD-negativity. Most subjects (53%) bridged to ASCT, and the majority of non-responders were successfully salvaged with IC. The median progressionfree- survival (PFS) and overall survival (OS) have not been reached (median follow-up 2.9 years). Compared to IC matched controls, the ORR, ASCT rate and PFS were significantly improved (69% vs 44% [p=0.0495], 53% vs 28% [p-0.0290] and not reached vs 60.8 months [p=0.007]). Hospital days, transfusions and infectious complications were significantly reduced for ven/aza subjects. Ven/aza is feasible for newly-diagnosed, younger, non-favorable risk AML patients, and appears at least as effective as IC.