Tolerability and Outcomes With Serial Cycles of 28 Days of Venetoclax in Newly Diagnosed Patients With Acute Myeloid Leukemia

The standard of care for newly-diagnosed unfit patients with acute myeloid leukemia (AML) is venetoclax (VEN) with azacitidine (AZA). In the phase 3 trial, before remission, AZA was given with 28 days of VEN. This regimen is myelosuppressive; therefore, many decrease VEN duration before and/or after initial response assessment. We report our center's outcomes administering 28 days of VEN preremission, and in most cases, postremission, relying on other strategies to reduce cytopenias. All newly-diagnosed patients with AML treated outside of a clinical trial with VEN/AZA for > 7 days at our center from 2018 to 2024 were reviewed. 134 patients met inclusion criteria; median age was 70 years (interquartile range [IQR] 64-76), 57% male, and 63% had European LeukemiaNet adverse risk AML (85/134). Overall response rate (including complete remission and complete remission with incomplete hematologic recovery) was 87/134 (64.9%). Median cycles completed was 2 (IQR 1-3, range 0-26), with 117 (87%) completing ≥ 1 cycle with a response assessment. Median duration of cycles 1-5 was 42 days. Median overall survival was 381 days. Prior to response assessment, 113/117 (96.6%) received 28 days of VEN. Postresponse, 17/81 (21.0%) had a VEN reduction (in duration or dose). Grade ≥ 3 neutropenia or thrombocytopenia was higher in cycle 1 than in similar studies, without differences in transfusion needs or infectious complications. Hematologic toxicities improved with subsequent cycles. Serial cycles with 28 days of VEN can be administered pre- and postremission with higher early myelosuppression but similar transfusion and infection rates compared to studies of reduced VEN duration.