Tolerability and outcomes with serial cycles of 28 days of venetoclax in newly diagnosed patients with AML.

e18527 Background: The standard of care for newly-diagnosed patients with acute myeloid leukemia (AML) unable to tolerate intensive induction chemotherapy is venetoclax (ven) with azacitidine (aza). In the definitive phase 3 clinical trial, aza was given with 28 days of ven during serial cycles. This regimen is myelosuppressive; as a result, many have adopted a strategy to decrease ven duration prior to the initial response assessment. In contrast, and in accordance with the label, our institution continues to administer 28 days of ven prior to remission, and in most cases, post-remission, rely on other strategies to mitigate myelosuppression. We report our center’s outcomes with this approach. Methods: All newly-diagnosed AML patients treated with commercially-obtained ven/aza outside of a clinical trial at our center from 2018 to 2024 were reviewed. Blood counts, doses/schedules of ven/aza, days between cycles, and transfusions were retrospectively collected. Kaplan-Meier estimates were used to evaluate overall survival (OS). Treatment cycles from each patient were analyzed individually. Results: 143 patients met inclusion criteria; median age was 70 years (IQR 65-76), 55.9% were male, and 62% had ELN adverse risk AML (80/143). ORR (CR+CRi+MLFS) was 85/143 (59.4%). The median number of cycles (C) completed was 2.9 (IQR 1-4, range 0-26), with 117 patients completing ≥1 cycle. Mean time between cycles 1-5 was 15 days (IQR 10-19 days). Death within 30 and 60 days was 12.6% (n=18) and 22.2% (n=32). The median OS was 331 days. Prior to response assessment (C1D~28), the majority (113/117, 96.6%) received 28 days of ven, and 113/117, 96.6% had no reductions in aza. Post-response, 17/82 (20.1%) had a ven reduction (in either duration or dose) and 33/82 (27.8%) had reductions in aza, during C2-4. 43 patients proceeded to allogeneic stem cell transplantation, the most common reason for ven/aza discontinuation. Percentage of patients requiring PRBC transfusions (C1: 77%, C2: 39%, C3: 14%, C4: 15%), and platelet transfusions (C1: 61%, C2: 24%, C3: 15%, C4: 12%) decreased throughout cycles. Severe neutropenia (absolute neutrophils < 500 c/uL) decreased in subsequent cycles, with peak incidence in C1 (88%) and lowest in C4 (42%). 37% of patients experienced neutropenic fever during C1. Conclusions: Reduced ven duration prior to bone marrow assessments on C1D28 were not typically performed in the phase 3 ven/aza study, yet has become a common strategy to reduce myelosuppression. Our institution explored utilizing breaks between cycles and reductions in aza. Using our mitigation strategies, 28 days of venetoclax can be administered before and after remission with myelosuppression and transfusion needs similar to published reports giving <28 days of ven. While it is not clear whether administration of 28 days of ven is the ideal duration, this analysis suggests it is possible to administer from a myelosuppression perspective.