Venetoclax and hypomethylating agents in octogenarians and nonagenarians with acute myeloid leukemia

Abstract

AbstractVenetoclax (VEN) plus a hypomethylating agent (HMA) regimen is the standard of care for older adults with acute myeloid leukemia (AML), however it is associated with significant myelosuppression and complications, potentially limiting its use in those who are very old. We performed a multicenter retrospective analysis of VEN-HMA treatment in octogenarians and nonagenarians to further understand the tolerability, feasibility, dosing considerations, and clinical efficacy in this unique group. Patients with AML aged ≥80 years who received VEN-HMA between March 2015 and April 2022 were reviewed. VEN-HMA dosing was determined by treating physician, accounting for CYP3A4 drug interaction dose adjustments. In total, 154 patients were included, with a median age of 82 years (range, 80-92), who received treatment with VEN-HMA (83% with azacitidine, and 17% with decitabine). Most patients (53%) had European LeukemiaNet 2017 adverse risk AML, 33% had intermediate, 8% had favorable, and 6% were unknown. With a median follow-up of 7.7 months, 36 patients (23%) remained in remission, with 31 (20%) still on VEN-HMA. The 30-day and 60-day mortality rates were 8.5% and 17%, respectively. The composite complete remission (CRc) rate for patients with newly diagnosed AML without prior myelodysplastic syndrome was 73% (48 of 66). Median overall survival (OS) was 8.1 months, and in patients who achieved a response (CRc), median OS was 13.2 months. Landmark analysis from the time CRc was first achieved showed that patients receiving VEN for ≤14 days had improved OS; median, 24.0 months. Patients who are very old can be treated safely with combination VEN-HMA with expectations of dose reductions and cycle extensions to ensure tolerability over the long term.