Venetoclax and Hypomethylating Agents in Octo- and Nonagenarians with Acute Myeloid Leukemia

Venetoclax (VEN) plus HMA regimen is the standard of care for older adults with AML, however it is associated with significant myelosuppression and complications, potentially limiting its use in the very old. We performed a multi-center retrospective analysis of VEN-HMA treatment in octo- and nonagenarians to further understand the tolerability, feasibility, dosing considerations, and clinical efficacy in this unique group. AML patients 80 years or older 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. One hundred fifty-four patients were included, with a median age of 82 years (range 80-92), who received treatment with VEN-HMA (83% with AZA, 17% with DEC). Most patients (53%) had ELN 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 CRc rate for newly diagnosed AML patients without prior MDS was 73% (48/66). Median OS was 8.1 months and in patients who achieved a response (CRc), median OS was 13.2 months. Landmark analysis from time CRc was first achieved showed patients receiving VEN for 14 days or less had improved OS, median 24.0 months. The 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.