Reduced venetoclax exposure to 7 days vs standard exposure with hypomethylating agents in newly diagnosed AML patients

Abstract

Hypomethylating agent (HMA) plus venetoclax (VEN) regimens are standard of care in patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. While the VEN label recommends continuous 28-day cycles, shortened VEN durations may induce similar response rates and improve tolerability. It is unknown how a VEN exposure reduced to 7 days during cycles compares to standard HMA + VEN. We retrospectively compared newly diagnosed AML patients treated with azacitidine (AZA) x 7 days plus VEN x 7 days ("7 + 7" regimen) from the first cycle (n = 82) vs patients treated with standard dose HMA + VEN (std-HMA/VEN) (n = 166). Composite complete remission rate was similar between cohorts (72% vs 72%; p = 0.95) and a median number of cycles to best response was 2 with "7 + 7" vs 1 with std-HMA/VEN (p = 0.03). Concerning toxicity, platelet transfusion rates during cycle 1 as well as early mortality at 8-weeks (6% vs 16%; p = 0.03) were lower in "7 + 7" cohort. Finally, the median OS was 11.2 months (2-year 28%) with "7 + 7" vs 10.3 months (2-year 34%) with "std-HMA/VEN" (p = 0.75). In summary, acknowledging limitations of a retrospective comparison, a shortened course of VEN used for 7 days every 28 days resulted in similar response rates and survival when compared to standard VEN exposure.