Hypomethylating agents with venetoclax for newly diagnosed acute myeloid leukemia in patients 65 and older in The Netherlands - A nationwide study of drug usage and treatment outcomes.

INTRODUCTION: For patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy the combination of a hypomethylating agent (HMA) with venetoclax (VEN) has become the standard of care. DESIGN: We conducted a retrospective real-world study across 15 hospitals involving patients aged ≥ 65 who were newly diagnosed with AML during the 18 months following the introduction of VEN in The Netherlands. RESULTS: A total of 209 patients treated with HMA + VEN as first-line therapy (median age 73.9 years, 12% ECOG ≥ 2, 26% decitabine), were included and followed for a median of 25.9 months. Composite complete remission was achieved in 69% of patients while 3-month-mortality was 15%. The median overall survival was 19.1 months (22.1, 10.9, and 6.8 months for the ELN2024 high-, intermediate- and lower-benefit groups), and 14.7 months in patients not transplanted. Transplantation, accomplished in 37 patients (18%), was associated with improved survival (HR for death 0.24; p < 0.001). Antifungal agents were used in 72% of first cycles and were associated with lower mortality (multivariable HR 0.605; p = 0.010), also leading to VEN dose reductions. A total of 101 patients (48%) received follow-up therapy (cycles 4 and onwards, median 11 cycles), 47 of which were alive at data-cutoff. Follow-up therapy was commonly initiated with 14 (55%) or 7 days (15%) of VEN. Overall, 38 patients (18%) switched to HMA monotherapy. CONCLUSIONS: Our findings showcase how encouraging survival outcomes can be achieved in the real world while simultaneously realizing considerable VEN savings through cycle individualization and strategic usage of drug-drug interactions.