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.