Real‐world effectiveness of first‐line azacitidine or decitabine with or without venetoclax in acute myeloid leukemia patients unfit for intensive therapy

Abstract Background First‐line treatment in patients with acute myeloid leukemia (AML) unfit for intensive therapy is the combination of a hypomethylating agent (HMA) with venetoclax (VEN). However, retrospective data confirming the benefits of this regimen outside of clinical trials have shown conflicting results. Methods We performed a multicenter retrospective analysis of outcomes with first‐line HMA–VEN versus HMA in AML patients unfit for intensive chemotherapy. Results A total of 213 patients were included from three German hospitals (125 HMA–VEN, 88 HMA). Median overall survival in the HMA–VEN cohort was 7.9 months (95% confidence interval CI, 5.1–14.7) versus 4.9 months (3.1–7.1) with HMA. After 1 year, 42% (95% CI, 33–54) and 19% (12–30) of patients were alive, respectively (hazard ratio HR for death, 0.64; 95% CI, 0.46–0.88). After adjusting for clinical and molecular baseline characteristics, treatment with HMA–VEN remained significantly associated with both prolonged survival (HR, 0.48; 95% CI, 0.29–0.77) and time to next treatment (HR, 0.63; 95% CI, 0.47–0.85). Patients who achieved recovery of peripheral blood counts had a favorable prognosis (HR for death, 0.52; 95% CI, 0.33–0.84). Discussion These data align with findings from the pivotal VIALE‐A trial and support the use of HMA–VEN in patients unfit for intensive therapy.