Real-World Effectiveness of First-Line Azacitidine or Decitabine with or without Venetoclax in AML Patients Unfit for Intensive Therapy

Standard frontline 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 are sparse and have shown conflicting results. Thus, we performed a multicenter retrospective analysis of outcomes with HMA-VEN compared to HMA alone in patients with newly diagnosed AML unfit for intensive treatment. A total of 213 patients were identified from 3 German tertiary care centers. Of those, 125 were treated with HMA-VEN and 88 with HMA alone. Median overall survival (OS) in the HMA-VEN cohort was 7.9 months (95% confidence interval [CI], 5.1–14.7) compared to 4.9 months (3.1–7.1) with HMA alone. After 1 year, 42% (95% CI, 33–54) and 19% (12–30) of patients were alive, respectively. The hazard ratio (HR) for death was 0.64 (95% CI, 0.46–0.88; p = 0.006). After adjusting for age, NCCN cytogenetic risk, NPM1, RUNX1, and TP53 status, ECOG performance status, baseline leukocytes, and type of HMA, treatment with HMA-VEN remained significantly associated with a prolonged survival (HR, 0.48; 95% CI, 0.29–0.77). Accordingly, time to next treatment (TTNT) was longer with HMA-VEN with a HR of 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). These data align with findings from the pivotal VIALE-A trial and support the use of HMA-VEN in patients unfit for intensive therapy.