Abstract
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.