Evaluation of venetoclax and hypomethylating agent combination therapy in acute myeloid leukemia: a real-life, single-center experience

Aim The use of venetoclax in combination with hypomethylating agents (HMAs) has become a standard treatment approach for both newly diagnosed and relapsed/refractory (R/R) AML patients who are ineligible for intensive chemotherapy. We aimed to share the real-life data of this combination therapy. Method This retrospective study included 38 patients with newly diagnosed or R/R AML who received at least one cycle of venetoclax-HMA combination therapy between July 2018 and August 2025. Response status, survival rates, and the incidence of hematological adverse events were analyzed. Results Twelve patients (31.6%) were treatment-naive, while the remaining 26 (68.4%) were R/R AML. The median age of all patients was 67, and 57.9% were male. 23.7% of the patients were in the poor-risk group. The overall response rate (ORR) was 73.7% in the entire cohort, and 83.3% and 69.2% in the first-line and R/R groups, respectively. No statistically significant difference in ORR was observed between the newly diagnosed and R/R groups ( p = 0.453); however, given the small sample sizes — particularly in the newly diagnosed arm ( n = 12) — this study was insufficiently powered to detect or exclude a clinically meaningful difference between groups. The restricted mean progression-free survival (RMST-PFS) was 18.35 months (95% CI 15.16–21.22), and the restricted mean overall survival (RMST-OS) was 21.12 months (95% CI 19.03–22.86). As adverse events, grade 3 or higher neutropenia was 39.5% and thrombocytopenia was 31.6%. Conclusion In this single-center real-world experience, venetoclax-HMA combination therapy demonstrated response rates and a toxicity profile consistent with those reported in larger studies, supporting its feasibility in routine clinical practice for AML patients ineligible for intensive chemotherapy.