Hypomethylating agents plus venetoclax in younger acute myeloid leukemia: Meta-analysis of a shifting treatment paradigm.

[BACKGROUND] In younger, fit patients with acute myeloid leukemia (AML), intensive chemotherapy (IC) followed by consolidation or allogeneic hematopoietic stem cell transplantation (HSCT) is the standard approach. The authors performed a systematic review and meta-analysis to evaluate younger patients with AML treated with hypomethylating agents (HMA) plus venetoclax.

[METHODS] This systematic review and meta-analysis was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. MEDLINE and the Cochrane Library were systematically searched through February 2026. Studies included AML patients with a median age <70 years treated with HMA/venetoclax. Primary outcomes were complete remission (CR/CRi) rate, measurable residual disease (MRD) negativity, 1-year overall-survival (OS), 1-year event-free survival (EFS), and rates of HSCT.

[RESULTS] Eight studies (two randomized controlled trials, two phase 2 trials, and four real-world studies), comprising 429 patients with a mean age of 54 years, were included. The pooled CR/CRi rate was 66% (95% confidence interval [CI], 48%-85%), with an MRD-negative rate of 69% (95% CI, 49%-90%). The pooled 1-year OS was 75% (95% CI, 63%-86%), exceeding Surveillance, Epidemiology, and End Results database cohorts (62%). The 1-year EFS was 59% (95% CI, 53%-65%), with low between-study heterogeneity. Overall, 66% of patients successfully proceeded to HSCT. Meta-regression analyses suggested a trend toward improved EFS and OS in studies using decitabine than azacitidine.

[CONCLUSIONS] In younger patients with AML, HMA plus venetoclax yielded high response rates, MRD negativity, and a substantial proportion of patients proceeding to HSCT. These findings support HMA/venetoclax as an effective induction strategy in selected younger patients and provide a rationale for prospective randomized trials comparing this approach with IC-based regimens.