TOPLINE:

In younger patients with acute myeloid leukemia (AML), hypomethylating agents (HMA) plus venetoclax achieved a pooled complete remission rate (CR/CRi) of 66% and measurable residual disease (MRD) negativity of 69%, with more than two thirds of patients successfully bridging to hematopoietic stem-cell transplantation (HSCT). The pooled 1-year overall survival (OS) of 75% exceeded historical population-based data, suggesting this less-intensive approach may offer an effective alternative to intensive chemotherapy in selected younger patients.

METHODOLOGY:

• The favorable efficacy-to-toxicity profile of HMA plus venetoclax has prompted growing interest in its use beyond the elderly and unfit population, including younger patients, as a potential alternative to conventional intensive chemotherapy. Early-phase trials and real-world studies suggest this approach may induce high-quality remissions while preserving performance status and facilitating transition to HSCT.
• Researchers conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, searching MEDLINE and the Cochrane Library through February 2026 for studies of patients with AML having a median age < 70 years treated with HMA plus venetoclax.
• A total of 429 patients from eight studies (two randomized controlled trials, two phase 2 trials, and four real-world studies) with a mean age of 54 years were included, including patients from China (166 patients), the US (136 patients), and Europe (127 patients).
• Primary outcomes assessed were CR/CRi rate, MRD negativity, 1-year OS, 1-year event-free survival (EFS), and rates of HSCT, with pooled estimates calculated using random-effects models.
• Three studies used decitabine as the HMA backbone, three used azacitidine, and two included mixed cohorts treated with either azacitidine or decitabine in combination with venetoclax.
• Meta-regression analyses explored the impact of patient age and HMA backbone (azacitidine vs decitabine) on outcomes, with statistical heterogeneity assessed using Cochran Q test and quantified by the I² statistic.

TAKEAWAY:

• The pooled CR/CRi rate was 66% (95% CI, 48%-85%), with substantial heterogeneity (P < .001), and the pooled MRD-negative rate was 69% (95% CI, 49%-90%), with considerable heterogeneity.
• The pooled 1-year EFS was 59%, with minimal between-study heterogeneity and the pooled 1-year OS was 75%, with low heterogeneity.
• Overall, 66% of patients (95% CI, 48%-84%) successfully proceeded to HSCT, with rates ranging from 33% to 99% across studies, reflecting variability in study design and transplant-focused intent.
• Meta-regression analyses suggested a trend toward improved EFS and OS in studies employing decitabine rather than azacitidine as the HMA backbone, and studies enrolling patients with a median age < 45 years demonstrated superior EFS than patients with a median age > 47 years.

IN PRACTICE:

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 [intensive chemotherapy]-based regimens, wrote the authors of the study.

SOURCE:

The study was led by Salvatore Perrone, MD, S. M. Goretti Hospital, Polo Universitario Pontino, Latina, Italy. It was published online in Cancer.

LIMITATIONS:

The included evidence derives from heterogeneous sources, encompassing randomized trials, phase 2 studies, and real-world analyses conducted across different geographic regions, with variability in patient selection, treatment protocols, and outcome definitions. Detailed molecular and genetic data were not consistently available, precluding patient-level analyses that could refine risk stratification and treatment selection. The decision to administer HMA plus venetoclax in younger patients was not uniformly driven by chronological age alone but reflected heterogeneous clinical contexts, including comorbidity burden, physician discretion, and adverse-risk disease biology, which limits definitive conclusions regarding optimal patient selection. The use of predefined age thresholds as pragmatic inclusion criteria is an inherent methodological constraint because biological fitness is a more clinically meaningful determinant of treatment intensity than chronological age. Considerable heterogeneity was observed for response and MRD outcomes, likely reflecting variability in response-assessment methods, MRD-detection techniques, timing of evaluations, and treatment schedules across studies.

DISCLOSURES:

No disclosures or conflict of interest statements were provided in the study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.