The impact of venetoclax treatment duration on efficacy and hematologic toxicity in acute myeloid leukemia: a systematic review and meta-analysis

Venetoclax (VEN) combined with hypomethylating agents (HMA) is a standard treatment for unfit acute myeloid leukemia (AML) patients, but the conventional 28-day cycle often leads to prolonged cytopenias and infection risks. Recent studies suggest shorter VEN regimens may improve safety without compromising efficacy, but this remains controversial. To this end, we performed a systematic review and meta-analysis to compare the impact of VEN duration in patients receiving VEN-HMA. A comprehensive literature search was conducted in PubMed and Embase up to May 28, 2025. The Cochran Q test and I-squared statistics were used to identify the heterogeneity among the included studies. The network meta-analysis was performed by employing The mtc.model and mtc.run functions of the gemtc R package. We performed all statistical analyses using R 4.0.3. Six studies with 728 patients were included. Meta-analysis showed no significant difference in remission rates between shorter (≤ 14 days) and longer (> 14 days) treatments (RR = 1.07, 95% CI: 0.95–1.20). Network meta-analysis of 14-day (VEN14), 21-day (VEN21), and 28-day (VEN28) regimens found no statistically significant differences in remission rates or overall survival (OS), with VEN14 ranking first for both remission efficacy and survival benefit. Although grade 3/4 granulocytopenia was similar across groups, VEN21 correlated with significantly lower febrile neutropenia versus VEN28 (RR = 0.56, 95% CI: 0.29–0.98). Shorter VEN courses (14–21 days) appear to maintain comparable efficacy to the standard 28-day course, with VEN21 potentially offering a better safety profile regarding febrile neutropenia, supporting the individualization of treatment duration to improve tolerability in unfit AML patients.