Short-Duration Venetoclax Plus Decitabine Shows Comparable AML Outcomes
Key Clinical Summary
- A reduced 10-day venetoclax schedule with decitabine achieved a 53% composite complete remission rate in newly diagnosed acute myeloid leukemia (AML).
- Outcomes were consistent across high-risk groups, including TP53-mutated and adverse-risk disease.
- Infection rates (35% overall; 26% ≥grade 3) suggest a potentially improved safety profile vs longer venetoclax regimens.
A retrospective real-world study from the University of Alabama at Birmingham evaluated a shortened venetoclax schedule combined with decitabine in newly diagnosed AML. The regimen was assessed in older and unfit patients, a population typically treated with hypomethylating agents plus 28 days of venetoclax, where toxicity often necessitates dose modifications.
Study Findings
The analysis included 72 consecutive patients treated between March 2024 and March 2025 with decitabine 20 mg/m² intravenously for 5 days and venetoclax 400 mg orally for 10 days per cycle (DEC5/VEN10). The median age was 72 years, and 85% of patients had European LeukemiaNet (ELN) 2022 adverse-risk disease. High-risk molecular features were common, including TP53 mutations in 37.5% and complex karyotype in 33.3%.
Among evaluable patients, the composite complete remission (CRc) rate was 53%, and the overall response rate (ORR) was 63%. When excluding patients whose venetoclax duration was later extended to 28 days, CRc and ORR remained similar at 52% and 61%, respectively. Minimal residual disease (MRD)-negative CRc was achieved in 25% of patients, with a median of 2 cycles required to reach remission.
Subgroup analyses showed CRc/ORR rates of 55%/73% in patients with IDH1/2 mutations and 46%/50% in those with TP53 mutations. Outcomes were consistent across ELN 2024 risk groups, including a 46% CRc rate in adverse-risk disease.
At a median follow-up of 9 months, median overall survival was 8.44 months, and median event-free survival was 6.18 months. Infection occurred in 35% of patients, with grade 3 or higher infections reported in 26%.
Clinical Implications
These findings are relevant for oncology clinicians and payers designing AML clinical pathways, particularly for older or frail patients. The standard 28-day venetoclax schedule is associated with significant cytopenias and infection risk, often requiring real-world dose adjustments.
The DEC5/VEN10 regimen appears to maintain efficacy while potentially reducing toxicity, supporting shorter venetoclax exposure as a viable strategy. Comparable remission rates across adverse-risk and TP53-mutated populations suggest that reduced duration does not compromise outcomes in biologically high-risk AML.
For pathway decision-makers, this approach may help optimize treatment tolerability, reduce hospitalization from infections, and improve adherence. However, variability in venetoclax duration across cycles and the retrospective design highlight the need for prospective validation before widespread adoption.
Investigators noted that the regimen “yielded comparable efficacy to published clinical trials and real-world data, even in adverse-risk subgroups.” They further emphasized an “apparent improved safety profile,” particularly a lower rate of infections, supporting its feasibility in older and frail patients.
Conclusion
A 10-day venetoclax schedule with decitabine demonstrated encouraging efficacy and safety in newly diagnosed AML. Ongoing follow-up will clarify durability and survival outcomes, informing whether shorter venetoclax regimens can be integrated into standard AML treatment pathways.
Reference
McCormick B, Jamy O, Espinoza-Gutarra M, et al. Real-world outcomes of shortened venetoclax course plus decitabine in newly diagnosed acute myeloid leukemia. Presented at: ASH 2025; December 6-9; Orlando, FL.
