Venetoclax Duration Does Not Significantly Impact OS in AML or MDS

Shorter venetoclax duration did not significantly impact overall survival (OS) in a real-world cohort of patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) treated at a community hospital.¹ The findings, presented at the 2025 American Society of Clinical Oncology (ASCO) annual meeting, suggest that shorter-duration venetoclax could be as effective as longer-duration venetoclax.

Previous research has indicated that shorter-duration venetoclax could be as effective as longer-duration venetoclax administration in newly diagnosed AML. In one study, a 14-day vs 21-day or 28-day venetoclax administration led to comparable efficacy in terms of complete response (CR) and CR with incomplete recovery (CRi) without compromising survival.² An ongoing randomized phase 2 study (NCT03013998) is comparing a 28-day vs 14-day schedule of venetoclax plus azacitidine in newly diagnosed AML.

Venetoclax duration did not have a significant impact on overall survival based on univariate analysis in patients with AML or MDS. | Image credit: Sviatlana-stock.adobe.com

“Hypomethylating agents (HMA) and venetoclax are routinely used in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS),” the authors of the study presented at ASCO wrote.¹ “Limited data exist on varied venetoclax duration and have not revealed significant outcome differences.” In the new study, they examined real-world prescribing patterns and early outcomes of venetoclax in patients with AML and MDS.

The study included 53 patients who received frontline HMA and venetoclax between January 2020 and December 2023. The patient population was 62% male, and the median age was 69 years (range, 63-73). Patients were grouped by the duration of venetoclax treatment, which lasted 7, 14, 21, or 28 days. The majority of patients (81%) received decitabine, had adverse European LeukemiaNet (ELN) risk factors (83%), and had de novo AML (66%). Nineteen patients underwent allogeneic stem cell transplants.

Response at first post-treatment biopsy, OS, 1-year survival, grade 3 or higher neutropenia/thrombocytopenia, time to count recovery, and incidence of tumor lysis syndrome (TLS) and bacteremia were all examined. The median follow-up was 10.7 months (range, 3.3-43) overall but 21.6 months (range, 10.7-43) for surviving patients. There was only 1 patient in the venetoclax 21 group, so this group was excluded from further analysis of outcomes, the authors noted.

One-year OS was significantly improved in the venetoclax 28 group (66.4%) vs the venetoclax 7 group (33.3%; P = .014). However, the venetoclax cohorts did not show significant differences in complete response (CR) or CRi. Rates of minimal residual disease (MRD) were also similar across the cohorts, with 48% of patients achieving MRD negativity.

Regarding OS, venetoclax duration did not have a significant impact based on univariate analysis. The same was found for ELN risk status and age.

Almost all patients experienced grade 3 or higher neutropenia (96.4%) and thrombocytopenia (82.8%) with no statistically significant between-group differences. The time to count recovery was similar between groups. Rates of TLS and bacteremia occurrence were low (9.6% and 3.8%, respectively).

“In this community hospital cohort, venetoclax 7 patients had significantly worse 1-year OS vs venetoclax 28; there was no difference in OS,” the authors wrote. “Our findings, consistent with other retrospective studies, imply shorter venetoclax durations may be as effective but with minimal difference in hematologic toxicities.”

The authors noted that selection bias in prescribing patterns is likely in their study and other retrospective studies and that more data are required to confirm whether shorter durations of venetoclax provide equivalent benefits.

References

1. Williams M, Biswas A, Johnson RR, et al. Venetoclax duration outcomes analysis in MDS/AML within a community hospital. J Clin Oncol. 2025;43(suppl 16). doi:10.1200/JCO.2025.43.16_suppl.e18511

2. Karrar O, Abdelmagid M, Rana M, et al. Venetoclax duration (14 vs. 21 vs. 28 days) in combination with hypomethylating agent in newly diagnosed acute myeloid leukemia: Comparative analysis of response, toxicity, and survival. Am J Hematol. 2024;99(2):E63-E66. doi:10.1002/ajh.27180