Study Reveals Venetoclax Duration's Limited Impact on Survival in AML and MDS

A recent study presented at the 2025 American Society of Clinical Oncology (ASCO) annual meeting indicates that shorter durations of venetoclax treatment in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) yield comparable overall survival (OS) outcomes to longer durations. This challenges the prevailing treatment norms and prompts a reevaluation of treatment protocols in these patient populations.

The research, which examined a cohort of 53 patients treated at a community hospital from January 2020 to December 2023, was conducted by Dr. Mark Williams, Dr. Arjun Biswas, Dr. Robert Johnson, and colleagues. The study's findings suggest that venetoclax, when administered for shorter durations, does not significantly compromise survival outcomes. According to Dr. Williams, “Our findings indicate that shorter venetoclax durations may be as effective as longer durations, with minimal differences in hematologic toxicities.”

Historically, venetoclax has been used in combination with hypomethylating agents (HMAs) in AML and MDS treatment. Previous studies indicated that shorter treatment durations could maintain efficacy levels comparable to longer administrations, yet there remained limited real-world data to confirm these findings.

In the presented study, patients were divided based on the duration of venetoclax treatment: 7, 14, 21, or 28 days. The majority of the cohort, 81%, received decitabine, and 83% exhibited high-risk factors according to European LeukemiaNet (ELN) guidelines. The median age of participants was 69 years, with a predominance of male patients (62%). Although one-year OS was significantly better for the 28-day cohort (66.4%) compared to the 7-day cohort (33.3%), the overall survival rates between the various treatment durations were not statistically different.

The study also highlighted significant toxicities; nearly all patients experienced grade 3 or higher neutropenia (96.4%) and thrombocytopenia (82.8%), yet these did not vary significantly across the groups. Importantly, the study reported low rates of tumor lysis syndrome (TLS) and bacteremia, at 9.6% and 3.8%, respectively.

Dr. Emily Tran, Assistant Professor of Oncology at Johns Hopkins University, expressed caution regarding the implications of the study. “While the results are promising for shorter venetoclax treatments, further randomized controlled trials are essential to ascertain the long-term outcomes and safety profiles associated with these treatment durations,” she stated.

The ongoing phase 2 randomized trial (NCT03013998) comparing 14-day versus 28-day venetoclax administration in newly diagnosed AML patients could provide further insights into optimal treatment strategies.

In summary, the study's findings contribute to a growing body of evidence suggesting that shorter venetoclax durations may offer equivalent clinical benefits for patients with AML and MDS, highlighting the need for future research to validate these results and refine treatment protocols accordingly. As the medical community continues to explore optimal treatment durations, these findings could reshape therapeutic approaches in hematologic malignancies, aligning them more closely with patient needs and safety profiles.

**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