Venetoclax combined with hypomethylating agents for the treatment of newly diagnosed with mixed-phenotype acute leukemia and a literature review

Ruihua Mi¹Shuli Guo²Weidong Yang³Lin Wang¹Yixuan Ma¹Lin Chen¹Dongbei Li^1,4Xudong Wei^1*

• ¹Henan Cancer Hospital/Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
• ²Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, China
• ³Anyang District Hospital, Anyang, China
• ⁴Henan academy of Innovations in Medical Science, Zhengzhou, China

Objective To investigate the efficacy and safety of venetoclax (Ven) in combination with hypomethylating agents (HMAs) for the treatment of mixed-phenotype acute leukemia (MPAL). Methods From July 2023 to April 2025, 4 newly diagnosed MPAL patients treated with Ven combined with HMAs at the Affiliated Cancer Hospital of Zhengzhou University, Luoyang Central Hospital and Anyang Regional Hospital were retrospectively analyzed to determine the efficacy and safety of this treatment. The relevant published studies were reviewed. Results This study included four patients (2 males, 2 females) with a median age of 47 years (range: 40–80 years). Three patients were classified as having B/myeloid MPAL, and one was classified as having T/myeloid MPAL. All patients achieved complete remission (CR) after one cycle of venetoclax combined with HMAs. Notably, Patient 3, who tested positive for the BCR::ABL1 fusion gene, received additional tyrosine kinase inhibitor (TKI) therapy. The median duration of myelosuppression during induction therapy was 26 days (range: 7–36). Patients 1 and 4 developed infections during induction, which were controlled with aggressive antimicrobial treatment and supportive care. In contrast, Patients 2 and 3 tolerated the regimen well without significant adverse events. Conclusion The treatment of MPAL with Ven combined with HMAs achieved a high remission rate and can be used as an alternative treatment for MPAL.