Venetoclax combined with three-day multi-frequency decitabine, vincristine and dexamethasone (VDVD) as induction treatment for patients with de novo acute leukaemias of ambiguous lineage

Abstract Background Acute leukaemias of ambiguous lineage (ALAL) is a rare and highly heterogeneous acute leukemia. Adult patients with ALAL induced by conventional chemotherapy have multiple complications and the therapeutic effect is unsatisfactory. However, prior research has indicated that incorporating Venetoclax (VEN) can enhance efficacy for these patients. Our preliminary findings suggest that a combination of VEN with three-day multi-frequency Decitabine (DEC) demonstrates both notable safety and significant effectiveness in newly diagnosed elderly patients with acute myeloid leukemia. To explore the more appropriate treatment regimens, we designed VDVD as induction therapy for patients with de novo ALAL. Method The induction regimen VDVD consisted of a 11-day oral administration of VEN (100mg Day 1; 200mg Day 2;400mg Days 3-11), in combination with three-day DEC (20 mg/m2/q8h, Days 4–6 and infusion time ≥2 h), Vincristine (2mg Days 1、8) and Dexamethasone (10 mg/m2/d, Days 1–4 and d8-11). If the BCR/ABL fusion gene was positive at diagnosis, a daily dose of 100mg dasatinib was administered from the eighth day onwards. After achieving CR or CRi, allogeneic hematopoietic stem cell(allo-HSCT) was recommended for the patients. Patients who cannot proceed allo-HSCT received consolidation therapy. The primary purpose was evaluated the efficacy and safety of VDVD as induction regimen in patients with de novo ALAL. Secondary purpose was overall survival (OS), event-free survival (EFS), disease-free survival (DFS). Results Between September 2022 and March 2025, 18 de novo ALAL patients were enrolled and treated with VDVD as induction therapy. The median age was 58.5 years (range, 15-71), and 10 (55.56%) patients were male. Among the 18 patients, 9 were diagnosed with MPAL-T/M, 2 were diagnosed with MPAL-B/M, 2 were diagnosed MPAL with BCR::ABL1 fusion, 3 were diagnosed with ALAL-NOS, and 2 were diagnosed with AUL. After one cycle of induction treatment, the ORR (overall response rate, CR + MLFS) was 88.89% (16/18), with complete remission rate 83.33% (15/18). Grade 3 or worse adverse effects included neutropenia, thrombocytopenia, febrile neutropenia. None of patients died during the induction therapy. Until June 30, 2025 with a median follow-up time of 8 months (range: 2-33), 2 (11.1%) patients underwent allo-HSCT, the median OS time is 8 months (range: 2-33), and the median EFS and RFS time both are 7 months (range: 1-22). ConclusionVDVD is a highly effective and safe induction therapy for de novo acute leukaemias of ambiguous lineage patients.