Safety and efficacy of venetoclax-azacitidine combined with low-dose idarubicin and cytarabine regimens for the treatment of newly diagnosed acute myeloid leukemia patients compared to the standard chemotherapy: a propensity score-matched real- world single-center experience

Long-term survival of patients with acute myeloid leukemia (AML) remains poor. For newly diagnosed AML patients, the compete remission (CR) rate reaches 60 ~ 80% with standard induction chemotherapy. Combined multi-target therapy can improve the response rate, overcome chemoresistance, and improve the survival rate of patients. Improved induction regimens are needed. No previous studies had assessed the efficacy and safety of venetoclax-azacitidine combined with low-dose idarubicin and cytarabine (VAIA) for newly diagnosed (ND) AML patients. Using propensity score matching (PSM) we analyzed the prognosis of patients with ND-AML treated with VAIA and idarubicin-cytarabine (IA). The primary outcomes evaluated in this study were CR rate and measurable residual disease (MRD)-negative CR rate. The secondary outcomes included overall survival (OS), leukemia-free survival (LFS) and safety. Between January 2023 and June 2024, 26 AML patients were treated with VAIA. PSM paired 52 AML patients treated with IA. No significant clinical or molecular differences were observed between cohorts. The CR and MRD-negative CRc rate of the VAIA cohort were significantly higher than that of the IA cohort (84.3% vs 61.5%, P = 0.037 for CR, and 80.8% vs 53.8%, P = 0.026 for MRD-negative CRc). The application of VAIA regimens contributed to survival prolongation than standard induction chemotherapy, with a significantly higher OS and LFS rates (1-year OS: 76.9% vs. 57.7%, P = 0.031; 1-year LFS: 64.2% vs. 46.2%, P = 0.042). Subgroup analysis showed that the prognosis of VAIA treatment was significantly benefit than IA in the high-risk group (OS: 69.2% vs 32%, P = 0.045; LFS: 61.5% vs 20%, P = 0.046). Regardless of which induction treatment received, MRD-negative patients had significantly longer OS and LFS than patients who were MRD positive (1-year OS: 65.3% vs. 41.4%, P = 0.042; 1-year LFS: 56.4% vs. 37.9%, P = 0.009). The therapeutic effects of VAIA are superior to IA in patients with IDH2, ASXL1 and NRAS mutations. VAIA was associated with an expected and manageable toxicity profile consisting mainly of infectious and myelosuppressive adverse events; the 30-day and 60-day mortality rates were low.