Venetoclax combined with cladribine, idarubicin, cytarabine ( CLIA ‐ VEN ) results in higher remission rates over conventional 7 + 3 chemotherapy without increased toxicity in newly diagnosed acute myeloid leukaemia

Summary Induction chemotherapy in fit de novo acute myeloid leukaemia (AML) patients has historically combined an anthracycline with standard‐dose cytarabine (‘7 + 3’) despite complete response (CR) rates of 50%–70%. In May 2023, our institution adopted the utilization of cladribine, cytarabine, idarubicin and venetoclax (CLIA‐VEN) for intensive remission–induction therapy. In this retrospective study, outcomes of newly diagnosed adult AML patients who were consecutively treated with CLIA‐VEN ( n = 20; 2023–2025) were compared to a historical cohort that received 7 + 3 ( n = 42; 2016–2023). The median interquartile range [IQR] age was 54 [42–63] years, 54% were male and 58% had European LeukemiaNet (ELN) 2022 adverse‐risk disease. CLIA‐VEN was associated with a higher cumulative incidence of composite CR (CCR) (90% vs. 54.8%; p = 0.002) and minimal residual disease (MRD)‐negative CCR (93.8% vs. 40.9%; p < 0.001) at 28 days. Any grade ≥ 2 end‐organ toxicity (45% vs. 59.5%; p = 0.28) and early mortality (0% vs. 16.7%; p = 0.09) were not increased with CLIA‐VEN. Utilizing propensity score guided inverse probability treatment weighting to balance baseline demographics, receipt of CLIA‐VEN was associated with improved overall survival ( p = 0.002). Acknowledging the limitations of a retrospective single‐centre study, our data suggest that CLIA‐VEN has higher efficacy without increasing toxicity and the potential to prolong survival compared to the current standard of care in de novo AML patients.