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

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.