Venetoclax combined with cacag regimen as a bridge to allogeneic hematopoietic stem cell transplantation in patients with previously untreated acute myeloid leukemia achieving CR1

Abstract Abstract Objective: To analyze the impact of venetoclax (VEN) combined with the CACAG induction regimen on 1-year relapse in previously untreated acute myeloid leukemia (AML) patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) after achieving first complete remission (CR1). Methods: This study consecutively enrolled 27 previously untreated AML patients who achieved CR1 with venetoclax plus CACAG induction followed by allo-HSCT between January 2022 and August 2024. The CACAG regimen included: venetoclax (100 mg on day 1, 200 mg on day 2, 400 mg on days 3–14; dose reduced to 100 mg/day when combined with azoles), chidamide (30 mg on days 1 and 4), azacitidine (75 mg/m² on days 1–7), cytarabine (75–100 mg/m² every 12 hours on days 1–5), aclacinomycin (20 mg on days 1, 3, and 5), and recombinant human granulocyte colony-stimulating factor (rhG-CSF, 300 μg/day until neutrophil recovery). A historical cohort of 27 AML patients who achieved CR1 with conventional 3+7 induction and underwent allo-HSCT between January 2019 and June 2021 was used for comparison. Outcomes including engraftment, acute/chronic GVHD, relapse, and survival were analyzed. Results: With a median follow-up of 433.5 days (range: 24–1982), the venetoclax-CACAG cohort showed reduced 1-year cumulative recurrence rate (CRR: 7.9% vs. 19.7%, p=0.21) and non-relapse mortality (NRM: 8.1% vs. 10.6%, p=0.95) compared to the historical cohort, though without statistical significance. The 1-year disease-free survival (DFS: 84.4% vs. 71.8%, p=0.43) and overall survival (OS: 92.1% vs. 90.0%, p=0.86) were numerically higher. Notably, the cumulative incidence of acute GVHD (aGVHD) by day +100 was significantly lower (29.6% vs. 59.3%, p=0.022), while the incidence of grade III/IV aGVHD (9.6% vs. 14.8%, p=0.17) showed a non-significant reduction. Conclusion: Compared to the historical cohort, venetoclax combined with CACAG reduced the incidence of aGVHD and demonstrated potential for improved relapse outcomes post-transplant.