7-day venetoclax combined with intensive chemotherapy as induction treatment in high-risk newly diagnosed Acute Myeloid Leukemia

Abstract INTRODUCTION Acute myeloid leukemia (AML) in the high-risk group accounts for about 40-50% of adult acute myeloid leukemia, with a low response rate and poor long-term survival to conventional chemotherapy. In recent years, Venetoclax (VEN) combined with intensive chemotherapy(IC) has significantly improved the complete remission (CR) rate and MRD(-) rate in newly diagnosed AML patients, but the efficacy in patients with high-risk prognosis is still unclear, in order to further explore the efficacy of VEN combined with IC for high-risk AML patients.Herein, we reported the data of 80 patients with newly diagnosed high-risk AML who received 7-day VEN combined with IC (DA, HAA, or HAD) as induction treatment. To further validate the efficacy and safety of VEN combined with IC for AML in high-risk groups. METHODS The patients included in this study were derived from two clinical trials (VEN+DA: ChiCTR2200061524; VEN+HAA: ChiNCT05893472) and one retrospective study (VEN+HAD). All induction regimens include a 7-day oral administration of VEN, in combination with either DA (DNR 60 mg/m²/day d2-3, and Ara-c 100 mg/m²/q12h d2-7), HAA (HHT at 2.5mg/m2/day d3-7, Ara-c 100 mg/m²/day d3-7, and Acla 20mg/day d3-7), or HAD regimen (HHT at 2mg/m2/day d2-6, DNR 45 mg/m²/day d 4-5, and 100 mg/m²/day d2-6). After achieving CR, allogeneic hematopoietic stem-cell transplantation (allo-HSCT) were recommended according to ELN guidelines (2022). Patients who could not proceed allo-HSCT received consolidation and maintenance therapy. The primary objective of this study was to assess the effectiveness and safety of a 7-day VEN-based induction therapy in patients with high-risk AML. The secondary objectives were to evaluate overall survival (OS) and event-free survival (EFS). RESULTS Between January 2023 and June 2024, a total of 80 de novo high-risk patients were enrolled and treated with VEN combined with IC as induction therapy. Among them, 38 patients underwent treatment with VEN+DA, 32 patients received VEN+HAA, and 10 patients were treated with VEN+HAD. The cCR(CR+CRi) rate in the entire cohort was 85.0%(CR 67/80，CRi 1/80), and the MRD(-) rate was 80.0% by flow cytometry. Comparing treatment subgroups, the cCR rates were 86.8% (CR 32/38，CRi 1/38) for VEN+DA, 81.3% (CR 26/32，CRi 0/32) for VEN+HAA, and 90.0%(CR 9/10，CRi 0/10) for VEN+HAD (p=0.722) and MRD negtive rates were 78.9% (30/38), 81.3% (26/32), and 80.0% (8/10), respectively (p=0.972). The most frequent adverse effects were neutropenia (100%), thrombocytopenia (100%) and pneumonia (63.8%). The median recovery time for neutrophils and platelets were 14(range:7-52) and 13(range:4-63) days, respectively. Until April,30, 2025, with a median follow-up of 19(1-38) months, 40.0% of patients underwent allo-HSCT (28.9% in VEN+DA, 40.6% in VEN+HAA, and 80.0% in VEN+HAD, p=0.014). The median OS and EFS were not reached. The estimated 24-month OS and EFS were 60.6% (95% CI: 48.4-72.8%) and 57.8% (95% CI: 46.4-69.2%) in the entire cohort, 55.8% (95% CI: 38.2-73.4%) and 55.2% (95% CI: 38.3-72.1%) in the VEN+DA group, 74.3% (95% CI: 58.8-89.8%) and 68.2% (95% CI: 51.9-84.5%) in the VEN+HAA group, and 38.1% (95% CI: 0.9-75.3%) and 35.0% (95% CI: 3.6-66.4%) in the VEN+HAD group, respectively(OS: p=0.37; EFS: p=0.41). Conclusion 7-day VEN combined with intensive chemotherapy is an effective and safe induction therapy for high-risk AML patients. 【Keywords】Venetoclax; Chemotherapy; AML; Induction treatment；High-risk