7-Day Venetoclax Combined with Intensive Chemotherapy As Induction Treatment in Newly Diagnosed Acute Myeloid Leukemia

INTRODUCTION The combination of Venetoclax (VEN) and intensive chemotherapy (IC) as an induction treatment has demonstrated notable effectiveness in the treatment of newly diagnosed acute myeloid leukemia (AML). Nevertheless, the precise duration of VEN therapy remains uncertain, leading to variability in its application during induction therapy. Given the risk of adverse events and the cost of treatment, it is important to define the optimal duration of VEN. Herein, we reported the data of 247 newly diagnosed AML patients who received 7-day VEN combined with IC (DA, HAA, or HAD) as induction treatment, to further validate the efficacy and safety of this combination. METHODS The patients included in this study were derived from two clinical trials (VEN+DA: ChiCTR2200061524; VEN+HAA: NCT05893472) 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 2.5mg/m2/day d3-7, Ara-c 100 mg/m²/day d3-7, and Acla 20mg/day d3-7), or HAD regimen (HHT 2mg/m2/day d2-6, DNR 45 mg/m²/day d 4-5, and Ara-c 100 mg/m²/day d2-6). After achieving complete remission (CR), allogeneic hematopoietic stem-cell transplantation (allo-HSCT) were recommended according to ELN guidelines. Patients who did not need or 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 de novo AML. The secondary objectives were to evaluate overall survival (OS) and event-free survival (EFS). RESULTS Between January 2022 and June 2024, a total of 247 de novo patients were enrolled and treated with VEN combined with IC as induction therapy. The median age was 43 (range, 14-60) years, and 142 (57.5%) patients were male. Among them, 108 patients underwent treatment with VEN+DA, 105 patients received VEN+HAA, and 34 patients were treated with VEN+HAD. The cCR(CR+CRi) rate in the entire cohort was 92.1% (95% CI, 88.7-95.5%), and the MRD negetive rate was 93.7% (95% CI, 90.3-97.0%) by flow cytometry. Comparing treatment subgroups, the cCR rates were 92.3% (95% CI, 87.1-97.5%) for VEN+DA, 93.2% (95% CI, 88.3-98.1%) for VEN+HAA, and 88.2% (95% CI, 76.8-99.6%) for VEN+HAD (p=0.645) and MRD negtive rates were 91.9% (95% CI, 86.0-97.8%), 98.9% (95% CI, 96.6-101.1%), and 84.8% (95% CI, 71.9-97.8%), respectively (p=0.013). The most frequent adverse effects were neutropenia (100%), thrombocytopenia (100%) and pneumonia (56.5%). The median recovery time for neutrophils and platelets were 13(range:5-52) and 13(range:4-63) days, respectively. Until June,30, 2024, with a median follow-up of 11 (0.5-29) months, 18.3% of patients underwent allo-HSCT (12.0% in VEN+DA, 18.1% in VEN+HAA, and 35.3% in VEN+HAD, p=0.012). The median OS and EFS were not reached. The estimated 12-month OS and EFS were 80.7% (95% CI: 75.3-86.4%) and 77.4% (95% CI: 71.6-83.6%) in the entire cohort, 80.1% (95% CI: 72.2-89.0%) and 77.0% (95% CI: 68.6-86.4%) in the VEN+DA group, 77.3% (95% CI: 68.8-86.9%) and 76.0% (95% CI: 67.3-86.0%) in the VEN+HAA group, and 88.6% (95% CI: 77.2-100.0%) and 84.6% (95% CI: 71.7-99.8%) in the VEN+HAD group, respectively(OS: p=0.36; EFS: p=0.53). CONCLUSION 7-day VEN combined with intensive chemotherapy is a highly effective and safe induction therapy for adults with newly diagnosed AML. Keywords Venetoclax; Chemotherapy; Acute myeloid leukemia; Induction treatment Disclosures No relevant conflicts of interest to declare.