A prospective clinical study of venetoclax plus azacitidine for the maintenance treatment of post-remission Acute Myeloid Leukemia

Abstract

Abstract Introduction Although acute myeloid leukemia (AML) patients often achieve remission after induction therapy, most patients eventually relapse, highlighting a significant clinical need to reduce the risk of relapse. Oral azacitidine (AZA) (CC - 486) maintenance has shown improved overall and relapse-free survival (QUAZAR AML - 001 study). Additionally, a phase 2 study (NCT0406266) demonstrated the tolerability and feasibility of low-dose AZA combined with venetolax (VEN) as maintenance therapy in AML. AIM We plan a larger prospective study to further evaluate the efficacy and safety of AZA with VEN as maintenance therapy in remission-phase AML by optimizing the treatment interval. METHOD This prospective, multicenter, single-arm study enrolled adults (≥18 years) with non-APL AML in complete remission (CR) or CR with incomplete count recovery (CRi) after receiving at least 2 cycles of consolidation therapy, and confirmed MRD-negative status (flow cytometry threshold: 0.1%) within 3 months pre-enrollment. Patients were stratified into two cohorts: Cohort 1 (intensive induction chemotherapy) and Cohort 2 (low-intensity induction therapy). Patients received AZA 50 mg/m² IV/SQ D1–5 and VEN 400 mg PO D1–14 in 28-day cycles for 6 consecutive cycles, then every other cycle until 2 years (ELN2022 low-risk: 1 year). Primary endpoint was relapse-free survival (RFS). RESULTS As of August 2025, 67 patients were enrolled, with 35 assigned to cohort 1 (intensive induction chemotherapy) and 32 to cohort 2 (low-intensity induction). The full cohort comprised 33 (49%) males and 34 (51%) females, with a median age of 59 years (range 18–80). The median interval from complete remission (CR) to maintenance therapy initiation was 7.8 months (IQR 4.8–11.3). Patients received a median of 6 maintenance cycles (IQR 4–9), with a median follow-up of 17.9 months (IQR 11.2-22.8). The 12-month relapse-free survival (RFS) rate was 86.7% (95% CI 75.1%–93.1%) for the full cohort, 90.5% (95% CI 73.2%–96.8%) for cohort 1, and 82.5% (95% CI 62.9%–92.4%) for cohort 2. The median RFS was not reached in any cohort. During follow-up, 16 patients experienced relapse, among which 6 (17%) in cohort 1 and 10 (31%) in cohort 2 relapsed, while the remaining patients maintained remission. According to the ELN2022 risk stratification, 11 (73%) relapses occurred in the high-risk group, 3 (11%) in the intermediate-risk group, and 2 (8%) in the low-risk group. Notably, 2 high-risk patients in cohort 2 died due to recurrence. Treatment-emergent adverse events (TEAEs) occurred in 46 patients (69%), predominantly grade 1–2. The most frequent grade 3–4 TEAEs were neutrophil count decreased (n=22) and platelet count decreased (n=6). No treatment-related deaths or treatment discontinuations due to severe adverse events occurred. CONCLUSIONS VEN+AZA maintenance demonstrates promising RFS and manageable toxicity in remission-phase AML. Extended follow-up (target N=114) will further define survival benefits across different patient groups.