Abstract
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is potentially the only curative option for high-risk acute myeloid leukemia (AML) patients. However, disease relapse remains the principal cause of treatment failure of these patients, and outcomes of salvage treatments are poor. This research seeks to evaluate the efficacy and safety of a dual epigenetic targeting maintenance therapy with chidamide and azacitidine (AZA) in patients with high-risk AML post-allo-HSCT. METHODS: This multicenter, open-label, phase 2 prospective clinical trial (ChiCTR2300067593) recruited and followed up 48 patients diagnosed with high-risk AML post-allo-HSCT from 3 hospitals in China from November 2021 to March 2024. Chidamide (5 mg) was administered orally once daily for 5 days, combined with AZA (75 mg/m(2)) subcutaneously daily for 5 days, respectively. Treatment started as early as 3 months after transplantation. All patients were in complete remission before each maintenance cycle. A total of 6 cycles was recommended. RESULTS: The 2-year cumulative incidence of relapse (CIR) was 8.4% (95% CI 4.4-12.4%), 2-year relapse-free survival (RFS) was 91.6% (95% CI 87.6-95.6%), and overall survival (OS) was 97.9% (95% CI 95.8-100%). At the end of the follow-up period, 4 patients relapsed, of which 1 patient died of leukemia recurrence; the other three patients underwent second allo-HSCT and are still alive in remission. The most common adverse events (AEs) were hematological toxicity. No grade > 3 AEs were noted. Graft-versus-host disease (GVHD) occurred in 29.2% (14/48) of patients. Six cases (6/48, 12.5%) were complicated with infection. No treatment-related mortality occurred. CONCLUSIONS: Dual epigenetic targeting maintenance treatment with CHI-AZA has an acceptable toxicity profile and might potentially be effective to prevent relapse in high-risk AML patients after allo-HSCT. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2300067593. Registered January 12, 2013.