Dual Epigenetic Targeting with Chidamide and Azacitidine after Allogeneic Hematopoietic Stem Cell Transplantation for High-Risk Acute Myeloid Leukemia Patients

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. Azacitidine (AZA), a DNA methyltransferase inhibitor, shows anti-leukemia activity in myeloid diseases. Chidamide, a selective histone deacetylase inhibitor, effectively induces apoptosis in AML cells. When combined, these agents have a synergistic inhibitory effect on AML cells. A multicenter, prospective study (ChiCTR2300067593) was conducted with 48 high-risk AML patients after allo-HSCT. Patients received chidamide 5 mg/d plus azacitidine 75 mg/m²/d for 5 days. Additionally, 28 patients who received azacitidine alone as maintenance therapy after allo-HSCT were reviewed as a control group. With a median follow-up of 448 days (range 151–918), the chidamide plus azacitidine (CHI-AZA) regimen demonstrated superior 2-year relapse-free survival (RFS) (93.3% vs 71.6%, P = 0.039) and overall survival (OS) (96.3% vs 75.3%, P = 0.011) compared to AZA alone. The difference of 2-year cumulative incidence of relapse (CIR) was not significantly (6.7% vs 22.1%, P = 0.163). In conclusion, the CHI-AZA maintenance therapy could be an effective method to improve outcomes of high-risk AML patients after allo-HSCT.