Chidamide-based epigenetic therapy for relapsed/refractory Acute Myeloid Leukemia

Abstract Introduction: Effective treatment options for relapsed or refractory acute myeloid leukemia (R/R AML) remain limited. Methods: We conducted a multicenter, prospective phase II study (registration number: ChiCTR2300073732) to evaluate the efficacy and safety of the following combination regimens in patients with R/R AML: chidamide combined with a hypomethylating agent (decitabine or azacitidine) combined with daunorubicin and cytarabine, or combined with the HA regimen, or combined with venetoclax. We used patients previously treated with the DA regimen as a historical control group to compare the efficacy and safety of each regimen. Results: A total of 13 Asian Chinese subjects were enrolled in this study, including 9 males (69.2%) and 4 females (30.8%). The age range was 19 to 85 years old, with the youngest being 19 years old and the oldest being 85 years old, and the median age was 49 years old. 8 patients received chidamide combined with a hypomethylating agent (decitabine or azacitidine) plus daunorubicin and cytarabine or the HA regimen; the other 5 received chidamide combined with a hypomethylating agent (decitabine or azacitidine) and venetoclax. Among these 13 patients, the complete remission (CR) rate was 53.8%, and the partial remission (PR) rate was 7.7%. Among the 8 patients who received dual epigenetic therapy combined with chemotherapy, the CR rate was 37.5%, the PR rate was 12.5%, and the CR rate was 80% among the 5 patients who received dual epigenetic therapy combined with venetoclax. Discussion: This study suggests that chidamide combined with a hypomethylating agent shows promising activity in R/R AML, with a CR rate up to 53.8%. The addition of venetoclax further improved outcomes, achieving an 80% CR rate in the venetoclax group. These results indicate a potential synergistic effect and support further evaluation of this triple combination in larger clinical studies.