MRD-Driven Prophylactic or Pre-Emptive Intervention with Chidamide-Based Treatment for High-Risk AML Relapse Post-Transplantation: A Real-World Experience from a Chinese Single Center

Background: The persistence of measurable residual disease (MRD) at the time of transplantation or post-transplantation is widely recognized as the most significant risk factor for relapse and poor outcomes in patients with acute myeloid leukemia (AML). Although azacitidine (AZA), Chidamide, and inhibitors targeting FLT3, IDH1/2, and KIT have been employed to mitigate post-transplant relapse, their efficacy remains suboptimal. The potential of MRD-driven prophylactic and pre-emptive interventions to improve relapse prevention in AML warrants investigation. This study evaluates the efficacy and safety of MRD-driven prophylactic or pre-emptive treatment with Chidamide-based treatment in 49 post-transplant AML patients at a single center. Aim: To assess the 6-month and 1-year MRD-negative and relapse-free survival (RFS) rates in high-risk AML patients treated with Chidamide-based treatment post-transplantation. Methods: Between December 2020 and January 2024, 49 AML patients received Chidamide or Chidamide combined with HMA as prophylactic or pre-emptive intervention to prevent post-transplant relapse. The cohort included 22 males and 27 females, with a median age of 38 years (range: 17-62). Among them, 46 patients had de novo AML, and 3 had secondary AML (sAML). According to the European LeukemiaNet (ELN) 2022 prognostic stratification, 10 patients were categorized as favorable-risk, 24 as intermediate-risk, and 15 as adverse-risk. In this study, 27 cases with ELN adverse-risk, pre-transplant MRD positivity, or relapse who converted to MRD-negative status post-transplant received prophylactic treatment, while those remaining 22 cases MRD-positive post-transplant received pre-emptive treatment. The specific regimen included Chidamide administered orally at 5 mg per day, six times per week, for at least one year post-engraftment, AZA 50 mg/m² on days 1-5 of each month for six months. Results: In this cohort of 49 patients, the median follow-up period was 738 days (range: 168-2349 days). The MRD-free survival rate, RFS rate, and overall survival (OS) rate were 53.1%, 65.3%, and 73.5%, respectively. At 6 months, the MRD-free survival, RFS, and OS rates were 77.6%, 79.6%, and 98%, respectively. At 1 year, the MRD-free survival, RFS, and OS rates were 63.3%, 73.5%, and 81.6%, respectively. In the prophylactic intervention group, the overall relapse incidence rate in MRD-negative patients was 31.8%, with a median time of 285 days (range: 72-857 days) from treatment initiation to the first observed MRD positivity. These findings underscore that the Chidamide-based regimen resulted in a high rate of MRD-negative responses in high-risk AML patients. In the pre-emptive intervention cohort, the overall MRD conversion rate from MRD-positive to MRD-negative was 85.2%, with a median time of 52 days from treatment initiation to the first observed MRD-negative assessment and a median duration of MRD negativity of 563 days (range: 24 days to unreached). Among responders, the relapse incidence in the MRD-positive group was 30.4%. Patients receiving Chidamide monotherapy or Chidamide combined with HMAs achieved a significantly higher rate of MRD negativity compared to those receiving other combination therapies (90% vs. 100% vs. 40%, P=0.006; Figure 1). No significant difference in relapse incidence was observed among MRD-positive responders (P=0.391). Reversible grade 3/4 neutropenia occurred in 34.7% of patients, and thrombocytopenia was observed in 18.4% during the first four treatment cycles. Two patients developed grade 3/4 infections, and one experienced grade 3/4 diarrhea, all of which resolved following treatment. There were no statistically significant differences in adverse event rates among the three treatment groups (monotherapy 41.4%, combination with HMAs 60%, combination with other drugs 80%, P=0.198). No new-onset graft-versus-host disease (GVHD) was reported in patients without a prior history of GVHD during Chidamide treatment. Conclusion: The Chidamide±AZA regimen is a safe and effective prophylactic or pre-emptive intervention for high-risk AML patients following transplantation. Whether used as monotherapy or in combination with HMAs, Chidamide demonstrates significant efficacy in eliminating MRD, warranting further clinical research (registration number: NCT06066905). Disclosures: The authors declare no relevant conflicts of interest.