BACKGROUND: Relapse remains a major challenge limiting long-term survival in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Measurable residual disease (MRD) is a critical independent prognostic predictor in high-risk AML. While MRD-driven prophylactic or preemptive interventions hold promise for relapse prevention, optimal therapeutic strategies remain lacking. We investigated the efficacy and safety of chidamide, a selective histone deacetylase (HDAC) inhibitor with dual epigenetic and immunomodulatory properties, within MRD-adapted post-transplant strategies in high-risk AML. METHODS: This pilot study analyzed 43 consecutive AML patients with high-risk AML, including pre-transplant relapsed/refractory or MRD-positive, or post-transplant MRD-positive who received Chidamide-based therapy after allo-HSCT between December 2020 and July 2023. Patients who were MRD-negative post-transplant (n=17) received prophylactic therapy, while those who were MRD-positive or relapsed post-transplant (n=26) underwent preemptive intervention. Primary endpoints included relapse-free survival (RFS) and overall survival (OS). Secondary endpoints included MRD negativity rates, toxicity (CTCAE v5.0), and changes in peripheral blood lymphocyte subsets. Statistical analyses employed Kaplan-Meier methods and Log-rank tests for survival, Chi-square/Fisher's exact tests for categorical variables, and paired t-tests for lymphocytes subsets. RESULTS: At a median follow-up of 742 days, the overall sustained remission rate was 60.4%. In the preemptive group, Chidamide-based therapy achieved an 88.5% MRD conversion rate from positive to negative (median time to conversion: 50 days), with 65% maintaining sustained negativity. The prophylactic group demonstrated a 58.8% sustained MRD-negative rate. The 6-month and 1-year RFS and OS rates for the entire cohort were 79%, 69.8% and 100%, 72.1%, respectively. No statistically significant difference in RFS or OS was observed between the preemptive and prophylactic groups (P>0.05 for both). Grade 3/4 hematologic toxicities occurred in 32.6% (neutropenia) and 20.9% (thrombocytopenia) of patients, with no GVHD exacerbation observed. Chidamide treatment significantly increased peripheral blood CD8+ T cells (P=0.033) while reducing CD4+ T cells (P=0.007), suggesting enhanced cytotoxic potential. CONCLUSION: Chidamide-based MRD-driven therapy demonstrates promising durable MRD eradication and clinically relevant survival rates in high-risk AML patients post transplant, potentially mediated by its dual epigenetic and immunomodulatory effects, including T-cell modulation. While limited by its retrospective nature and single-center design, these real-world findings support further investigation of HDAC inhibitor-based MRD-directed algorithms in prospective studies (NCT06066905).
Ling et al. (Mon,) studied this question.