Acute myeloid leukemia patients with myelodysplasia-related gene mutations benefit from post-transplant hypomethylating agent maintenance

Relapse remains the major cause of mortality in adverse-risk acute myeloid leukemia (AML) patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). Hypomethylating agent (HMA) maintenance is a strategy to prevent post-transplant relapse, but its value among different genetically defined subgroups is still controversial. The study was designed to evaluate the efficacy of HMA maintenance in adverse-risk AML. In this retrospective, multicenter study, consecutive adverse-risk AML patients who received allo-HSCT between January 2017 and April 2023 were screened, with 469 patients ultimately included for analysis. These patients were divided into a HMA maintenance treatment group (MT group, n = 136) and a nonmaintenance group (NMT group, n = 333). Adverse-risk patients transplanted in first complete remission (CR1) pre-HSCT had significantly better 3-year transplant outcomes compared to those in non-CR1. Baseline characteristics of patients in the MT and NMT groups were well balanced except for conditioning regimen, with more patients in the MT group receiving myeloablative conditioning (94.1% versus 76.0%, P < .001). HMA maintenance reduced the 3-year cumulative incidence of relapse (19.2% versus 34.0%, P = .026) and improved the 3-year probabilities of event-free survival (EFS) (68.6% versus 43.4%, P < .001), relapse-free survival (69.1% versus 48.6%, P = .001), and overall survival (72.1% versus 61.0%, P = .034). The benefit of HMA maintenance was most evident in AML patients with myelodysplasia-related gene mutations (e.g., for EFS, hazard ratio 0.47, P = .002), and those receiving allo-HSCT in first remission and with undetectable measurable residual disease might not benefit from this strategy. Meta-analysis indicated that treatment efficacy across different centers was comparable. Our findings reported the specific subgroups of adverse-risk AML patients who might benefit from post-transplant HMA maintenance.