Role of FLT3 inhibitors in post-HCT maintenance in AML reinforced

The 2-year leukaemia-free survival (LFS) with prophylaxis using a FLT3 inhibitor (FLT3i) exceeded 80% after allogeneic haematopoietic stem cell transplantation (allo-HCT) in patients with acute myeloid leukaemia (AML). These findings, derived from an EBMT registry-based multicentre analysis, further support the use of FLT3i therapy, particularly sorafenib, as standard post-HCT maintenance [1].

Relapse following transplantation remains frequent and continues to represent a major challenge in AML management. This non-randomised EBMT study aimed to evaluate the relative efficacy and safety of FLT3i compared with hypomethylating agents (HMAs), as well as the impact of patient selection, treatment timing, and treatment duration. The results were presented by Dr Nour Moukalled (American University of Beirut, Lebanon) [1].

The study included 317 adult AML patients in first complete remission who underwent HCT and received a FLT3i or HMA prophylaxis within 180 days post-transplantation, Dr Moukalled explained. Of these, 171 patients received a FLT3i (58% sorafenib, 30% midostaurin, and 11% gilteritinib), while 146 patients received HMA maintenance (92% azacitidine and 8% decitabine). As the study was non-randomised, significant between-group differences were observed, most notably in mutation status, cytogenetics, and treatment exposure before or after HCT.

FLT3i therapy was initiated at a median of 74 days post-HCT and continued for a median duration of 364 days. After a median follow-up of 3 years, the 2-year overall survival (OS) from the start of prophylaxis was 87% (95% CI 81–91%), while the 2-year LFS was 82% (95% CI 75–87%). These outcomes were not significantly influenced by age, measurable residual disease (MRD) status at HCT, prior FLT3i exposure, previous graft-versus-host disease (GvHD), or the specific FLT3i used. Stratified by FLT3i agent, the 2-year OS and LFS rates were 88% and 81% for sorafenib, 91% and 87% for midostaurin, and 70% and 70% for gilteritinib (P=0.13 and P=0.28, respectively). Importantly, the 2-year cumulative incidence of relapse was significantly higher in patients who were MRD-positive at transplantation compared with MRD-negative patients (21% vs 8%; P=0.03).

HMA maintenance also demonstrated encouraging outcomes, particularly in patients with prior GVHD. HMA therapy was initiated at a median of 69 days post-HCT and continued for a median of 172 days. The 2-year OS was 77% (95% CI 69–83%), while the 2-year LFS was 72% (95% CI 64–78%). Age, AML type, cytogenetic profile, and pre-transplant MRD status did not significantly influence these outcomes. However, prior GvHD before initiation of maintenance was associated with significantly improved OS and LFS:

2-year OS: 91% (95% CI 78–97%) versus 71% (95% CI 60–79%; P=0.03);
2-year LFS 85% (95% CI 72–93%) versus 66% (95% CI 55–74%; P=0.02).

Moukalled N, et al. Maintenance therapy post hematopoietic stem cell transplant in acute myeloid leukemia with FLT3 inhibitors and hypomethylating agents: insights from the EBMT Acute Leukemia Working Party. B289, EBMT congress 2026, 22-25 March, Madrid, Spain.