Positive single-centre experience with FLT3i in the allo-HCT setting

A real-world, single-centre experience confirmed that FLT3 inhibitors (FLT3i) can be safely integrated into the treatment of acute myeloid leukaemia (AML) in the context of allogeneic hematopoietic stem cell transplantation (allo-HCT). Importantly, FLT3i therapy did not impair engraftment or significantly increase the risk of graft-versus-host disease (GvHD) in this study.

The study was conducted at the San Gerardo Hospital in Monza, Italy, and presented by PhD student Francesca Duca (University of Milano-Bicocca, Italy) [1]. Ms Duca and colleagues retrospectively analysed 17 patients with FLT3-mutated AML, who underwent HCT and received FLT3i therapy before and/or after transplantation. Clinical efficacy, impact on graft function, and tolerability were assessed.

The 17 patients were divided into 4 treatment groups, with the following efficacy outcomes observed:

Post-transplant maintenance with sorafenib after complete remission (n=10): median overall survival (OS) was 22.5 months (range 10–99), while median progression-free survival (PFS) was 20 months (range 3–75). Two patients relapsed during or after maintenance therapy and subsequently received gilteritinib. After a median follow-up of 23 months, 8 patients remained alive.
Gilteritinib as second-line bridging therapy to transplant in refractory/relapsed (R/R) disease (n=3): all patients successfully proceeded to transplantation and maintained durable remissions when gilteritinib was continued post-HCT. Median OS was 44 months (range 11–53), and median PFS was 38 months (range 11–50). At the time of reporting, all patients remained in complete remission.
Patients treated after post-transplant relapse without prior FLT3i maintenance (n=2): outcomes were poor, with a median OS of 16.5 months (range 14–19) and a median PFS of 6.5 months (range 4–9). Neither patient survived.
Complex treatment pathways with sequential FLT3i exposure (n=2): both patients received azacitidine, venetoclax, and sorafenib; 1 patient for R/R AML before HCT with continuation of sorafenib post-transplant, and the other following relapse 1 year after HCT. After 5 months, the second patient switched to gilteritinib following a second relapse and achieved a third remission. Both patients remained alive after a median follow-up of 32 months.

FLT3i therapy administered before transplantation did not compromise engraftment in any treatment group. The incidence of acute GvHD ranged from 20% to 50%. The most common grade 3–4 toxicities were cytopenias, which were manageable with dose modifications. One case of myopericarditis was reported in group 4. Overall, approximately half of all participants experienced infections, all of which were manageable with standard therapy.

The authors concluded that sorafenib maintenance was associated with low relapse rates and favourable survival outcomes, while gilteritinib effectively bridged refractory patients to transplantation. The unfavourable outcomes observed in group 3 further supported the early use of FLT3i therapy.

Duca F, et al. Targeting FLT3: a real-life, single-center analysis of FLT3 inhibitors use in the allogeneic transplant setting. P257, EBMT congress 2026, 22-25 March, Madrid, Spain.