Treatment sequence with gilteritinib and allogeneic haematopoietic stem cell transplantation in relapsed/refractory FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukaemia patients: A multicentre real-world study.

Patients with relapsed or refractory acute myeloid leukaemia (r/r AML) harbouring FMS-like tyrosine kinase 3 (FLT3) mutations generally have poor prognosis and limited treatment options. The second-generation FLT3 inhibitor gilteritinib provides better disease control compared to standard relapse therapies and was approved based on two randomized trials. We analysed its efficacy and safety in a real-world cohort of r/r AML patients undergoing gilteritinib treatment including allogeneic haematopoietic stem cell transplantation (alloHSCT). Data were collected from all consecutive r/r AML patients with FLT3-internal tandem duplication and/or FLT3-tyrosine kinase domain mutations receiving gilteritinib at 25 centres. Response and survival were analysed using descriptive and correlative statistics. A total of 156 patients were analysed, 55.1% with relapse after previous alloHSCT, and 46.2% with prior FLT3 inhibitor exposure. The overall complete remission/incomplete remission (CR/Cri) rate was 45.3%, with a median overall survival (OS) of 10.0 months. Patients receiving gilteritinib only had a 1-year OS of 34%, while those with consolidating alloHSCT had a 1-year OS of 76%-92%, depending on gilteritinib maintenance post-transplant. Resuming gilteritinib post-transplant led to an 85.7% CR/CRi rate. Our real-world data confirm that gilteritinib is an effective single-agent therapy for r/r AML with FLT3 mutations, with best outcomes when used as a bridge to transplant and post-transplant maintenance.