Durable remission for more than 5 years with gilteritinib in FLT3-ITD-positive acute myeloid leukemia relapsing after a second allogeneic transplantation

Acquired resistance to FLT3 inhibitors remains a major challenge in FLT3 -mutated acute myeloid leukemia (AML). We report a 44-year-old man with NPM1 -mutated AML who developed FLT3 -ITD at hematological relapse after cord blood transplantation. The patient underwent a second allogeneic hematopoietic stem cell transplantation while receiving quizartinib as salvage therapy, followed by post-transplant quizartinib maintenance. Hematological relapse occurred during maintenance approximately 3 months after the second transplantation. The LeukoStrat CDx FLT3 Mutation Assay detected an FLT3 tyrosine kinase domain mutation in addition to FLT3 -ITD, prompting a switch from quizartinib to gilteritinib. The subsequent FoundationOne Heme report characterized the tyrosine kinase domain alteration as FLT3 -D835V. Retrospective comparison of results from specimens collected before quizartinib initiation, before the second transplantation, and at relapse during quizartinib maintenance showed that D835V was not detected in the two earlier specimens. Gilteritinib induced complete remission without additional intensive chemotherapy or donor lymphocyte infusion, and the patient has remained in remission for more than 5 years. This case illustrates the complementary value of clinical FLT3 testing for treatment selection and retrospective comparison of serial genomic findings for characterizing relapse.