A clinical case report in Annals of Hematology describes a 44-year-old man with relapsed acute myeloid leukemia who achieved complete remission lasting more than five years after switching to gilteritinib for an acquired FLT3 tyrosine kinase domain mutation. The patient’s disease progressed during FLT3 inhibitor quizartinib maintenance following a second allogeneic transplant, with serial genomic profiling identifying the FLT3-D835V alteration emerging during maintenance. After the therapeutic switch to gilteritinib—guided by FLT3 testing—the patient did not require donor lymphocyte infusions or additional intensive chemotherapy and remained in continuous remission beyond five years. The report highlights the practical value of serial genomic profiling to characterize mechanisms of relapse and support salvage strategy selection in FLT3-driven AML.