Introduction: Mutations in the gene encoding for the FMS-like tyrosine kinase 3 (FLT3) are present in about 30% of adults with AML and are associated with shorter disease-free and overall survival after initial therapy. Prognosis of relapsed/refractory AML with FLT3 mutations is even more dismal with median overall survival of a few months only. Areas covered: This review will cover current and emerging treatments for relapsed/refractory AML with FLT3 mutations, preclinical rationale and clinical trials with new encouraging data for this particularly challenging population. The authors discuss mechanisms of resistance to FLT3 inhibitors and how these insights serve to identify current and future treatments. As allogeneic stem cell transplant in the first remission is the preferred therapy for newly diagnosed AML patients with FLT3 mutations, the authors discuss the role of maintenance after SCT for the prevention of relapse. Expert opinion: Relapsed/refractory AML with FLT3 mutations remains a therapeutic challenge with currently available treatments. However, the evolution of targeted therapies with next-generation FLT3 inhibitors and their combinations with chemotherapy is showing much promise. Moreover, growing understanding of the pathways of resistance to treatment has led to the identification of various targeted therapies currently being explored, which in time will improve outcomes.
Keywords: inhibitors; mutated; Relapsed/refractory acute myeloid leukemia; novel targeted therapies.