Published Paper Details:

Acute myeloid leukemia is a malignancy of proliferative, abnormally, or poorly differentiated cells of the hematopoietic system, characterized by genetic heterogeneity. FMS-like tyrosine kinase 3- internal tandem duplication remains one of the most frequently mutated genes in acute myeloid leukemia, especially in those with normal cytogenetics. The FMS-like tyrosine kinase 3- internal tandem duplication and FLT3 tyrosine kinase domain mutations are biomarkers for high-risk acute myeloid leukemia and are associated with drug resistance and high risk of relapse. Various FLT3 inhibitors are in clinical development, including lestaurtinib, tandutinib, quizartinib, midostaurin, gilteritinib, and crenolanib. Gilteritinib is a small molecule that inhibits multiple receptor tyrosine kinases that also act as FMS-like tyrosine kinase 3. Gilteritinib, a next-generation tyrosine kinase inhibitor, is approved in several countries worldwide for the treatment of relapsed or refractory acute myeloid leukemia in adults with FMS-like tyrosine kinase 3 mutations. Gilteritinib demonstrated the ability to inhibit FLT3 receptor signaling and production in cells exogenously expressing FLT3 including FLT3 internal tandem duplication and tyrosine kinase domain mutations FLT3-D835Y and FLT3-ITD-D835Y, and it induced apoptosis in leukemic cells possessing FLT3 internal tandem duplication. In conclusion, gilteritinib therapy led to higher percentages of patients with the response and longer survival than salvage chemotherapy among patients with relapsed or refractory FLT3-mutated acute myeloid leukemia.