吉瑞替尼 (Xospata)

概览

Gilteritinib is an AXL receptor tyrosine kinase inhibitor used to treat relapsed or refractory acute myeloid leukemia.

作用机制

Gilteritinib is a potent selective inhibitor of both of the mutations, internal tandem duplication (ITD) and tyrosine kinase domain (TKD), of the FLT3 receptor. In the same note, gilteritinib also inhibits AXL and ALK tyrosine kinases. FLT3 and AXL are molecules involved in the growth of cancer cells. The activity of gilteritinib permits an inhibition of the phosphorylation of FLT3 and its downstream targets such as STAT5, ERK and AKT. The interest in FLT3 transmembrane tyrosine kinases was raised when studies reported that approximately 30% of the patients with acute myeloid leukemia presented a mutationally activated isoform. As well, the mutation ITD is associated with poor patient outcomes while the mutation TKD produces a resistance mechanism to FLT3 tyrosine kinase inhibitors and the AXL tyrosine kinase tends to produce a resistance mechanism to chemotherapies.

适应症

Gilteritinib is indicated for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia with an FLT3 mutation detected by an FDA-approved test. This indication was expanded for a companion diagnostic to include use with gilteritinib such as the LeukoStrat CDx FLT3 Mutation Assay. Acute myeloid leukemia is cancer that impacts the blood and bone marrow with a rapid progression. This condition produces low numbers of normal blood cells and the requirement of continuous need for transfusions.

• Relapsed or Refractory Acute Myeloid Leukemia With FLT3 Activating Mutations