The European Commission (EC) issued a marketing authorization for gilteritinib on October 24, 2019, after receiving approval from the Committee for Medicinal Products for Human Use (CHMP). It is a scientific committee of the European Medicines Agency (EMA). The permission is valid throughout the European Union. Gilteritinib (Brand name: Xospata) is to be used as monotherapy for adult patients who have relapsed or refractory acute myeloid leukemia (AML) with an Fms-like tyrosine kinase 3 (FLT3) mutation. The FLT3 receptor signaling and proliferation in cells exogenously expressing FLT3, including FLT3 internal tandem duplication (ITD), FLT3 D835Y, and FLT3 ITD D835Y is hindered by gilteritinib. It also induces apoptosis in leukemic cells expressing FLT3 ITD. 120 mg (three 40 mg tablets) once daily is the suggested starting dosage of gilteritinib. One, phase III, open-label, multicenter, randomized study of gilteritinib (n=247) against salvage chemotherapy (n=124) in patients with relapsed or refractory AML with FLT3 mutation was used to assess gilteritinib. Statistically, overall survival (OS) was considerably diverse between the two groups. The gilteritinib arm showed a median OS of 9.3 months whereas salvage chemotherapy showed a median OS of 5.6 months (hazard ratio, 0.637; 95% confidence interval, 0.490–0.830; p=0.0004 one-sided log-rank test). Increase in blood creatine phosphokinase, increase in alanine aminotransferase, increase in aspartate aminotransferase, increase in blood alkaline phosphatase, diarrhea, fatigue, nausea, constipation, cough, peripheral edema, dyspnea, dizziness, hypotension, pain in extremity, asthenia, arthralgia, and myalgia were some of the most usual unfavorable reactions after gilteritinib was administered. The goal of the study is to recapitulate the scientific review by CHMP that lead to the EC’s regulatory approval in the EU.

 

Link:theoncologist.onlinelibrary.wiley.com/doi/10.1634/theoncologist.2019-0976