The European Medicines Agency Review of Gilteritinib (Xospata) for the Treatment of Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia with an FLT3 Mutation

The oncologist

article

Kyriaki Tzogani¹  Bjørg Bolstad²  Irēna Rogovska²  Natalja Karpova²  Harald Enzmann²  Christian Gisselbrecht⁶  Francesco Pignatti¹  Hilde Røshol²  Helga Haugom Olsen²  Ida B. Aas²  Marianne Løiten Dalhus²  Gro Dahlseng Håkonsen²  Laila Sortvik Nilssen²  Vibeke Lindberg²  Mats Økvist² 

[1] European Medicines Agency;Committee for Medicinal Products for Human Use (CHMP);Statens legemiddelverk;Zāļu valsts aǵentūra;Bundesinstitut für Arzneimittel und Medizinprodukte;Hospital Saint Louis

关键词: Gilteritinib (Xospata);    Acute myeloid leukemia;    Fms-like tyrosine kinase 3;    European Medicines Agency;   

DOI  :  10.1634/theoncologist.2019-0976

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

On October 24, 2019, a marketing authorization valid through the European Union (EU) was issued for gilteritinib monotherapy for adult patients who have relapsed or refractory acute myeloid leukemia (AML) with an Fms-like tyrosine kinase 3 (FLT3) mutation. Gilteritinib inhibits FLT3 receptor signaling and proliferation in cells exogenously expressing FLT3 including FLT3 internal tandem duplication (ITD), FLT3 D835Y, and FLT3 ITD D835Y, and it induced apoptosis in leukemic cells expressing FLT3 ITD. The recommended starting dose of gilteritinib is 120 mg (three 40 mg tablets) once daily. Gilteritinib was evaluated in one, phase III, open-label, multicenter, randomized study of gilteritinib (n = 247, gilteritinib arm) versus salvage chemotherapy (n = 124, salvage chemotherapy arm) in patients with relapsed or refractory AML with FLT3 mutation. Overall survival (OS) was statistically significantly different between the two groups with a median OS of 9.3 months in the gilteritinib arm compared with 5.6 months for salvage chemotherapy (hazard ratio, 0.637; 95% confidence interval, 0.490–0.830; p = .0004 one-sided log-rank test). The most common adverse reactions with gilteritinib treatment were blood creatine phosphokinase increase, alanine aminotransferase increase, aspartate aminotransferase increase, blood alkaline phosphatase increase, diarrhea, fatigue, nausea, constipation, cough, peripheral edema, dyspnea, dizziness, hypotension, pain in extremity, asthenia, arthralgia, and myalgia. The objective of this article is to summarize the scientific review of the application leading to regulatory approval in the EU.

【 授权许可】

CC BY|CC BY-NC