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.

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  • Additional Information
    • Affiliation:
      European Medicines Agency, Amsterdam, The Netherlands
      Committee for Medicinal Products for Human Use (CHMP), Amsterdam, The Netherlands
      Statens legemiddelverk, Oslo, Norway
      Zāļu valsts aǵentūra, Riga, Latvia
      Bundesinstitut für Arzneimittel und Medizinprodukte, Bonn, Germany
      Hospital Saint Louis, Paris, France
    • Subject Terms:
    • Subject Terms:
    • Abstract:
      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. Implications for Practice: Xospata was approved in the European Union as monotherapy for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an Fms‐like tyrosine kinase 3 (FLT3) mutation. Gilteritinib resulted in a clinically meaningful and statistically significant improvement of overall survival compared with salvage chemotherapy. At the time of the marketing authorization of gilteritinib, there were no approved standard therapies specifically for adult patients diagnosed with relapsed or refractory AML with FLT3 mutation. In terms of safety, the overall accepted safety profile was considered manageable. This article addresses development and authorization of gilteritinib monotherapy for the treatment of acute myeloid leukemia with an FLT3 mutation, summarizing the scientific review of the application leading to regulatory approval in the European Union.
    • Journal Subset:
      Biomedical; Blind Peer Reviewed; Editorial Board Reviewed; Expert Peer Reviewed; Peer Reviewed; USA
    • ISSN:
      1083-7159
    • MEDLINE Info:
      NLM UID: 9607837
    • Publication Date:
      20200722
    • Publication Date:
      20200722
    • DOI:
      10.1634/theoncologist.2019-0976
    • Accession Number:
      144544222
  • Citations
    • ABNT:
      TZOGANI, K. et al. 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. Oncologist, [s. l.], v. 25, n. 7, p. e1070–e1076, 2020. DOI 10.1634/theoncologist.2019-0976. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=144544222. Acesso em: 27 set. 2020.
    • AMA:
      Tzogani K, Røshol H, Olsen HH, et al. 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. Oncologist. 2020;25(7):e1070-e1076. doi:10.1634/theoncologist.2019-0976
    • APA:
      Tzogani, K., Røshol, H., Olsen, H. H., Aas, I. B., Dalhus, M. L., Håkonsen, G. D., Nilssen, L. S., Lindberg, V., Økvist, M., Bolstad, B., Rogovska, I., Karpova, N., Enzmann, H., Gisselbrecht, C., & Pignatti, F. (2020). 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. Oncologist, 25(7), e1070–e1076. https://doi.org/10.1634/theoncologist.2019-0976
    • Chicago/Turabian: Author-Date:
      Tzogani, Kyriaki, Hilde Røshol, Helga Haugom Olsen, Ida B. Aas, Marianne Løiten Dalhus, Gro Dahlseng Håkonsen, Laila Sortvik Nilssen, et al. 2020. “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.” Oncologist 25 (7): e1070–76. doi:10.1634/theoncologist.2019-0976.
    • Harvard:
      Tzogani, K. et al. (2020) ‘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’, Oncologist, 25(7), pp. e1070–e1076. doi: 10.1634/theoncologist.2019-0976.
    • Harvard: Australian:
      Tzogani, K, Røshol, H, Olsen, HH, Aas, IB, Dalhus, ML, Håkonsen, GD, Nilssen, LS, Lindberg, V, Økvist, M, Bolstad, B, Rogovska, I, Karpova, N, Enzmann, H, Gisselbrecht, C & Pignatti, F 2020, ‘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’, Oncologist, vol. 25, no. 7, pp. e1070–e1076, viewed 27 September 2020, .
    • MLA:
      Tzogani, Kyriaki, et al. “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.” Oncologist, vol. 25, no. 7, July 2020, pp. e1070–e1076. EBSCOhost, doi:10.1634/theoncologist.2019-0976.
    • Chicago/Turabian: Humanities:
      Tzogani, Kyriaki, Hilde Røshol, Helga Haugom Olsen, Ida B. Aas, Marianne Løiten Dalhus, Gro Dahlseng Håkonsen, Laila Sortvik Nilssen, et al. “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.” Oncologist 25, no. 7 (July 2020): e1070–76. doi:10.1634/theoncologist.2019-0976.
    • Vancouver/ICMJE:
      Tzogani K, Røshol H, Olsen HH, Aas IB, Dalhus ML, Håkonsen GD, et al. 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. Oncologist [Internet]. 2020 Jul [cited 2020 Sep 27];25(7):e1070–6. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=144544222