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FLT3-Inhibitoren in der Therapie der akuten myeloischen Leukämie

FLT3 inhibitors for the treatment of acute myeloid leukemia

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Zusammenfassung

Die Aktivierung des FLT3-Tyrosinkinaserezeptors spielt eine entscheidende Rolle in der Pathogenese der akuten myeloischen Leukämie (AML). Seit über einem Jahrzehnt sind Medikamente in Erprobung, die diesen Rezeptor samt den nachgeschalteten onkogenen Signalwegen hemmen und somit die generell schlechte Prognose der AML verbessern sollen. Mit Midostaurin ist seit Kurzem ein Inhibitor für die Erstlinientherapie der AML mit FLT3-Mutation in Kombination mit Standardchemotherapie zugelassen. Für weitere Inhibitoren wird mit einer Zulassung für die therapierefraktäre bzw. rezidivierte AML in Kürze gerechnet. In der vorliegenden Arbeit werden die aktuellen Daten und Hintergründe zur Tyrosinkinaseinhibitortherapie bei der FLT3-mutierten AML diskutiert und zukünftige Entwicklungen präsentiert. Entscheidend für die weitere Bewertung der einzelnen Inhibitoren zur Behandlung der AML mit FLT3-Mutation ist die konsequente Erfassung und Untersuchung von Patienten im Rahmen von randomisierten Studien bzw. Registerstudien.

Abstract

The activation of the FLT3 tyrosine kinase receptor plays an essential role in the pathogenesis of acute myeloid leukemia (AML). For more than a decade, drugs that inhibit this receptor and its downstream oncogenic signaling pathways have been in development. These tyrosine kinase inhibitors (TKIs) are used to improve the generally dismal prognosis of AML. Recently, midostaurin has been approved for first-line treatment of FLT3-mutated AML in combination with standard chemotherapy. Novel TKIs are in clinical development and are most likely to be approved for refractory or recurrent AML in the near future. In this review, the authors present the background and current data on TKI treatment in FLT3-mutated AML and discuss their clinical impact and future developments. Apart from clinical trial results, the consequent documentation and evaluation of clinical routine outcomes in registries is essential to define the role and significance of TKIs in the treatment of AML.

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  1. Klinik für Innere Medizin SP Hämatologie, Onkologie und Immunologie, Universitätsklinikum Gießen und Marburg, Philipps-Universität Marburg, Marburg, Deutschland

    Stephan Metzelder

  2. Medizinische Klinik und Poliklinik, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Deutschland

    Christoph Röllig

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C. Röllig weist auf folgende Beziehungen hin: Er erhielt Forschungsförderung von Abbvie, Bayer, Celgene und Novartis sowie Honorare für Beratungsleistungen von Abbvie, Amgen, BMS, Celgene, Daiichy Sankyo, Janssen, Jazz, Novartis, Pfizer, Roche und Takeda. S. Metzelder gibt an, dass kein Interessenkonflikt besteht.

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Metzelder, S., Röllig, C. FLT3-Inhibitoren in der Therapie der akuten myeloischen Leukämie. best practice onkologie 13, 182–190 (2018). https://doi.org/10.1007/s11654-018-0087-5

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