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Enasidenib

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Small Molecules in Hematology

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 212))

Abstract

Enasidenib is an orally available, selective, potent, small molecule inhibitor of mutant isocitrate dehydrogenase 2 (IDH2). Neomorphic mutations in IDH2 are frequently found in both hematologic malignancies and solid tumors and lead to the production of the oncometabolite (R)-2-hydroxyglutarate. Increased levels of (R)-2-hydroxyglutarate cause histone and DNA hypermethylation associated with blocked differentiation and tumorigenesis. In PDX mice transplanted with human IDH2-mutant acute myeloid leukemia cells, enasidenib treatment led to normalization of (R)-2-hydroxyglutarate serum levels, differentiation of leukemic blasts and increased survival. Early clinical data in patients with relapsed/refractory IDH2-mutant acute myeloid leukemia show that enasidenib is well tolerated and induces durable complete remissions as a single agent in about 20% of cases. One notable drug-related adverse effect is differentiation syndrome. On the basis of these results the compound has recently been approved for the treatment of relapsed/refractory IDH2-mutant acute myeloid leukemia in the USA. Although no data are available yet, clinical trials on the treatment of patients with several types of IDH2-mutant solid tumors including gliomas, chondrosarcomas and cholangiocarcinomas are currently being performed.

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Authors and Affiliations

  1. Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ), University of Heidelberg, Heidelberg, Germany

    Alwin Krämer & Tilmann Bochtler

  2. Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany

    Alwin Krämer & Tilmann Bochtler

Authors
  1. Alwin Krämer
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  2. Tilmann Bochtler
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Correspondence to Alwin Krämer .

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Editors and Affiliations

  1. MOLIT Institute, Cancer Center Heilbronn-Franken, SLK-Clinics, Heilbronn, Baden-Württemberg, Germany

    Uwe M. Martens

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Krämer, A., Bochtler, T. (2018). Enasidenib. In: Martens, U. (eds) Small Molecules in Hematology. Recent Results in Cancer Research, vol 212. Springer, Cham. https://doi.org/10.1007/978-3-319-91439-8_9

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  • DOI: https://doi.org/10.1007/978-3-319-91439-8_9

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-91438-1

  • Online ISBN: 978-3-319-91439-8

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