Enasidenib for the treatment of acute myeloid leukemia.

Expert Review of Clinical Pharmacology
James Dugan, Daniel A Pollyea

Abstract

In August 2017, the United States Federal Drug Administration (FDA) approved enasidenib (Idhifa, Celgene/Agios) for adults with relapsed and refractory acute myelogenous leukemia (AML) with an IDH2 mutation. Enasidenib targets cells with mutant copies of isocitrate dehydrogenase-2 (IDH2), inhibiting the oncometabolite 2-hydroxyglutarte (2-HG) formed by the mutant IDH2. Areas covered: We review the studies leading to enasidenib's approval, as well as common side effects and safety issues experienced during the clinical trials. There is a focus on the diagnosis and treatment of these side effects including differentiation syndrome. Expert commentary: We are experiencing a revolution in the understanding of the mechanism of AML. A majority of the effort has been concentrated on targeting gene mutations or pathway activations with precision therapeutics. Enasidenib is beneficial in a patient population that previously had limited treatment options. However, given the fact that enasidenib is a highly specific inhibitor of an early stable mutation, it is questionable whether a strategy of targeting a single mutation or pathway in relapsed AML will allow for better than the 20% complete remission (CR) rate observed with this therapy. ...Continue Reading

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Citations

Dec 11, 2019·International Journal of Laboratory Hematology·Damodaran Narayanan, Olga K Weinberg
Sep 29, 2019·Expert Reviews in Molecular Medicine·Judith E Unterlass, Nicola J Curtin
Jun 2, 2020·Biomarker Research·Jifeng YuYongping Song
Apr 16, 2020·International Journal of Analytical Chemistry·Shuang-Long LiXiang-Jun Qiu
Apr 28, 2021·European Journal of Medicinal Chemistry·Xiaoxia LiangBo Jing
May 25, 2021·Blood Cancer Discovery·Dongqing YanMichael W Deininger
Jul 8, 2021·Cancer Discovery·Dongqing YanMichael W Deininger
Apr 3, 2019·Journal of Medicinal Chemistry·Andrew C FlickChristopher J O'Donnell

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