Expert review of clinical pharmacology
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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. ⋯ 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. The proper role for single mutation targeting in AML needs to be carefully considered.