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. The proper role for single mutation targeting in AML needs to be 
carefully considered.