Enasidenib, a targeted inhibitor of mutant IDH2 proteins for treatment of relapsed or refractory acute myeloid leukemia.
Mutations in IDH2 genes (mIDH2) occur in approximately 12% of patients with acute myeloid leukemia. Enasidenib is an oral, small-molecule inhibitor of mIDH2 proteins. Enasidenib is shown to suppress the oncometabolite, 2-hydroxyglutarate, and promote differentiation of leukemic bone marrow blasts. In a Phase I dose-escalation and expansion study, 40.3% of patients with relapsed/refractory acute myeloid leukemia responded to enasidenib monotherapy, including 19.3% who achieved complete remission and 11% who proceeded to transplant. Median overall survival was 9.3 months. 2-hydroxyglutarate suppression did not predict response and mIDH2 clearance was possible, but not required for response. Patients with ≥6 co-mutations or NRAS co-mutations were less likely to attain a response. Enasidenib was safe and well tolerated with low rates of treatment-related adverse events. [Formula: see text].
['Stein|Eytan M|EM|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000631:Aminopyridines D001854:Bone Marrow Cells D002454:Cell Differentiation D018572:Disease-Free Survival D005260:Female D020558:GTP Phosphohydrolases D006801:Humans D007521:Isocitrate Dehydrogenase D015470:Leukemia, Myeloid, Acute D008297:Male D008565:Membrane Proteins D008875:Middle Aged D050505:Mutant Proteins D009154:Mutation D012008:Recurrence D014227:Triazines
enasidenib IDH2 relapsed refractory acute myeloid leukemia 2-hydroxyglutarate 2-HG AG-221 hematologic malignancy isocitrate dehydrogenase 2