Enasidenib

Enasidenib is a targeted cancer therapy approved for adults with relapsed or refractory acute myeloid leukemia (AML) that harbor an IDH2 gene mutation. It is a selective, oral small‑molecule inhibitor of the mutant isocitrate dehydrogenase 2 (IDH2) enzyme. By inhibiting mutant IDH2, enasidenib lowers the level of the oncometabolite 2-hydroxyglutarate, which is associated with blocking cellular differentiation; inhibition of mutant IDH2 promotes differentiation of malignant myeloid cells.

Indications and usage

Enasidenib is indicated for the treatment of adults with relapsed or refractory AML with IDH2 mutation. It is used as monotherapy and is not restricted to patients who have received prior intensive chemotherapy. The therapy is intended for patients with susceptible IDH2 mutations as confirmed by diagnostic testing.

Administration and dosing

Enasidenib is taken orally, typically at a dose of 100 mg once daily, with or without food, and continued until disease progression or intolerable toxicity. Dose adjustments may be necessary for adverse events or organ impairment, and treatment should be managed by a clinician experienced in AML and targeted therapies.

Adverse effects and safety

Common adverse events include nausea, diarrhea, decreased appetite, fatigue, and edema, as well as cytopenias such as neutropenia and thrombocytopenia. A notable risk associated with IDH inhibitors is differentiation syndrome, which can be life‑threatening and requires prompt recognition and treatment, often with corticosteroids and supportive care. Regular monitoring of blood counts and metabolic parameters is recommended during therapy.

Clinical development

Evidence from phase I/II studies in IDH2-mutant AML demonstrated meaningful clinical activity in a subset of patients, supporting regulatory approval and ongoing evaluation of enasidenib in broader IDH2‑mutant hematologic malignancies.