enasidenib + azacitidine

**Enasidenib + azacitidine** is a combination therapy used primarily in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) with mutations in isocitrate dehydrogenase 2 (IDH2). Enasidenib is an oral small-molecule inhibitor of mutant IDH2 enzymes that suppresses pathological production of 2-hydroxyglutarate (2-HG), leading to restoration of normal cellular differentiation. Azacitidine is a hypomethylating agent that inhibits DNA methyltransferases, resulting in reduced DNA methylation and reactivation of tumor suppressor gene expression. The combination demonstrates synergistic effects on reducing aberrant DNA methylation and enhancing leukemic cell differentiation[1][2][3][4][5][7]. This combination has shown improved response rates over monotherapy with either agent in clinical trials, particularly in patients with newly diagnosed or relapsed/refractory IDH2-mutant AML not eligible for intensive chemotherapy[2][3][5][7].