enasidenib + venetoclax

The combination of **enasidenib** and **venetoclax** is an investigational, oral, small molecule combination therapy for the treatment of **IDH2-mutant acute myeloid leukemia (AML)**. - **Enasidenib** is an inhibitor of mutant isocitrate dehydrogenase 2 (**IDH2**) enzymes, which are frequently mutated in AML. It reduces levels of the oncogenic metabolite 2-hydroxyglutarate (2-HG), leading to differentiated cell death of leukemic cells. - **Venetoclax** is a selective inhibitor of the anti-apoptotic protein B-cell lymphoma 2 (**BCL-2**), leading to apoptosis in tumor cells dependent on BCL-2 for survival. Preclinical and early clinical evidence shows that this combination therapy may have **enhanced efficacy** over monotherapies in **IDH2-mutated AML**, especially relapsed/refractory (R/R) disease, without evidence of antagonism. Oral administration is the primary route. The combination may be effective with or without cytotoxic chemotherapy or hypomethylating agents, but is most specifically studied as a two-drug regimen in IDH2-mutant AML[1][7][8].