IDH Mutated AML: Beyond Enasidenib and Ivosidenib Monotherapy

Abstract

Introduction Mutations in the isocitrate dehydrogenase (IDH) genes, IDH1 or IDH2, occur in approximately 20% of patients with acute myeloid leukemia (AML) and promote leukemogenesis through a block in normal myeloid differentiation and through the production of the oncometabolite 2-hydroxyglutarate (2HG).1 Selective oral inhibitors of mutant IDH1 and IDH2, leading to restoration of normal myeloid differentiation and reduction of 2HG have been developed, and are now approved as single-agent therapy, based on clinical efficacy observed within the original first-in-human trials.