UC Davis

Introduction: Acute myeloid leukemia (AML) remains a disease with high mortality, especially for older patients and those with relapsed/refractory (R/R) disease. With recent advances in molecular testing, targeting particular leukemogenic mutations such as those occurring in isocitrate dehydrogenase (IDH) became possible. Enasidenib is a new small-molecule inhibitor of mutant isocitrate dehydrogenase-2 (IDH2). Aim: The objective of this article is to review the evidence for the use of enasidenib in R/R AML, as well as to outline future directions of enasidenib therapy. Evidence Review: Enasidenib was approved in August 2017, after a successful Phase I/II trial showing an overall response rate (ORR) of 40.3% in R/R disease, with 19.3% of patients achieving complete remission (CR). Enrollees in the trial were mostly older adults. The most prominent toxicities were hyperbilirubinemia and IDH-differentiation syndrome (IDH-DS), though the drug was generally well tolerated and the maximum tolerated dose was not reached. A Phase III trial is currently ongoing. Conclusion: Enasidenib provides a new therapeutic option for patients with R/R AML. Further studies are ongoing to ascertain its role in combination with other agents and newly diagnosed disease.