Diminishing oncometabolic havoc: Approved IDH1 and IDH2 inhibitors in relapsed or refractory acute myeloid leukemia

Activating somatic mutations in isocitrate dehydrogenase (IDH) isoforms 1 and 2 in acute myeloid leukemia (AML) have been shown to contribute in wreaking intracellular oncometabolic havoc that adversely affects cellular growth and differentiation. Novel developments in IDH1 and IDH2 inhibitors have led to the recent U.S. Food and Drug Administration (FDA) approvals of these targeted agents in relapsed or refractory AML harboring these respective driver mutations. Their promising efficacy and well-tolerated toxicity profiles render them welcomed additions in the treatment landscape of AML. However, the IDH1 and IDH2 inhibitors ivosidenib and enasidenib, respectively, have unique class-effect toxicities that warrant early recognition in order for prompt management and re-institution of an otherwise effective class of agents.