Isocitrate Dehydrogenase 1 Mutation and Ivosidenib in Patients With Acute Myeloid Leukemia: A Comprehensive Review

Abstract

Acute myeloid leukemia (AML) arises from immature myeloid progenitors, resulting in a stem-cell-like proliferative state. This leads to excessive pools of immature cells that cannot function, which usually happens at the cost of the production of mature functional cells, leading to deleterious consequences. The management of AML has intensified as newer targeted therapies have come into existence owing to deeper genetic analysis of the disease and patients. Isocitrate dehydrogenase (IDH) is a cytosolic enzyme that is a part of the Krebs cycle and is extremely important in maintaining the homeostasis of the cell. It is produced by two different genes: IDH1 and IDH2. Ivosidenib has been associated with IDH1 inhibition and has been studied in numerous cancers. This review highlights the studies that have dealt with ivosidenib, an IDH1 inhibitor, in AML, the side effect profile, and the possible future course of the drug. After a scoping review of the available literature, we have identified that studies have consistently shown positive outcomes and that ivosidenib is a promising avenue for the management of AML. But it also has to be kept in mind that resistance to IDH inhibitors is on the rise, and the need to identify ways to circumvent this is to be addressed.

Active site remodeling in tumor-relevant IDH1 mutants drives distinct kinetic features and potential resistance mechanisms

“…Mutations at R132 drive >85% lower grade and secondary gliomas 6 and ~40% of cartilaginous tumors 7 , with R132H typically the most common 8,9 . These mutated enzymes have been successfully therapeutically targeted, with several FDA-approved allosteric selective inhibitors in use and more in clinical trials (recently reviewed in [10][11][12] ).…”