ASH 2021 | The impact of IDH mutated clones in NPM1+ AML

Curtis Lachowiez, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses the results from a study investigating the clonal hierarchy of NPM1-mutated/IDH-mutated (NPM1+/IDH+) acute myeloid leukemia (AML), the predictive value of IDH mutations in NPM1+ AML, and the dynamics of IDH mutations during treatment using next-generation sequencing (NGS). In this study, 18% and 23% of patients with NPM1+ AML carried IDH1 and IDH2 mutations respectively, and IDH1+ was sub-clonal in 40% of cases. It was found that IDH1 and IDH2 mutations develop at different time points during leukemogenesis. Indeed, whilst IDH1+ was mostly sub-clonal and cleared in remission, IDH2+ often preceded NPM1 and persisted in remission. In addition, NPM1+/IDH+ was associated with improved overall survival (OS) and event-free survival (EFS) in patients receiving either standard intensive or venetoclax-based treatment regimens, especially in patients with IDH2 mutations. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.