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Critical evaluation of current molecular MRD strategies including NGS for the management of AML patients with multiple mutations

Current follow‐up procedures in patients with acute myeloid leukemia (AML) comprise cytomorphology, multiparameter flow cytometry (MFC), and molecular genetics by polymerase chain reaction (PCR)– based methods, Sanger, and, increasingly, next‐generation sequencing (NGS). Commercial myeloid NGS panels identify multiple mutations in most AML patients at diagnosis. Before NGS, follow‐up strategies using highly sensitive quantitative real‐time PCR (qPCR) were limited to a few reciprocal rearrangements or hotspot mutations such as NPM1. NGS offers follow‐up monitoring to virtually all AML patients, including clonal and subclonal changes. However, interpretation of NGS MRD results for individual patients remains challenging. Clinicians face uncertainty on how to proceed in patients with persisting mutation load by NGS, how to interpret divergent kinetics of various markers by NGS, and how to weigh the different sensitivities of NGS and qPCR.