Samples from patients with AML show high concordance in detection of mutations by NGS at local institutions vs central laboratories

Next-generation sequencing (NGS) to identify pathogenic mutations is an integral part of acute myeloid leukemia (AML) therapeutic decision-making. The concordance in identifying pathogenic mutations between different NGS platforms at different diagnostic laboratories has been studied in solid tumors but not in myeloid malignancies to date. To determine this inter-laboratory concordance, we collected a total of 194 AML bone marrow or peripheral blood samples from newly diagnosed AML patients enrolled in the Beat AML® Master Trial (BAMT) at two academic institutions. We analyzed the diagnostic AML samples for the detection of pathogenic myeloid mutations in eight genes (DNMT3A, FLT3, IDH1, IDH2, NPM1, TET2, TP53, and WT1) locally using the Hematologic Neoplasm Mutation Panel (50-gene myeloid indication filter) (Site 1) or the GeneTrails® Comprehensive Heme Panel (Site 2) at the two institutions and compared them to the central results from the diagnostic laboratory for the BAMT, Foundation Medicine, Inc. (FMI). The overall percent agreement was over 95% each in all eight genes, with almost perfect agreement (kappa>0.906) in all but WT1, which had substantial agreement (kappa=0.848) when controlling for site. The minimal discrepancies were due to reporting variants of unknown significance (VUS) for the WT1 and TP53 genes. These results indicate that the various NGS methods used to analyze AML patient samples enrolled in the BAMT show high concordance, a reassuring finding given the wide utilization of NGS for therapeutic decision-making in AML.