BACKGROUND: The understanding of T-cell lymphoma (TCL) pathobiology has grown substantially due to gene expression profiling and high-throughput next-generation sequencing (NGS). However, real-world data on mutational profiles of mature T-cell lymphomas (TCLs) are limited, and their impact on clinical decision making has not been reported. METHODS: A single-institution study of biopsies from patients with histopathologically confirmed T-cell lymphomas and available NGS data between January 1, 2021, to July 1, 2023, was performed. Reported variants were classified as disease-associated or pathogenic variants (DAV), or variants of unknown significance (VUS). Individual physicians were surveyed via email regarding the impact of NGS results on next steps in patient care. RESULTS: About 94% of patients (n = 93) had ≥ 1 variants identified
at least 1 pathogenic variant or likely pathogenic variant was identified in 71% of patients (n = 70). Variants were detected in 90 unique genes with 41% (37/90) having disease-associated variants (DAV). The genes with mutations most frequently resulting in disease-associated variants in this study were TET2, RHOA, DNMT3A and TP53, IDH2, and PLCG1. NGS results were integral to clinical management in 19% of patients per physician survey. CONCLUSION: This work gives insight into the real-world utility of NGS regarding clinical decision making for patients with T-cell lymphoma. Given the impact of NGS on prognostication, evaluation of therapeutic options, as well as cessation of potentially unhelpful treatments, these findings support the role of NGS as an important part in the management of T-cell lymphomas.