Next-generation sequencing for lymphoid neoplasms: Real-world utility from a clinical assay

Although next-generation sequencing (NGS) has become the standard of care in myeloid neoplasms, the utility of lymphoma NGS (LNGS) in the clinical setting has not been well established. The goal of this study was to document the real-world use of LNGS panels and assess their prognostic, predictive, and diagnostic value. A total of 384 cases were retrospectively reviewed in conjunction with pathology reports, including 121, 183, and 80 tested for the limited B-cell lymphoma panel (25 genes), expanded B-cell lymphoma panel (46 genes), or T-cell lymphoma panel (22 genes), respectively. Specimen types included 170 (44.3%) bone marrow, 120 (31.3%) peripheral blood, and 93 (24.2%) formalin-fixed paraffin-embedded tissue. 248/384 (64.6%) cases showed at least one mutation; 245/347 (70.6%) when excluding specimens known to be negative for lymphoma. Chronic lymphocytic leukemia/small lymphocytic lymphoma (SLL/CLL, 40.6%) and mantle cell lymphoma (MCL, 9.6%) were the most common lymphoma types tested. Mutations with prognostic value were found in 228/384 (59.4%) cases. 125 (32.6%) tests provided predictive value for response or resistance to a specific therapy. 36 tests (9.4%) provided diagnostic value, aiding the pathologist in classifying disease or rendering a more definitive diagnosis. LNGS results are most useful as being prognostic in CLL/SLL and MCL, diagnostic in angioimmunoblastic T-cell lymphoma and hairy cell leukemia, theranostic in lymphoplasmacytic lymphoma, and diagnostic and prognostic in follicular lymphoma and T/NK-cell large granular lymphocytic leukemia. Although clinical guidelines have not yet widely incorporated LNGS, when carefully designed and selectively ordered by clinicians and pathologists, the majority of tests do offer prognostic and predictive data which can aid in optimization of clinical management. The diagnostic value of LNGS testing is likely to increase with its further use and availability.