Wednesday, October 04, 2023 LY17: Relapse Timing Is Associated With Distinct Evolutionary Dynamics in Diffuse Large B-Cell Lymphoma publication Hilton LK, Ngu HS, Collinge B, Dreval K, Ben-Neriah S, Rushton CK, Wong JCH, Cruz M, Roth A, Boyle M, Meissner B, Slack GW, Farinha P, Craig JW, Gerrie AS, Freeman CL, Villa D, Rodrigo JA, Song K, Crump M, Shepherd L, Hay AE, Kuruvilla J, Savage KJ, Kridel R, Karsan A, Marra MA, Sehn LH, Steidl C, Morin RD, Scott DW. Relapse Timing Is Associated With Distinct Evolutionary Dynamics in Diffuse Large B-Cell Lymphoma. Journal of Clinical Oncology 41: 4164-4177. 2023. https://ascopubs.org/doi/abs/10.1200/JCO.23.00570 PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is cured in more than 60% of patients, but outcomes remain poor for patients experiencing disease progression or relapse (refractory or relapsed DLBCL [rrDLBCL]), particularly if these events occur early. Although previous studies examining cohorts of rrDLBCL have identified features that are enriched at relapse, few have directly compared serial biopsies to uncover biological and evolutionary dynamics driving rrDLBCL. Here, we sought to confirm the relationship between relapse timing and outcomes after second-line (immuno)chemotherapy and determine the evolutionary dynamics that underpin that relationship. RESULTS: Outcomes to second-line therapy and ASCT are superior for late relapse (>2 years postdiagnosis) versus primary refractory (<9 months) or early relapse (9-24 months). Diagnostic and relapse biopsies were mostly concordant for cell-of-origin classification and genetics-based subgroup. Despite this concordance, the number of mutations exclusive to each biopsy increased with time since diagnosis, and late relapses shared few mutations with their diagnostic counterpart, demonstrating a branching evolution pattern. In patients with highly divergent tumors, many of the same genes acquired new mutations independently in each tumor, suggesting that the earliest mutations in a shared precursor cell constrain tumor evolution toward the same genetics-based subgroups at both diagnosis and relapse. For more information please visit the LY17 members trial page
