In patients with diffuse large B-cell lymphoma (DLBCL), late relapses are commonly characterized by genetically distinct and chemotherapy-naïve disease, according to research published in the Journal of Clinical Oncology. The findings suggest immunochemotherapy-based regimens may remain a rational treatment option in this patient population.
Researchers evaluated the relationship between relapse timing and outcomes after second-line immunochemotherapy and the evolutionary dynamics underpinning that relationship in refractory or relapsed DLBCL.
The team examined outcomes in a large population-based cohort of 221 patients with DLBCL who experienced progression or relapse after first-line treatment and were treated with second-line immunochemotherapy with an intention-to-treat with autologous stem-cell transplantation (ASCT). They also compared serial DLBCL biopsies from 129 patients who underwent molecular characterization, including whole-genome or whole-exome sequencing (n=73).
The study demonstrated superior outcomes to second-line therapy and ASCT among patients with late relapse (>2 years postdiagnosis) compared with those with primary refractory (<9 months) or early relapse (9-24 months).
Comparison of diagnostic and relapse biopsies revealed patterns of tumor evolution that were strongly correlated with the timing of DLBCL progression or relapse. The study found that the number of mutations exclusive to each biopsy increased with time since diagnosis and that biopsies from late relapses shared few mutations with the diagnostic biopsy.
In patients with highly divergent tumors, the analysis showed that many of the same genes acquired new mutations independently in each tumor. For example, BTG1, PIM1, and ETV6 each acquired mutations in an MCD-classified early relapse tumor pair. The researchers suggest, “The earliest mutations in a shared precursor cell constrain tumor evolution toward the same genetics-based subgroups at both diagnosis and relapse.”
“When precision medicine approaches are being considered, molecular characterization of the tumor at relapse is recommended as mutations and specific pathway perturbations may differ from those observed at the time of diagnosis,” the researchers wrote in their report.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures.
Hilton LK, Ngu HS, Collinge B, et al. Relapse timing is associated with distinct evolutionary dynamics in diffuse large B-Cell lymphoma. J Clin Oncol. Published online June 15, 2023. doi:10.1200/JCO.23.00570