Age- and gender-specific molecular characteristics of diffuse large B-cell lymphoma: Results from clinical trials of the DSHNHL/GLA.

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. Despite a high cure rate, too many patients show refractory (ref) or relapsed (rel) disease. This study examines the frequency of recurring gene mutations and their interplay with well-known biomarkers in female and male patients between 18 and 80 years with ref/rel DLBCL compared to patients with complete remission (CR) to identify biological risk factors associated with treatment response, using cohorts of R-CHOP-like treated DLBCL enrolled in clinical trials of the DSHNHL. The biomarker profile of patients differed between younger and elderly patients with ref/rel DLBCL, with a higher frequency of BCL2 translocations in younger patients, and higher numbers of ABC subtypes and MYC protein expression in the elderly. Amplicon sequencing revealed generally higher mutation frequencies in the younger cohort. Mutations in CREBBP and TNFRSF14 were associated with shorter overall survival (OS) only in younger patients. A higher proportion of GNA13 mutations was detected in female patients of the elderly DLBCL patient cohort, clearly emphasizing the striking differences in biomarker distribution between younger and elderly as well as female and male patients.