Abstract
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 oftranslocations 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 inandwere associated with shorter overall survival (OS) only in younger patients. A higher proportion ofmutations 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.
Overview
- The study investigates the frequency of recurring gene mutations and their relation to well-known biomarkers in patients with diffuse large B-cell lymphoma (DLBCL) with refractory or relapsed disease compared to those with complete remission.
- The study uses cohorts of R-CHOP-like treated DLBCL enrolled in clinical trials of the Deutsche Stemzellen-Hauptversuch (DSHNHL) to identify biological risk factors associated with treatment response.
- The study aims to examine the differences in biomarker profiles between younger and elderly patients with refractory or relapsed DLBCL and to identify mutations associated with treatment response.
Comparative Analysis & Findings
- The biomarker profile of patients with refractory or relapsed DLBCL differed between younger and elderly patients, with a higher frequency of 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, and mutations inandwere associated with shorter overall survival (OS) only in younger patients.
- A higher proportion ofmutations was detected in female patients of the elderly DLBCL patient cohort, highlighting the striking differences in biomarker distribution between younger and elderly as well as female and male patients.
Implications and Future Directions
- The study highlights the importance of considering age and sex in the biomarker analysis of DLBCL patients with refractory or relapsed disease.
- Future studies should investigate the clinical implications of the identified biomarkers and develop targeted therapies for patients with refractory or relapsed DLBCL.
- The study emphasizes the need for further research into the biological mechanisms underlying the differences in biomarker profiles between younger and elderly patients and female and male patients with DLBCL.