Patients with diffuse large B cell lymphoma (DLBCL) who have activated B-cells and who are classified as having molecular high-grade disease may benefit from the addition of bortezomib to the initial therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), according to 5-year follow up data from the phase 3 REMoDL-B clinical trial, published in the Journal of Clinical Oncology.

“Ideally, this should be confirmed in a prospective trial, with a more potent proteasome inhibitor carrying less risk of additive neurotoxicity,” the researchers wrote.

Read more about the genetics of DLBCL

The trial compared the effect of R-CHOP to that of R-CHOP plus bortezomib in patients with DLBCL. At a median follow-up of 30 months, the researchers saw that the addition of bortezomib to the R-CHOP regimen had no effect on patients’ progression-free survival or overall survival. However, when they retrospectively analyzed the data using a gene expression-based classifier, they identified a molecular high-grade group of patients who had worse outcomes. 

In the present study, they present an updated analysis of the results based on the gene-expression-based classification of the patients as having activated B-cell lymphoma, germinal center B-cell lymphoma, or molecular high-grade lymphoma. 

At a median follow-up of 64 months, the researchers still did not find any benefits of bortezomib on progression-free and overall survival but when they specifically looked at patients with activated B-cell lymphoma, they found that overall survival was improved in the R-CHOP plus bortezomib group compared to the R-CHOP only group. 

Moreover, the 5-year progression-free survival was higher in patients with molecular high-grade lymphoma.

“This study confirms that different molecular subtypes of DLBCL exhibit different responses to bortezomib when given in combination with R-CHOP,” the researchers wrote.

DLBCL is the most common cancer of the lymphatic system, comprising around a third of non-Hodgkin lymphoma cases.


Davies AJ, Barrans S, Stanton, et al. Differential efficacy from the addition of bortezomib to R-CHOP in diffuse large B-cell lymphoma according to the molecular subgroup in the REMoDL-B study with a 5-year follow-up. J Clin Oncol. Published online March 27, 2023. doi:10.1200/JCO.23.00033

A randomised evaluation of molecular guided therapy for diffuse large B-cell lymphoma with bortezomib (REMoDL-B). US National Library of Medicine. Last updated April 15, 2016. Accessed April 4, 2023.