Potential Benefit of Bortezomib Plus R-CHOP Treatment for Patients With Activated B-Cell and Molecular High-Grade Subtype DLBCL

Results from the Phase 3 REMoDL-B Trial

According to an updated analysis from the phase 3 REMoDL-B trial analyzing patients with diffuse large B-cell lymphoma (DLBCL) classified by gene expression profile, patients with activated B-cell (ABC) and molecular high-grade (MHG) subtypes may benefit from the addition of bortezomib, a proteasome inhibitor, to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in initial therapy.

According to Andrew J. Davies, MD, University of Southampton, Southampton, United Kingdom, and coauthors, “Molecular heterogeneity is a recognized feature of diffuse large B-cell lymphoma, with varying outcomes among karyotypic, genomic, and transcriptomic subtypes. Clinical trials have tested whether additional targeted therapies might improve outcomes, by modulating aberrant intracellular pathways in malignant B cells.”

In this trial, the study investigators compared R-CHOP with R-CHOP + bortezomib (RB-CHOP) in patients with DLBCL, stratified by molecular subtype. 1,077 patients were enrolled in this study, with 801 identified with the ABC, MHG, or Germinal Center B-Cell subtype. Eligible patients were older than 18 years with untreated DLBCL, as well as healthy enough for full-dose chemotherapy, as well as having adequate biopsies for classification by gene expression profile

The primary analysis at a median follow-up of 30 months found no effect of bortezomib on progression-free survival (PFS) or overall survival (OS). At a median follow-up of 64 months, there was no overall benefit of bortezomib on PFS or OS (5-year PFS hazard ratio [HR], .81; P = .085; OS HR, .86; P = .32). 

However, improved PFS and OS were seen in ABC lymphomas after RB-CHOP. Notably, the 5-year OS was 67% with R-CHOP versus 80% with RB-CHOP (HR, 0.58; 95% confidence interval [CI], .35 to .95; P = .032). The 5-year PFS was also higher in MHG lymphomas: 29% with R-CHOP vs 55% with RB-CHOP (HR, 0.46; 95% CI, .26 to .84.)

In terms of safety, adverse events occurring in this trial were comparable to those reported previously, and the addition of bortezomib was well-tolerated.

Dr Davies et al concluded, “Patients with ABC and MHG DLBCL may benefit from the addition of bortezomib to R-CHOP in initial therapy.”

Source: 

Davies AJ, Barrans S, Stanton L, 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 [published online ahead of print, 2023 Mar 27]. J Clin Oncol. 2023;JCO2300033. doi:10.1200/JCO.23.00033