Addition of Bortezomib to R-CHOP in Patients With DLBCL According to Molecular Subgroups: 5-Year Follow-up of the REMoDL-B Study

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In a 5-year analysis of the UK/Swiss phase III REMoDL-B trial reported in the Journal of Clinical Oncology, Davies et al found that the addition of bortezomib to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone; RB-CHOP) as initial treatment was associated with improved outcomes among patients with molecular high-grade and activated B-cell diffuse large B-cell lymphoma (DLBCL).      

Study Details

In the trial, 1,129 patients with DLBCL were randomly assigned to receive RB-CHOP or R-CHOP. Primary analysis at a median follow-up of 30 months found no effect on progression-free survival or overall survival with the addition of bortezomib. A total of 1,077 patients underwent gene-expression profiling; the current analysis involves 801 patients identified by profiling with activated B-cell (n = 249; 124 in RB-CHOP group vs 125 in R-CHOP group), germinal center B-cell (n = 469; 229 vs 240), or molecular high-grade lymphoma (n = 83; 41 vs 42).

Key Findings

At a median follow up of 64 months among the 801 patients, no significant benefit of RB-CHOP vs R-CHOP was observed for progression-free survival or overall survival. Hazard ratios (HRs) were 0.81 (P = .085) for 5-year progression-free survival and 0.86 (P = .32) for 5-year overall survival.

Among patients with activated B-cell lymphomas, 5-year progression-free survival was 69.4% in the RB-CHOP group vs 54.4% in the R-CHOP group (HR = 0.65, 95% confidence interval [CI] = 0.43–0.98, P = .041). Overall survival at 5 years was 80.4% vs 67.4% (HR = 0.58, 95% CI = 0.35–0.95, P =.032).

Among patients with molecular high-grade lymphomas, 5-year progression-free survival was 54.9% vs 29.3% (HR = 0.46, 95% CI = 0.26–0.84, P = .011) and 5-year overall survival was 60.0% vs 47.5% (HR = 0.62, 95% CI = 0.32–1.20, P = .16).

Among patients with germinal center B-cell lymphomas, 5-year progression-free survival was 73.3% vs 74.5% (HR = 1.05, 95% CI = 0.74–1.50, P = .77) and 5-year overall survival was 82.4% vs 85.0% (HR = 1.27, 95% CI = 0.81–1.98, P = .3).

The investigators concluded, “Patients with activated B-cell and molecular high-grade DLBCL may benefit from the addition of bortezomib to R-CHOP in initial therapy.”

Peter W.M. Johnson, MD, of the Centre for Cancer Immunology, Southampton General Hospital, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Janssen-Cilag, the National Institute for Healthcare Research, and Cancer Research UK. For full disclosures of the study authors, visit

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