The randomised evaluation of molecular-guided therapy for diffuse large B-cell lymphoma with bortezomib (REMoDL-B) trial has found no evidence that adding bortezomib to standard therapy improves outcomes in patients with diffuse germinal centre or activated B cell lymphoma.
For the study, published in the Lancet Oncology, participants were recruited from 107 cancer centres in the United Kingdom (n=94) and Switzerland (n=13).
Patients initially received one 21-day cycle of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) intravenously on day 1, and oral prednisolone on days 1-5. During this time, gene-expression profiling was carried out. Patients were then randomly assigned to continue R-CHOP alone or with bortezomib (RB-CHOP) on days 1 and 8 for cycles two to six.
At a median follow-up of 29.7 months, there was no evidence for a difference in 30-month progression-free survival (PFS) in the combined germinal centre and activated B-cell population between R-CHOP and RB-CHOP (70.1% vs 74.3%; HR, 0.86; 95% CI, 0.65-1.13; P=.28).
The most common grade ≥3 adverse event was haematological toxicity, reported in 39.8 per cent of patients given R-CHOP and 42.1 per cent of those given RB-CHOP.
Grade 3 or worse neuropathy occurred in 3.8 per cent patients given RB-CHOP versus 1.8 per cent given R-CHOP. Serious adverse events occurred in 42.5 per cent patients given R-CHOP and 50.2 per cent given RB-CHOP. There were five treatment-related deaths with R-CHOP and four with RB-CHOP.
Although the trial did not show any PFS benefit with the addition of bortezomib, it does show the feasibility of molecular phenotyping in a large multicentre study of rapidly progressive tumours and shown that the addition of bortezomib does not affect treatment outcomes in most patients with diffuse large B-cell lymphoma.