In the phase III LYM-3002 trial, patients with untreated stage II–IV mantle cell lymphoma were randomly assigned to receive either rituximab, cyclophosphamide, doxorubicin, bortezomib, and prednisone (VR-CAP) or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). In an 82-month follow-up analysis of 140 patients in the VR-CAP group and 128 patients in the R-CHOP group, median overall survival was significantly longer in the VR-CAP group (90.7 months versus 55.7 months; P = 0.001). The toxicity profile of both regimens was considered manageable: discontinuation owing to treatment-related adverse events (AEs) occurred in 8% of patients in the VR-CAP group and 6% of the R-CHOP group; 4% of patients in each group died owing to treatment-related AEs.