Robak T, et al. - In transplant-ineligible patients with untreated, newly diagnosed, mantle cell lymphoma, the efficacy and safety of frontline bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) vs rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were compared in the LYM-3002 study. Researchers analyzed the final overall survival and safety outcomes for patients in the long-term follow-up phase after the primary progression-free-survival endpoint was met. Significantly longer survival, and a manageable and expected safety profile was demonstrated by VR-CAP vs R-CHOP. Further evaluation of VR-CAP in patients with previously untreated mantle cell lymphoma was supported.

Methods

• At 128 clinical centres in 28 countries in Asia, Europe, North America, and South America, a randomised, open-label, phase 3 study, the LYM-3002, was performed.
• Participants were adult patients with confirmed stage II–IV previously untreated mantle cell lymphoma, Eastern Cooperative Oncology Group performance status score of 2 or less, who were ineligible for bone marrow transplantation.
• Six or eight 21-day cycles of VR-CAP (intravenous rituximab 375 mg/m², cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², and bortezomib 1·3 mg/m², plus oral prednisone 100 mg/m²) or R-CHOP (intravenous vincristine 1·4 mg/m² [2 mg maximum], rituximab 375 mg/m², cyclophosphamide 750 mg/m², and doxorubicin 50 mg/m², plus oral prednisone 100 mg/m²) was randomly (1:1) administered to the participants.
• Using a computer-generated randomisation schedule prepared by the sponsor, randomisation was done; permuted blocks central randomisation was used (block size of 4).
• Randomisation was stratified by International Prognostic Index score and disease stage at diagnosis.
• Overall survival, which was analysed in the intention-to-treat population, was the primary endpoint of this final analysis.

Results

• Enrollment and random assignment of 487 patients was carried out between May 22, 2008, and Dec 5, 2011.
• The follow-up analysis included 268 patients (140 in the VR-CAP group and 128 in the R-CHOP group) with data available after the primary analysis clinical cutoff date of Dec 2, 2013.
• A significantly longer median overall survival was observed in the VR-CAP group vs in the R-CHOP group (90·7 months [95% CI 71·4 to not estimable] vs 55·7 months [47·2 to 68·9]; hazard ratio 0·66 [95% CI 0·51–0·85]; p=0·001) after median follow-up of 82·0 months (IQR 74·1–94·2).
• Since the primary analysis cutoff, three new adverse events were reported (one each of grade 4 lung adenocarcinoma and grade 4 gastric cancer in the VR-CAP group, and one case of grade 2 pneumonia in the R-CHOP group).
• Findings revealed death of 103 (42%) of 243 patients in the VR-CAP group, and 138 (57%) of 244 in the R-CHOP group; progressive disease was identified as the most common cause of death.