ASCO 2014: Bortezomib Combination Significantly Improves Progression-Free Survival in Newly Diagnosed Mantle Cell Lymphoma


Key Points

  • VR-CAP significantly prolonged progression-free survival in bone marrow transplant–ineligible newly diagnosed patients with mantle cell lymphoma compared to standard treatment.
  • The bortezomib-based regimen improved secondary endpoints including time to progression, time to subsequent treatment, and response rate.
  • VR-CAP was associated with additional but manageable toxicity.

An international, randomized phase III study found that replacing vincristine with bortezomib (Velcade) in R-CHOP (rituximab [Rituxan] plus cyclophosphamide, doxorubicin, vincristine, and prednisone) significantly improved outcomes in newly diagnosed patients with mantle cell lymphoma who were ineligible for bone marrow transplant treatment. The bortezomib-based combination (VR-CAP) demonstrated a 59% relative improvement in progression-free survival, reported investigators at the 2014 ASCO Annual Meeting in Chicago (Abstract 8500).

Study Details

The open-label, multicenter, prospective study evaluated the efficacy and safety of VR-CAP vs R-CHOP in 487 patients with treatment-naive stage II, III, or IV mantle cell lymphoma who were not candidates for bone marrow transplant. Patients were randomly assigned to receive six to eight 21-day cycles of R-CHOP (n = 244) or VR-CAP (n = 243). The trial’s primary endpoint was progression-free survival, and secondary endpoints included time to progression, time to subsequent antilymphoma treatment, overall survival, response rate, and safety.

The median age of patients was 66 years, 74% were male, and 74% had stage IV disease. Patients received a median of six cycles of treatment.

Primary and Secondary Outcomes

After a median follow-up of 40 months, the median progression-free survival in the VR-CAP arm was 24.7 months vs 14.4 months in the R-CHOP arm (hazard ratio [HR] = 0.63, P < .001). Median overall survival had not been reached at the time of follow-up, while a median overall survival of 56.3 months was observed in patients treated with R-CHOP (HR = 0.80, P = .173).

The bortezomib combination demonstrated improvements in median time to progression (30.5 vs 16.1 months; HR = 0.58, P < .001), median time to subsequent treatment (44.5 vs 24.8 months; HR = 0.50, P < .001), and complete response rate (53% vs 42%; P = .007).

VR-CAP was associated with additional but manageable toxicity compared to R-CHOP, consistent with the known side effects of bortezomib and the R-CAP combination. Serious adverse events were reported in 38% of patients receiving VR-CAP vs 30% of R-CHOP patients, and grade ≥ 3 adverse events were reported in 93% vs 85% of patients.

 “This is one of the largest studies ever conducted in newly diagnosed [mantle cell lymphoma]. The substantial improvement seen in progression-free survival and in secondary endpoints, including complete response, time to next therapy and time to progression with [VR-CAP] in newly diagnosed mantle cell lymphoma patients, expands our understanding of [bortezomib’s] contribution to patients with [mantle cell lymphoma],” said Franco Cavalli, MD, Director of the Oncology Institute of Southern Switzerland, who presented the study.

The study was sponsored by Millennium Pharmaceuticals and conducted by Johnson & Johnson Pharmaceutical Research & Development. For full disclosures of the study authors, view the study abstract at

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.