ASCO 2014: Bortezomib Combination Significantly Improves Progression-Free Survival in Newly Diagnosed Mantle Cell Lymphoma
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 abstract.asco.org.
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®.
