It has been announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending the approval of bortezomib (velcade) in combination with rituximab, cyclophosphamide, doxorubicin and prednisone, for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are unsuitable for haematopoietic stem cell transplantation.¹

MCL is a rare and aggressive type of blood cancer that can be challenging to treat and is associated with a poor prognosis.^{2, 3}

The positive opinion of the CHMP was based on data from the Phase III study, LYM-3002.

In the European Union (EU), bortezomib is currently indicated for the treatment of multiple myeloma (MM), another rare blood cancer, either as monotherapy or in combination with of other treatment regimens.⁴

Study Efficacy Results⁵

LYM-3002 was a randomised, open-label, active-controlled, multicentre, international, prospective Phase III study including 487 patients with newly diagnosed MCL who were ineligible, or not considered, for bone marrow transplantation.

The results showed significant benefits when treating newly diagnosed patients with MCL using a bortezomib-based combination,  compared to a widely used standard of care combination not including bortezomib.

The VR-CAP regimen significantly improved progression-free survival (PFS), the primary endpoint, and showed improvements across a range of secondary endpoints.⁵

An independent review committee reported the increase in PFS to be 59 percent (median 24.7 vs. 14.4 months; HR 0.63; p<0.001), whereas the study investigators reported the increase in PFS to be 96 percent (median 30.7 vs. 16.1 months; HR 0.51; p<0.001).⁵

Study Safety Results

VR-CAP was associated with additional, but manageable, toxicity when compared to VR-CHOP.⁵

Overall, among patients receiving VR-CAP compared to R-CHOP, serious adverse events (AE) were reported in 38 percent vs. 30 percent of patients and grade greater or equal to 3 were reported in 93 percent vs. 85 percent. Discontinuations of treatment due to AEs were nine percent (VR-CAP) vs. seven percent (R-CHOP) and on-treatment drug-related deaths were two percent vs. three percent.⁵

The CHMP's positive opinion will now be reviewed by the European Commission, which has the authority to grant a label extension for medicines in the European Economic Area.

A final decision on bortezomib use in MCL by the European Commission is anticipated early next year.

References

1. Summary of Opinion (post-authorisation). Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion/human/000539/WC500179316.pdf. Accessed December 2014

2. McKay P, Leach M, Jackson R, et al. Guidelines for the investigation and management of mantle cell lymphoma. Br J Haematol. 2012;159:405-26.

3. Williams ME, Dreyling M, Winter J, Muneer S, Leonard JP. Management of mantle cell lymphoma: key challenges and next steps. Clin Lymphoma Myeloma Leuk. 2010;10:336-46.

4. Velcade summary of product characteristics April 2014. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000539/WC500048471.pdf Last accessed November 2014.

5. Cavalli F, et al. Randomized Phase 3 study of rituximab, cyclophosphamide, doxorubicin, and prednisone plus vincristine (R-CHOP) or bortezomib (VR-CAP) in newly diagnosed Mantle Cell Lymphoma (MCL) patients (pts) ineligible for bone marrow transplantation (BMT). J Clin Oncol. 2014;32(5, Suppl.): abstract 8500.