European Commission approves additional indication for VELCADE® (bortezomib) in mantle cell lymphoma

The decision from the European Commission follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) on 18 December 2014.¹ This approval allows for the marketing of VELCADE for the above indication in all 28 countries of the European Union (EU). The approval of VELCADE in MCL is based on data from the Phase 3 study, LYM-3002.²

In the European Union, VELCADE is currently indicated for the treatment of multiple myeloma (MM), another rare blood-based cancer, either as monotherapy or in combination with other treatment regimens.³

MCL is considered a rare and aggressive type of blood cancer which can be challenging to treat and is associated with a poor prognosis.^4,5

“We are delighted that the European Commission has approved extending the indications for use of VELCADE to include first-line therapy for patients with mantle cell lymphoma. We already offer IMBRUVICA as a second-line treatment in MCL and are pleased to be able to provide additional treatment options for this disease to patients and physicians,” said Thomas Stark, Vice President, Medical Affairs, Janssen Europe, Middle East and Africa (EMEA).

Study Efficacy Results

LYM-3002 was a randomised, open-label, active-controlled, multicentre, international, prospective Phase 3 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 patients with MCL using a VELCADE-based combination (VR-CAP^*), compared to a widely used standard of care combination (R-CHOP^†) that did not include VELCADE.² The VR-CAP regimen significantly improved progression-free survival (PFS), the primary endpoint, and showed improvements across a range of secondary endpoints.² 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).²

Study Safety Results

VR-CAP was associated with additional, but manageable, toxicity when compared to R-CHOP.² 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 ≥3 AEs 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.²

^*VELCADE, rituximab, cyclophosphamide, doxorubicin and prednisone (VR-CAP)
^† Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP)

References

1. European Medicines Agency. Committee for Medicinal Products for Human Use: Summary of opinion (post authorisation). Available at: http://www.ema.europa.eu/docs/en_GB/document_library/
   Summary_of_opinion/human/000539/WC500179316.pdf. Last accessed January 2015.
2. Cavalli F, Rooney B, Pei L, 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.
3. VELCADE EPAR summary for the public February 2014. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/000539/WC500048136.pdf. Last accessed January 2015.
4. 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.
5. Williams ME, Dreyling M, Winter J, et al. Management of mantle cell lymphoma: key challenges and next steps. Clin Lymphoma Myeloma Leuk. 2010;10:336-46.