The European Commission ( EU ) has approved a variation to the terms of the marketing authorisation of Velcade ( Bortezomib ) 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 blood stem-cell transplantation.
The approval of Velcade in mantle cell lymphoma is based on data from the phase 3 study, LYM-3002.
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.
LYM-3002 was a randomised, open-label, active-controlled, multicentre, international, prospective phase 3 study including 487 patients with newly diagnosed mantle cell lymphoma who were ineligible, or not considered, for bone marrow transplantation.
The results showed significant benefits when treating patients with mantle cell lymphoma using a Bortezomib-based combination ( VR-CAP ), compared to a widely used standard of care combination ( R-CHOP ) that did not include Bortezomib.
The VR-CAP regimen significantly improved progression-free survival ( PFS ), the primary endpoint, and showed improvements across a range of secondary endpoints.
An independent review committee reported the increase in progression-free survival to be 59% ( median 24.7 vs 14.4 months; hazard ratio, HR=0.63; p less than 0.001 ), whereas the study investigators reported the increase in progression-free survival to be 96% ( median 30.7 vs 16.1 months; HR=0.51; p less than 0.001 ).
VR-CAP was associated with additional, but manageable, toxicity when compared to R-CHOP. Overall, among patients receiving VR-CAP compared to R-CHOP, serious adverse events were reported in 38% vs 30% of patients and grade greater than or equal to 3 adverse reactions were reported in 93% vs 85%.
Discontinuations of treatment due to adverse reactions were 9% ( VR-CAP ) vs 7% ( R-CHOP ) and on-treatment drug-related deaths were 2% vs 3%.
Mantle cell lymphoma is considered to be a rare and aggressive type of blood cancer which can be challenging to treat and is associated with a poor prognosis.
Mantle cell lymphoma is characterised by small patient populations, impacting fewer than 0.45 in 100,000 people in Europe and with a median age at diagnosis of 65.
Mantle cell lymphoma is much more predominant in men than women and accounts for 6% of all non-Hodgkin's lymphomas.
Median overall survival is typically four to five years, and only one to two years in patients following the first relapse.
Mantle cell lymphoma typically involves the lymph nodes, but can spread to other tissues, such as the bone marrow, liver, spleen and gastrointestinal tract. ( Xagena )
Source: Janssen-Cilag, 2015