Millennium: The Takeda Oncology Company announced results from the primary analysis of an international, randomized phase 3 study that showed treatment with a Velcade (bortezomib)-based combination therapy demonstrated a 59 per cent relative improvement in the study’s primary endpoint of progression-free survival (24.7 vs. 14.4 months; Hazard Ratio among previously untreated patients with mantle cell lymphoma (MCL) compared to treatment with a standard therapy. These data were presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

After a median follow up of 40 months, median overall survival (OS), a key secondary endpoint, had not been reached for patients who received the Velcade-based therapy (Velcade, rituximab, cyclophosphamide, doxorubicin, and prednisone, while a median OS of 56.3 months was observed in patients treated with the standard regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone Overall, among patients receiving VcR-CAP compared to R-CHOP, serious adverse events (SAEs) were reported in 38 per cent vs. 30 per cent of patients, and grade =3 adverse events were reported in 93 per cent vs. 85 per cent of patients.

"This is one of the largest studies ever conducted in newly diagnosed MCL. The substantial improvement seen in progression-free survival and in secondary endpoints, including complete response, time to next therapy and time to progression with the Velcade-based regimen in newly diagnosed mantle cell lymphoma patients, expands our understanding of Velcade’s contribution to patients with MCL," said Franco Cavalli, managing director, director of the Oncology Institute of Southern Switzerland.

"The 59 per cent relative improvement in progression-free survival, along with the trend suggesting improved OS with the Velcade-based regimen, has the potential to represent a significant advance in the frontline treatment of mantle cell lymphoma for some patients," said Michael Vasconcelles, MD, Global Head, Takeda Oncology Therapeutic Area Unit. "Patients with relapsed MCL have benefited from access to Velcade therapy since 2006. We look forward to working with regulatory authorities to bring this new information to physicians and patients in the near future."

The open-label, multicenter, prospective study evaluated the efficacy and safety of VcR-CAP vs. R-CHOP in 487 patients with newly diagnosed Stage II, III or IV MCL who were ineligible or not considered for a bone marrow transplant. An Independent Radiology Review Committee (IRC) assessed the primary efficacy endpoint. Key secondary endpoints for patients receiving VcR-CAP vs. R-CHOP included: 30.5 vs. 16.1 months median time to progression (HR 0.58; P<0.001) 44.5 vs. 24.8 months median time to subsequent anti-lymphoma treatment (HR 0.50; P<0.001)
53 per cent vs. 42 per cent CR+CRu rate (P=0.007).

The estimated four-year survival rate, which was not a pre-specified endpoint, was 64.4 per cent in the Velcade-containing arm versus 53.9 per cent in the control arm. Another secondary endpoint, the overall response rate (complete response plus complete response with persistent imaging abnormalities of unknown significance plus partial response; i.e., CR+CRu+PR) was 92 per cent in the Velcade-containing arm compared to 90 per cent in the control arm (P=0.275).

VcR-CAP was associated with additional but manageable toxicity compared to R-CHOP, consistent with the known side effects of Velcade and the R-CAP combination. Safety results for patients receiving VcR-CAP vs. R-CHOP included: Similar rates of peripheral neuropathy between the Velcade-containing arm and the control arm in all-grade peripheral neuropathy, (30 per cent vs. 29 per cent); the rate of grade =3 peripheral neuropathy was significantly higher in the Velcade-containing arm (7.5 per cent vs. 4.1 per cent) 72 per cent vs. 19 per cent rate of all-grade thrombocytopenia, but no difference in bleeding events (6 per cent vs. 5 per cent) 88 per cent vs. 74 per cent rate of all-grade neutropenia; 60 per cent vs. 46 per cent rate of infection 14 per cent vs. 15 per cent rate grade =3 febrile neutropenia.

The abstract, titled "Randomised 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) ," was presented by Franco Cavalli, managing director, Oncology Institute of Southern Switzerland.

Velcade (bortezomib) is co-developed by Millennium/Takeda and Janssen Pharmaceutical Companies. Millennium is responsible for commercialisation of Velcade in the US Janssen Pharmaceutical Companies are responsible for commercialisation in Europe and the rest of the world. Takeda Pharmaceutical Company Limited and Janssen Pharmaceutical K.K. co-promote Velcade in Japan. Velcade is approved in the US and 53 additional countries for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior treatment. Velcade is also approved in more than 90 countries for the treatment of patients with multiple myeloma (MM) and has been used to treat more than 550,000 patients worldwide.

The front line MCL open-label, multicentre study was conducted by Johnson & Johnson Pharmaceutical research & development, L.L.C. (J&JPRD), as part of J&JPRD’s global co-development agreement with Millennium.

Velcade (bortezomib) is approved for the treatment of patients with multiple myeloma. Velcade is also approved for the treatment of patients with mantle cell lymphoma who have already received at least one prior treatment.

Patients should not receive Velcade if they are allergic to bortezomib, boron or mannitol. Velcade should not be administered intrathecally. Women should avoid becoming pregnant or breastfeeding while taking Velcade. Patients with diabetes may require close monitoring and adjustment of their medication.