Millennium: The Takeda Oncology Company with its parent company, Takeda Pharmaceutical Company, announced that the US Food and Drug Administration (US FDA) has approved Velcade (bortezomib) for injection for use in previously untreated patients with mantle cell lymphoma (MCL). Velcade is the first treatment in the United States to be approved for use in previously untreated patients with MCL. This approval extends the utility of Velcade beyond relapsed or refractory mantle cell lymphoma, for which it has been approved since 2006.

“Mantle cell lymphoma is a subtype of non-Hodgkin lymphoma that is usually a clinically aggressive malignancy, and it is a challenging disease to treat in part due to a relatively high risk of relapse,” said Andrew Evens, DO, MSc, director, Tufts Cancer Center; chief, division of hematology/oncology; director, Lymphoma Programme. “There are several new targeted drugs approved by the FDA for patients with relapsed or refractory disease, but up to this point, there had been none approved for the treatment of patients with previously untreated disease. Velcade, when used in the VcR-CAP regimen, Velcade, rituximab, cyclophosphamide, doxorubicin and prednisone, has demonstrated improved outcomes for patients, making it an important advance for the treatment of newly-diagnosed patients with mantle cell lymphoma.”

This approval is based on the results of an international, randomised, head-to-head phase 3 study that showed that previously untreated patients receiving a Velcade-containing combination (VcR-CAP) experienced a 59 per cent relative improvement in the study’s primary endpoint of progression-free survival (PFS) compared to those who were administered the standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) regimen (median 25 vs. 14 months; Hazard Ratio [HR] 0.63; P<0.001) at a median follow up of 40 months. An Independent Review Committee (IRC) assessed the primary efficacy endpoint of PFS. The complete response (CR) rate for patients receiving VcR-CAP vs. R-CHOP was 44 per cent vs. 34 per cent.

“We are delighted Velcade has received approval in previously untreated mantle cell lymphoma. The Velcade-combination delivered an 11-month median advantage in progression-free survival as compared to a current standard of care," said Dixie-Lee Esseltine, MD, FRCPC, vice president, oncology clinical research, Takeda Pharmaceuticals International Co. "Since 2006, Velcade has proven to be an important therapy for the treatment of relapsed or refractory mantle cell lymphoma, and it can now be used as an initial treatment for all patients with mantle cell lymphoma.”

The open-label, multicentre, prospective study evaluated the efficacy and safety of VcR-CAP vs. R-CHOP in 487 patients with previously untreated MCL who were ineligible or not considered for a bone marrow transplant. Velcade (1.3 mg/m2) is administered intravenously in combination with intravenous rituximab, cyclophosphamide, doxorubicin and oral prednisone (VcR-CAP) for six 3-week treatment cycles. Velcade is administered first followed by rituximab. Velcade is administered twice weekly for two weeks (days 1, 4, 8 and 11) followed by a 10-day rest period on days 12-21. For patients with a response first documented at cycle 6, two additional VcR-CAP cycles are recommended. At least 72 hours should elapse between consecutive doses of Velcade.

The most common adverse reactions occurring in =20 per cent of patients receiving the VcR-CAP regimen were neutropenia, leukopenia, anaemia, thrombocytopenia, lymphopenia, peripheral neuropathy, pyrexia, nausea and diarrhoea. Infections were reported for 31 per cent of patients in the VcR-CAP arm and 23 per cent of the patients in the R-CHOP arm including pneumonia (8 per cent versus 5 per cent). Adverse reactions leading to discontinuation occurred in 8 per cent of patients in the VcR-CAP arm and 6 per cent of patients in the R-CHOP arm. In the VcR-CAP group, the most commonly reported adverse reaction leading to discontinuation was peripheral sensory neuropathy (1 per cent; 3 patients).

MCL is a rare, aggressive type of B-cell non-Hodgkin lymphoma (NHL) that usually occurs in older adults. MCL constitutes about 6 per cent of cases of NHL. The disease typically begins in the lymph nodes but can spread to other tissues, such as bone marrow and liver. The expected overall survival for MCL is approximately four to five years, and the five-year survival rate for advanced stage MCL is approximately 50 per cent.

Velcade (bortezomib) is co-developed by Millennium/Takeda and Janssen Pharmaceutical Companies. Millennium is responsible for commercialization of Velcade in the US; Janssen Pharmaceutical Companies are responsible for commercialization 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 for the treatment of mantle cell lymphoma (MCL) as well as in 53 additional countries for the treatment of patients with 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.