Positive Data From Clinical Trials Of VELCADE
Millennium Pharmaceuticals announced positive data from clinical trials of VELCADE in newly diagnosed non-Hodgkin's lymphoma (NHL) patients.
These data showed that the addition of VELCADE to current standards of care produced high complete response (CR) rates in patients with newly diagnosed B-cell lymphoma (BCL) and mantle cell lymphoma (MCL).
"B-cell lymphoma is the most prevalent form of NHL, which affects approximately one million patients worldwide. Although current therapies are effective for some, a number of patients still do not achieve adequate response," said Nicolas Mounier, M.D., Ph.D., of Hopital Saint Louis. "This study shows that the addition of VELCADE to R-CHOP, the current standard of care, improved the complete response rate and overall survival compared to historical data. These data warrant moving forward in a randomized trial to show more definitively the additive benefit of VELCADE."
Efficacy and Toxicity of Two Schedules of R-CHOP Plus Bortezomib in Front- Line B Lymphoma Patients: A Randomized Phase II Trial from the Groupe d'Etude des Lymphomes de l'Adulte (Abstract #8010)
The Phase II study evaluated rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) plus VELCADE in newly diagnosed BCL patients. Results were presented by Dr. Mounier and showed:
-- Overall survival (OS) rate was 100 percent after a median follow-up of 12 months
-- Complete response and unconfirmed complete response (CR/CRu) rate was 83 percent, a superior result compared to the historical response for R-CHOP given for six cycles, without VELCADE, which ranged from 55 percent to 75 percent
-- Grade 3 and 4 toxicities included neurological toxicities, thrombocytopenia, leucopenia and infection
The trial included 48 evaluable patients. Patients received an average of six cycles of standard R-CHOP and were randomized between two schedules of VELCADE. Patients in arm A received VELCADE on days 1, 4, 8 and 11 and in arm B on days 1 and 8. For the first 24 patients in both arms, VELCADE was administered at 1 mg/m2 in arm A and 1.3 mg/m2 in arm B. For the next 24 patients, VELCADE was increased to 1.3 mg/m2 and 1.6 mg/m2, respectively.
Mantle Cell Lymphoma
"Mantle cell lymphoma remains one of the most challenging forms of lymphoma to treat. The data presented today suggest that VELCADE in combination with a current standard of care may improve the complete response rates, providing new hope for newly diagnosed mantle cell lymphoma patients," said Brad Kahl, M.D., Assistant Professor, University of Wisconsin. "As a result of these encouraging outcomes, the Eastern Cooperative Oncology Group has initiated a larger study to further evaluate the role of this VELCADE based therapy in these difficult-to-treat patients."
A Feasibility Study of VcR-CVAD with Maintenance Rituximab for Untreated Mantle Cell Lymphoma (Abstract #8062)
The Phase II pilot study evaluated VcR-CVAD (VELCADE, rituximab, cyclophosphamide, vincristine, doxorubicin, and dexamethasone) as initial therapy with rituximab consolidation and maintenance in newly diagnosed MCL patients. Results from the trial conducted by Dr. Kahl showed:
-- Overall response rate was 88 percent with 82 percent of patients achieving a CR/CRu
-- After 12 months follow-up, median OS and progression-free survival had not yet been reached
-- Grade 3 and 4 toxicities included peripheral neuropathy, thrombocytopenia and neutropenia
The encouraging response rates noted in this study provide the basis for the Eastern Cooperative Oncology Group protocol 1405, which will test the regimen with VELCADE 1.3 mg/m2 and vincristine 1.0 mg in a cooperative group setting.
The study included 17 evaluable patients. In the initial study design, patients received VELCADE at either 1.5 mg/m2 or 1.3 mg/m2 on days 1 and 4, rituximab 375 mg/m2 IV on day 1, cyclophosphamide 300 mg/m2 IV for three hours twice a day with six doses on days 1 through 3, doxorubicin 50 mg/m2 via continuous infusion over 48 hours on days 1 and 2, vincristine 2 mg IV on day 3 and dexamethasone 40 mg once a day on days 1 through 4. To manage the peripheral neuropathy, VELCADE and vincristine doses were reduced to 1.3 mg/m2 and 1 mg respectively. Patients received the regimen every 21 days for six cycles with Granulocyte Colony-Stimulating Factor (G-CSF) cytokine support.
About Non-Hodgkin's Lymphoma (NHL) and Mantle Cell Lymphoma (MCL)
NHL is the most common hematological cancer, the fifth leading cause of cancer death and the second fastest-growing form of cancer in the U.S. The prevalence of NHL in the U.S. is approximately 400,000 patients, including approximately 200,000 patients with diffuse large B-cell lymphoma, 100,000 patients with follicular and marginal zone lymphoma and 10,000 with MCL. There are approximately 54,000 new cases of NHL diagnosed in the U.S. per year, and 19,000 deaths are attributed to the disease annually.
MCL is an aggressive, rapidly progressive subtype of NHL and is not curable with standard treatment. The median life expectancy for a patient with MCL following first relapse is one to two years.
VELCADE is being co-developed by Millennium Pharmaceuticals, Inc. and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Millennium is responsible for commercialization of VELCADE in the U.S.; Janssen-Cilag is responsible for commercialization in Europe and the rest of the world. Janssen Pharmaceutical K.K. is responsible for commercialization in Japan. For a limited period of time, Millennium and Ortho Biotech Inc. will co-promote VELCADE in the U.S. VELCADE is approved in more than 80 countries worldwide.
In the U.S., VELCADE is indicated for the treatment of patients with multiple myeloma who have received at least one prior therapy. VELCADE is indicated for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy. VELCADE is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol. VELCADE should be administered under the supervision of a physician experienced in the use of antineoplastic therapy. In the European Union and many other countries worldwide, VELCADE is approved for patients with multiple myeloma after first relapse.
Risks associated with VELCADE therapy include new or worsening peripheral neuropathy, hypotension observed throughout therapy, cardiac and pulmonary disorders, gastrointestinal adverse events, thrombocytopenia, neutropenia and tumor lysis syndrome. Women of childbearing potential should avoid becoming pregnant while being treated with VELCADE. Cases of severe sensory and motor peripheral neuropathy have been reported. The long-term outcome of peripheral neuropathy has not been studied in mantle cell lymphoma. Acute development or exacerbation of congestive heart failure, and/or new onset of decreased left ventricular ejection fraction has been reported, including reports in patients with few or no risk factors for decreased left ventricular ejection fraction. There have been rare reports of acute diffuse infiltrative pulmonary disease of unknown etiology such as pneumonitis, interstitial pneumonia, lung infiltration and Acute Respiratory Distress Syndrome in patients receiving VELCADE. Some of these events have been fatal. A higher proportion of these events have been reported in Japan. There have been rare reports of RPLS in patients receiving VELCADE. RPLS is a rare, reversible, neurological disorder which can present with seizure, hypertension, headache, lethargy, confusion, blindness, and other visual and neurological disturbances. VELCADE is associated with thrombocytopenia and neutropenia. There have been reports of gastrointestinal and intracerebral hemorrhage in association with VELCADE. Transfusions may be considered. Complete blood counts (CBC) should be frequently monitored during treatment with VELCADE. Rare cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions.