VELCADE(R) (bortezomib) for Injection Showed Positive Activity Across a Variety of Lymphomas
Monday June 13, 8:01 am ET
- Data affirms Company focus in non-Hodgkin's lymphoma, including mantle cell and indolent sub-types -
CAMBRIDGE, Mass., June 13 /PRNewswire-FirstCall/ -- Millennium Pharmaceuticals, Inc. (Nasdaq: MLNM - News) today announced VELCADE study results for the treatment of patients with indolent and mantle cell non-Hodgkin's lymphomas (NHL), and Waldenstom's Macroglobulemia at the 9th International Conference of Malignant Lymphoma in Lugano, Switzerland. Interim study results were reported from the multicenter, phase II trial of weekly versus twice- weekly dosing of VELCADE in combination with rituximab, in patients with indolent lymphomas. In these patients who were previously pretreated with chemotherapy and rituximab, response rates were similar in both arms (35 and 41 percent) and the safety profile improved with the weekly schedule.
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"We are very encouraged by the combination data results and given that many patients are still being treated and have not progressed, we could potentially see more responses," said Mansoor Saleh, M.D., of Georgia Cancer Specialists, Atlanta, GA., who presented the indolent lymphoma findings at the meeting. "We are especially excited about the weekly dosing schedule which combines added convenience and promising response rates with a well tolerated safety profile."
Data from a separate multicenter study, sponsored by the National Cancer Institute, directed by Memorial Sloan-Kettering Cancer Center and also presented at the meeting, indicated promising response rates and progression- free survival in follicular, marginal zone and mantle cell lymphomas with single agent VELCADE (56, 43 and 40 percent, respectively).
The U.S. Food and Drug Administration granted VELCADE fast track designation for relapsed and refractory mantle cell lymphoma (MCL). Favorable interim results from the phase II registration enabling study in MCL were also recently presented.(1) VELCADE has been approved in more than 50 countries worldwide and is currently indicated in the U.S. for the treatment of multiple myeloma (MM) patients who have received at least one prior therapy. Millennium and Johnson & Johnson Pharmaceutical Research and Development L.L.C. (J&JPRD) continue to investigate VELCADE globally in clinical trials in both hematologic and solid tumors.
The following is summary data from the clinical studies of VELCADE in lymphoma presented at Lugano:
Phase II Study of VELCADE® (bortezomib) for Injection Plus Rituximab in Indolent NHL
The randomized, multicenter phase II study led by Andre Goy, M.D., of Hackensack University Medical Center, Hackensack, NJ, assessed VELCADE in two separate study arms. Dosing schedules, weekly or twice-weekly, in combination with the standard weekly dose of rituximab in patients with relapsed or refractory indolent NHL were evaluated. The primary endpoint of the study is overall response rate (complete plus partial response). The first phase of the two-stage study was reported by Dr. Saleh. Results from 34 evaluable patients (17 in each arm) included:
* Overall response rates of 41 percent (7 out of 17) in the weekly arm and
35 percent (6 out of 17) in the twice-weekly arm;
* Complete or unconfirmed complete responses were observed in three
patients, two in the twice-weekly arm and one in the weekly arm;
* Additional responses may still be reported in ongoing patients in both
treatment arms;
* Approximately twice as many patients completed the 15-week duration of
therapy on the weekly arm compared to the twice-weekly arm and patients
in each arm received a similar median cumulative dose; and
* Both combination regimens were well tolerated and toxicities were
manageable. Adverse events included gastrointestinal symptoms, fatigue,
neutropenia and thrombocytopenia. One patient in the weekly arm and
seven patients in the twice-weekly arm experienced a grade 3 or 4 side
effect.
Phase II Studies in Single Agent VELCADE for Indolent and Mantle Cell Lymphomas
A multicenter phase II study led by Owen A. O'Connor, M.D., Ph.D., of Memorial Sloan Kettering Cancer Center, New York, NY, and sponsored by the National Cancer Institute, assessed single agent activity in relapsed or refractory indolent lymphomas, including follicular and marginal zone, and MCL. The study results from 65 evaluable patients included:
* A 56 percent overall response rate was observed in follicular lymphoma,
including one complete and one unconfirmed complete response;
* An overall response rate of 43 percent was achieved in marginal zone
lymphoma;
* Median event-free survival for all responding patients with indolent
lymphomas was 12.5 months compared to 12 months for the patients' prior
line of therapy;
* A 40 percent overall response rate was achieved in MCL, including three
complete and two unconfirmed complete responses;
* Median event-free survival for responding patients with MCL was 10
months compared to only 4.6 months for the patients' prior line of
therapy; and
* Adverse events observed were generally manageable and included
thrombocytopenia, lymphopenia, sensory neuropathy and rash.
"These results suggest that in patients with relapsed or refractory mantle cell or indolent lymphomas, VELCADE provides meaningful clinical activity with promising event-free survival where conventional chemotherapy has failed," said Dr. Owen A. O'Connor. "VELCADE as a single agent or in combination with conventional therapies in non-Hodgkin's lymphoma affords patients with these diseases new treatment opportunities."
A phase II clinical study of single agent VELCADE in patients with heavily pretreated relapsed, refractory lymphoma, including MCL and follicular lymphoma was led by Andrew Lister, M.D., and presented by Sandra Strauss, M.D., of St. Bartholomew's Hospital, London. Results for 48 evaluable patients included:
* Of the 24 MCL patients there was one complete response and six partial
responses with an overall response rate of 29 percent;
* Of the 11 follicular lymphoma patients there were two late responses
observed three months post-treatment resulting in an overall response
rate of 18 percent; and
* Adverse events were manageable and included thrombocytopenia, anemia,
fatigue, gastrointestinal symptoms and peripheral neuropathy.
A phase II clinical study of single agent VELCADE in patients with Waldenstom's Macroglobulemia, a form of indolent lymphoma, led by Steve Treon, M.D., Ph.D., of Dana Farber Cancer Institute, Boston, MA, assessed patients with relapsed or refractory disease and a median of two prior lines of therapy. Results from 25 evaluable patients included:
* A response rate which included minor and partial responses of 80
percent:
-- Partial response rate (greater than or equal to 50 percent decrease
in IgM) of 36 percent;
-- Minor response rate (greater than or equal to 25 percent decrease in
IgM) of 44 percent;
* Decreases in serum IgM observed in 24 out of 25 patients with a median
44 percent decrease; and
* Adverse events included neutropenia, leukopenia, gastrointestinal
symptoms and sensory neuropathy.
About Non-Hodgkin's Lymphoma
Non-Hodgkin's lymphoma (NHL) is the most common hematological cancer and the fifth leading cause of cancer death in U.S. There are approximately 56,400 new cases diagnosed per year, it is attributed to 19,200 deaths and is the second fastest growing form of cancer in the U.S.(2) The prevalence of NHL is approximately 400,000 patients, 77,000 patients with follicular lymphoma and approximately 10,000 with mantle cell lymphoma.(3,4) According to the American Cancer Society, the incidence of NHL has more than doubled since the 1970's. The average age of diagnosis is between 55 and 60.
About VELCADE® (bortezomib) for Injection
VELCADE is indicated for the treatment of multiple myeloma patients 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.
Risks associated with VELCADE therapy include new or worsening peripheral neuropathy, hypotension, cardiac disorders, gastrointestinal adverse events, thrombocytopenia and tumor lysis syndrome. Women of childbearing potential should avoid becoming pregnant while being treated with VELCADE.
In 331 patients who were treated with VELCADE in a phase III study, the most commonly reported adverse events were asthenic conditions (61%), diarrhea (57%), nausea (57%), constipation (42%), peripheral neuropathy (36%), vomiting (35%), pyrexia (35%), thrombocytopenia (35%), psychiatric disorders (35%), anorexia and appetite decreased (34%), parasthesia (27%), dysesthesia (27%), anemia and headache (26%), and cough (21%). Fourteen percent of patients reported at least one episode of grade 4 toxicity; the most common grade 4 toxicities were thrombocytopenia (4%), neutropenia (2%), and hypercalcemia (2%). A total of 144 patients on VELCADE (44%) reported serious adverse events (SAEs) during the study. The most commonly reported SAEs were pyrexia (6%), diarrhea (5%), dyspnea and pneumonia (4%), and vomiting (3%).
VELCADE is being co-developed by Millennium Pharmaceuticals, Inc. and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD). Millennium is responsible for commercialization of VELCADE in the U.S.; Ortho Biotech and Janssen-Cilag are responsible for commercialization in Europe and the rest of the world. Janssen Pharmaceutical K.K. is responsible for commercialization in Japan. VELCADE is approved in more than 50 countries worldwide, including the U.S., European Union and a number of countries within Latin America and South-East Asia. VELCADE also is approved in the European Union as a second-line treatment. It is indicated as a monotherapy for use in patients with progressive MM who have received at least one prior therapy and who have already undergone or are unsuitable for bone marrow transplantation. Millennium and J&JPRD continue to investigate VELCADE globally in phase I, II and III clinical trials in both hematologic and solid tumors, including front- line MM, non-Hodgkin's lymphoma and lung, prostate and ovarian cancers.
For more information about VELCADE clinical trials, patients and physicians can contact the Millennium Medical Product Information Department at 1-866-VELCADE (1-866-835-2233).
About Millennium
Millennium Pharmaceuticals, Inc., a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE, a novel cancer product, co- promotes INTEGRILIN® (eptifibatide) Injection, a market-leading cardiovascular product and has a robust clinical development pipeline of product candidates. The Company's research, development and commercialization activities are focused in three therapeutic areas: oncology, cardiovascular and inflammation. By applying its knowledge of the human genome, its understanding of disease mechanisms and its industrialized drug discovery platform, Millennium is seeking to develop breakthrough products. |
