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Biopharmaceuticals Oncology

 News Release - December 7, 2009

VELCADE(R) (Bortezomib) for Injection Based Combinations Deliver Two-Year Overall Survival Rates of Up to 88 Percent in Patients with Previously Untreated Multiple Myeloma

Data presented at plenary session show VELCADE based maintenance combinations nearly double complete remission rates from 23 to 42 percent

NEW ORLEANS--(HSMN NewsFeed)--Millennium: The Takeda Oncology Company today reported the presentation of results from a double randomized Phase III clinical trial of VELCADE based combinations for the treatment of patients with previously untreated multiple myeloma (MM). The VELCADE based combinations evaluated in the study demonstrated two-year overall survival rates ranging between 81 and 88 percent. The results showed a notable increase in the rate of complete remissions (CR), which nearly doubled from 23 percent after six cycles of induction to 42 percent after VELCADE based maintenance treatment. The rigor of double randomization isolates the impact of VELCADE based maintenance therapy, independent of the induction regimen. These cooperative group data were generated by the Spanish Myeloma Group PETHEMA/GEM and presented by Maria-Victoria Mateos, M.D., Ph.D., Hospital Universitario de Salamanca, Salamanca, Spain. This presentation was selected for the distinguished plenary session at the 51st Annual Meeting of the American Society of Hematology (ASH), held December 5-8, 2009 in New Orleans, Louisiana.

“In this study, VELCADE based combinations delivered impressive two-year survival rates of up to 88 percent and showed that maintenance regimens with VELCADE can further improve on the efficacy of VELCADE based induction therapy after an initial treatment phase of 31 weeks,” said Dr. Mateos.

“Prolonging overall survival is the primary goal of therapy. We are extremely pleased by the depth of complete response, the increased efficacy seen with VELCADE based maintenance, and the impressive overall survival rates demonstrated in this study,” said Nancy Simonian, M.D., Chief Medical Officer, Millennium.

A Prospective, Multicenter, Randomized, Trial of Bortezomib/Melphalan/Prednisone (VMP) Versus Bortezomib/Thalidomide/Prednisone (VTP) as Induction Therapy Followed by Maintenance Treatment with Bortezomib/Thalidomide (VT) Versus Bortezomib/Prednisone (VP) in Elderly Untreated Patients with Multiple Myeloma Older Than 65 Years (Abstract #3)

This Phase III trial in 260 elderly patients with a median age of 73 years was conducted by the Spanish Myeloma Group PETHEMA/GEM. One third of the patients were over the age of 75. The updated results, which were presented by Dr. Mateos, showed:

  • After induction, the CR rate for all patients was 23 percent; after maintenance the CR rate was 42 percent.
  • At two years, the overall survival (OS) rate was 88 percent in both the VMP induction/ VT maintenance and VMP induction/VP maintenance arms; 84 percent in the VTP induction/VT maintenance arm; and 81 percent in the VTP induction/VP maintenance arm.
  • The projected three-year rate of overall survival for all patients in the trial was 75 percent.
  • Patients with cytogenetic abnormalities achieved a similar OS rate as those without cytogenetic abnormalities.
  • In the induction phase, 39 percent of patients in the VMP arm and 22 percent of patients in the VTP arm experienced neutropenia of grade 3 or higher; 5 percent of patients in the VMP arm and 9 percent of patients in the VTP arm experienced peripheral neuropathy of grade 3 or higher; no patients in the VMP arm and 8 percent of patients in the VTP arm experienced cardiologic events of grade 3 or higher.
  • In the maintenance phase, 1 percent of patients in the VP arm and 3 percent of patients in the VT arm experienced neutropenia of grade 1 or grade 2; 2 percent of patients in the VP arm and 5 percent of patients in the VT arm experienced peripheral neuropathy of grade 3 or higher; and 1 percent of patients in the VP arm and 2 percent of patients in the VT arm experienced cardiologic events of grade 3 or higher.
  • Median progression free survival (PFS) with VT maintenance has not been reached; the median PFS with VP maintenance was reported to be 23 months (hazard ratio 1.7 and p=0.05).
  • OS in both the VT and VP arms were similar at a median follow up of 15 months (hazard ratio 1.1 and p=0.7).

Patients were randomized to receive 6 cycles of VMP or VTP as induction therapy followed by randomization to maintenance with VT or VP for up to three years. In the VMP arm patients received VELCADE 1.3 mg/m2 twice weekly for one 6-week cycle, followed by once weekly for five 5-week cycles in combination with oral melphalan 9 mg/m2 and prednisone 60 mg/m2 once daily on days 1 through 4 of each cycle. In the VTP arm patients received the same dose and schedule of VELCADE and prednisone, but instead of melphalan, they received thalidomide at a dose of 100 mg daily. Following the six cycles of induction, patients were randomized to maintenance with VELCADE at 1.3 mg/m2 on days 1, 4, 8 and 11 every three months in combination with either continuous thalidomide, 50 mg daily or prednisone, 50 mg on alternate days.

About Multiple Myeloma

Multiple myeloma is the second most common hematologic malignancy. In the U.S., more than 50,000 individuals have MM and 20,000 new cases are diagnosed each year. Worldwide there are approximately 74,000 new cases and over 45,000 deaths annually.


VELCADE is co-developed by Millennium Pharmaceuticals, Inc. and Ortho Biotech Oncology Research & Development, a unit of Johnson & Johnson Pharmaceutical Research & Development, L.L.C., and approved worldwide. 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. VELCADE is currently approved in more than 87 countries worldwide.

Important Safety Information

In the U.S., VELCADE is indicated for the treatment of patients with multiple myeloma. VELCADE also 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.

Risks associated with VELCADE therapy include new or worsening peripheral neuropathy, hypotension throughout therapy, cardiac and pulmonary disorders, reversible posterior leukoencephalopathy syndrome, gastrointestinal adverse events, thrombocytopenia, neutropenia, tumor lysis syndrome and hepatic events. Women of childbearing potential should avoid becoming pregnant while being treated with VELCADE. Nursing mothers are advised not to breastfeed while receiving 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 new onset of decreased left ventricular ejection fraction has been reported, including reports in patients with no risk factors for decreased left ventricular ejection fraction. There have been 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. There have been reports of Reversible Posterior Leukoencephalopathy Syndrome (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. Cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions. Patients who are concomitantly receiving VELCADE and drugs that are inhibitors or inducers of cytochrome P450 3A4 should be closely monitored for either toxicities or reduced efficacy. Patients on oral antidiabetic medication while receiving VELCADE should check blood sugar levels frequently.

Adverse Reaction Data

Safety data from Phase II and III studies of single-agent VELCADE 1.3 mg/m2/dose twice weekly for 2 weeks followed by a 10-day rest period in 1163 patients with previously treated multiple myeloma (N=1008, not including the Phase III, VELCADE plus DOXIL® [doxorubicin HCl liposome injection] study) and previously treated mantle cell lymphoma (N=155) were integrated and tabulated. In these studies, the safety profile of VELCADE was similar in patients with multiple myeloma and mantle cell lymphoma.

In the integrated analysis, the most commonly reported adverse events were asthenic conditions (including fatigue, malaise and weakness) (64%), nausea (55%), diarrhea (52%), constipation (41%), peripheral neuropathy NEC (including peripheral sensory neuropathy and peripheral neuropathy aggravated) (39%), thrombocytopenia and appetite decreased (including anorexia) (each 36%), pyrexia (34%), vomiting (33%), anemia (29%), edema (23%), headache, paresthesia and dysesthesia and headache (each 22%), dyspnea (21%), cough and insomnia (each 20%), rash (18%), arthralgia (17%), neutropenia and dizziness (excluding vertigo) (each 17%), pain in limb and abdominal pain (each 15%), bone pain (14%), back pain and hypotension (each 13%), herpes zoster, nasopharyngitis, upper respiratory tract infection, myalgia and pneumonia (each 12%), muscle cramps (11%), and dehydration and anxiety (each 10%). Twenty percent (20%) of patients experienced at least 1 episode of =Grade 4 toxicity, most commonly thrombocytopenia (5%) and neutropenia (3%). A total of 50% of patients experienced serious adverse events (SAEs) during the studies. The most commonly reported SAEs included pneumonia (7%), pyrexia (6%), diarrhea (5%), vomiting (4%), and nausea, dehydration, dyspnea and thrombocytopenia (each 3%).

In the Phase 3 VELCADE + melphalan and prednisone study, the safety profile of VELCADE in combination with melphalan/prednisone is consistent with the known safety profiles of both VELCADE and melphalan/prednisone. The most commonly reported adverse events for VELCADE in combination with MP vs MP, respectively, were thrombocytopenia (52% vs 47%), neutropenia (49% vs 46%), nausea (48% vs 28%), peripheral neuropathy (47% vs 5%), diarrhea (46% vs 17%), anemia (43% vs 55%), constipation (37% vs 16%), neuralgia (36% vs 1%), leukopenia (33% vs 30%), vomiting (33% vs 16%), pyrexia (29% vs 19%), fatigue (29% vs 26%), lymphopenia (24% vs 17%), anorexia (23% vs 10%), asthenia (21% vs 18%), cough (21% vs 13%), insomnia (20% vs 13%), edema peripheral (20% vs 10%), rash (19% vs 7%), back pain (17% vs 18%), pneumonia (16% vs 11%), dizziness (16% vs 11%), dyspnea (15% vs 13%), headache (14% vs 10%), pain in extremity (14% vs 9%), abdominal pain (14% vs 7%), paresthesia (13% vs 4%), herpes zoster (13% vs 4%), bronchitis (13% vs 8%), hypokalemia (13% vs 7%), hypertension (13% vs 7%), abdominal pain upper (12% vs 9%), hypotension (12% vs 3%), dyspepsia (11% vs 7%), nasopharyngitis (11% vs 8%), bone pain (11% vs 10%), arthralgia (11% vs 15%) and pruritus (10% vs 5%).

About Millennium

Millennium: The Takeda Oncology Company, a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE, a first-in-class proteasome inhibitor, and has a robust clinical development pipeline of product candidates. Millennium Pharmaceuticals, Inc. was acquired by Takeda Pharmaceutical Company Ltd. in May, 2008. The Company’s research, development and commercialization activities are focused in oncology. Additional information about Millennium is available through its website,

Source: Millennium: The Takeda Oncology Company

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