Celgene Corporation Release: REVLIMID(R) (Lenalidomide) Evaluated As Combination Oral Treatment Regimen In Elderly Newly Diagnosed Multiple Myeloma
ATLANTA, June 5 /PRNewswire-FirstCall/ -- Celgene Corporation announced that clinical data from a study with combination therapy lenalidomide, melphalan and prednisone (R-MP) in elderly newly diagnosed multiple myeloma patients were reported at an oral presentation during the 42nd American Society of Clinical Oncology (ASCO) Meeting in Atlanta, Georgia, on Monday June 5, 2006. The updated study data reported that after seven treatment cycles with R-MP all patients showed a response with no further disease progressions observed, and event-free survival (EFS) (p<0.001) after 9.6 month of follow-up.
REVLIMID is now approved by the FDA for treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities.
"The results from this study are the basis for a pivotal program to be initiated using R-MP in newly diagnosed multiple myeloma later this year," said Jerome B. Zeldis, M.D., Ph.D., Chief Medical Officer of Celgene Corporation.
About the Trial
The trial was designed to evaluate the potential additive and synergistic effects of the combination of R-MP, to define the toxicity profile of R-MP and to analyze the efficacy of this combination in patients with newly diagnosed symptomatic multiple myeloma aged 65 and older. Patients were treated with nine courses of lenalidomide (5-10 mg/day for 21 days every 4-6 weeks) plus MP (melphalan 0.18-0.25 mg/kg and prednisone 2 mg/kg for 4 days every 4-6 weeks). Four different dose levels were tested: 1) Melphalan 0.18 mg/kg + lenalidomide 5 mg/day; 2) Melphalan 0.25 mg/kg + lenalidomide 5 mg/day; 3) Melphalan 0.18 mg/kg + lenalidomide 10 mg/day; 4) Melphalan 0.25 mg/kg + lenalidomide 10 mg/day. Each cohort included 6 patients. Dose limiting toxicity (DLT) was defined as any non-hematologic toxicity equal to or greater than grade 3 according to NCI toxicity rating scale; grade 4 neutropenia lasting more than seven days; any other grade 4 hematologic toxicity and any treatment delay due to toxicity that occurred during the first cycle. All patients received ciprofloxacin and aspirin as prophylaxis.
Fifty three patients (median age 71, range 57-77) received at least one R-MP course. No DLTs were observed in the first 2 dose levels. In level 3 one patient experienced DLT (grade 4 neutropenia lasting> 7 days). In level 4 three patients showed DLTs (1 pt experienced neutropenic fever and grade 3 cutaneous toxicity, 1 pt had a pulmonary embolism and delayed cycle 2 due to neutropenia, 1 pt delayed cycle 2 due to hematological toxicity). After one cycle of R-MP, no one was in complete remission (CR) (according to the EBMT/IBMTR criteria), near complete response (nCR) in myeloma protein reduction of 75-99% was reported in 2.5% of patients, partial response (PR) in myeloma protein reduction of 50-74% was reported in 62.5% of patients and near partial response of less than 50% in myeloma protein reduction was reported in 27.5% of patients; After seven cycles of R-MP, CR was observed in 17.1% of patients, nCR was observed in 24.4% of patients, PR was observed in 43.9% of patients and nPR was observed in 14.6% of patients; no disease progressions were observed
Grade 3/4 hematological toxicities included neutropenia (66%), thrombocytopenia (34%) and anemia (17%). Grade 3/4 non-hematological toxicities included cutaneous eruption (10%), infections (5%), and febrile neutropenia (8%).
SAFETY NOTICE: WARNINGS: 1. POTENTIAL FOR HUMAN BIRTH DEFECTS.
LENALIDOMIDE IS AN ANALOGUE OF THALIDOMIDE. THALIDOMIDE IS A KNOWN HUMAN TERATOGEN THAT CAUSES SEVERE LIFE-THREATENING HUMAN BIRTH DEFECTS. IF LENALIDOMIDE IS TAKEN DURING PREGNANCY, IT MAY CAUSE BIRTH DEFECTS OR DEATH TO AN UNBORN BABY. FEMALES SHOULD BE ADVISED TO AVOID PREGNANCY WHILE TAKING REVLIMID(R) (lenalidomide).
Special Prescribing Requirements
BECAUSE OF THIS POTENTIAL TOXICITY AND TO AVOID FETAL EXPOSURE TO REVLIMID(R) (lenalidomide), REVLIMID(R) (lenalidomide) IS ONLY AVAILABLE UNDER A SPECIAL RESTRICTED DISTRIBUTION PROGRAM. THIS PROGRAM IS CALLED "RevAssist(SM)". UNDER THIS PROGRAM, ONLY PRESCRIBERS AND PHARMACISTS REGISTERED WITH THE PROGRAM ARE ABLE TO PRESCRIBE AND DISPENSE THE PRODUCT. IN ADDITION, REVLIMID(R) (lenalidomide) MUST ONLY BE DISPENSED TO PATIENTS WHO ARE REGISTERED AND MEET ALL THE CONDITIONS OF THE RevAssist(SM) PROGRAM.
2. HEMATOLOGIC TOXICITY (NEUTROPENIA AND THROMBOCYTOPENIA).
THIS DRUG IS ASSOCIATED WITH SIGNIFICANT NEUTROPENIA AND THROMBOCYTOPENIA IN PATIENTS WITH DEL 5q MDS. EIGHTY PERCENT OF PATIENTS HAD TO HAVE A DOSE DELAY/REDUCTION DURING THE MAJOR STUDY FOR THE DEL 5q MDS INDICATION. THIRTY- FOUR PERCENT OF PATIENTS HAD TO HAVE A SECOND DOSE DELAY/REDUCTION. GRADE 3 OR 4 HEMATOLOGIC TOXICITY WAS SEEN IN 80% OF PATIENTS ENROLLED IN THE STUDY. PATIENTS ON THERAPY SHOULD HAVE THEIR COMPLETE BLOOD COUNTS MONITORED WEEKLY FOR THE FIRST 8 WEEKS OF THERAPY AND AT LEAST MONTHLY THEREAFTER. PATIENTS MAY REQUIRE DOSE INTERRUPTION AND/OR REDUCTION. PATIENTS MAY REQUIRE USE OF BLOOD PRODUCT SUPPORT AND/OR GROWTH FACTORS. (SEE DOSAGE AND ADMINISTRATION)
3. DEEP VENOUS THROMBOSIS AND PULMONARY EMBOLISM.
THIS DRUG HAS DEMONSTRATED A SIGNIFICANTLY INCREASED RISK OF DEEP VENOUS THROMBOSIS (DVT) AND PULMONARY EMBOLISM (PE) IN PATIENTS WITH MULTIPLE MYELOMA WHO WERE TREATED WITH REVLIMID(R) (lenalidomide) COMBINATION THERAPY. PATIENTS AND PHYSICIANS ARE ADVISED TO BE OBSERVANT FOR THE SIGNS AND SYMPTOMS OF THROMBOEMBOLISM. PATIENTS SHOULD BE INSTRUCTED TO SEEK MEDICAL CARE IF THEY DEVELOP SYMPTOMS SUCH AS SHORTNESS OF BREATH, CHEST PAIN, OR ARM OR LEG SWELLING. IT IS NOT KNOWN WHETHER PROPHYLACTIC ANTICOAGULATION OR ANTIPLATELET THERAPY PRESCRIBED IN CONJUNCTION WITH REVLIMID(R) (lenalidomide) MAY LESSEN THE POTENTIAL FOR VENOUS THROMBOEMBOLIC EVENTS. THE DECISION TO TAKE PROPHYLACTIC MEASURES SHOULD BE DONE CAREFULLY AFTER AN ASSESSMENT OF AN INDIVIDUAL PATIENT'S UNDERLYING RISK FACTORS.
You can get information about REVLIMID(R) (lenalidomide) and the RevAssist(SM) program on the Internet at http://www.REVLIMID.com or by calling the manufacturer's toll-free number at 1-888-423-5436.
IMPORTANT SAFETY INFORMATION
Hypersensitivity: REVLIMID(R) (lenalidomide) is contraindicated in any patients who have demonstrated hypersensitivity to the drug or its components.
Renal impairment: REVLIMID(R) (lenalidomide) is substantially excreted by the kidney, so the risk of toxic reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it would be prudent to monitor renal function.
Nursing mothers: It is not known whether REVLIMID(R) (lenalidomide) is excreted in human milk. Because of the potential for adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.
Other adverse events reported in greater than or equal to 15% of del 5q MDS patients: diarrhea (49%), pruritus (42%), rash (36%), fatigue (31%), constipation (24%), nausea (24%), nasopharyngitis (23%), arthralgia (22%), pyrexia (21%), back pain (21%), peripheral edema (20%), cough (20%), dizziness (20%), headache (20%), muscle cramp (18%), dyspnea (17%), and pharyngitis (16%).
About REVLIMID(R)
REVLIMID is a member of a proprietary group of novel immunomodulatory compounds, IMiDs(R). Celgene continues to evaluate REVLIMID in a broad range of hematology and oncology conditions. The IMiD pipeline, including REVLIMID, is covered by a comprehensive intellectual property estate of U.S. and foreign issued and pending patent applications including composition-of-matter and use patents.
REVLIMID is approved by the FDA for treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. REVLIMID is not approved by the FDA or any other regulatory agencies as a treatment for any other indication and is currently being evaluated in clinical trials for efficacy and safety for future regulatory applications.
About RevAssist(SM)
FOR FURTHER INFORMATION ABOUT REVLIMID(R) AND THE RevAssist(SM) PROGRAM, YOU MAY GO TO THE INTERNET AT www.REVLIMID.com OR BY CALLING THE MANUFACTURER'S TOLL FREE NUMBER 1-888-4CELGENE. RevAssist(SM) is a proprietary risk-management restrictive distribution program, tailored specifically for REVLIMID patients, to prevent the potential for human birth defects and ensure prompt and convenient access to REVLIMID.
About Multiple Myeloma
Multiple myeloma (also known as myeloma or plasma cell myeloma) is a cancer of the blood in which malignant plasma cells are overproduced in the bone marrow. Plasma cells are white blood cells that help produce antibodies called immunoglobulins that fight infection and disease. However, most patients with multiple myeloma have cells that produce a form of immuno- globulin called paraprotein (or M protein) that does not benefit the body. In addition, the malignant plasma cells replace normal plasma cells and other white blood cells important to the immune system. Multiple myeloma cells can also attach to other tissues of the body, such as bone, and produce tumors. The cause of the disease remains unknown.
As the second most common blood cancer, multiple myeloma accounts for a reported worldwide prevalence of approximately 200,000 cases. In 2005, there were an estimated 74,000 new cases of multiple myeloma worldwide, and it is estimated that 60,000 people will die from multiple myeloma in 2006.
About Celgene
Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit the Company's website at http://www.celgene.com.
REVLIMID(R) is a registered trademark of Celgene Corporation.
RevAssist(SM) is a service mark of Celgene Corporation.
This release contains forward-looking statements which are subject to known and unknown risks, delays, uncertainties and other factors not under the Company's control, which may cause actual results, performance or achievements of the Company to be materially different from the results, performance or other expectations expressed or implied by these forward-looking statements. These factors include results of current or pending research and development activities, actions by the FDA and other regulatory authorities, and other factors described in the Company's filings with the Securities and Exchange Commission such as our 10K, 10Q and 8K reports.
Celgene CorporationCONTACT: Robert J. Hugin, President and COO, +1-908-673-9102, or Brian P.Gill, Senior Director PR-IR, +1-908-673-9530, both of Celgene Corporation