Celgene Corporation
Jun 16, 2011
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Phase I/II Data Evaluating Clinical Benefit of REVLIMID® in Combination with Standard R-CHOP Chemotherapy for Patients with Untreated Diffuse Large B-Cell Lymphoma

Phase I/II Study Reports 100% Overall Response Rate and 83% Complete Response Rate High Complete Remission Rates and Safety in Elderly Patients Supported by Second Phase I Study

BOUDRY, Switzerland, Jun 16, 2011 (BUSINESS WIRE) --

Celgene International Sàrl (NASDAQ: CELG) announced that clinical data from two studies evaluating the use of REVLIMID® (lenalidomide) with standard R-CHOP* chemotherapy (R2CHOP) in patients with untreated diffuse large B cell (DLBCL) or grade 3 follicular lymphoma were presented at the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland.

In a phase I/II study conducted by investigators at the Mayo Clinic, 12 patients received REVLIMID at doses of 15 mg, 20 mg or 25 mg on days 1-10 of each 21-day cycle with standard R-CHOP chemotherapy to determine the maximum tolerated dose (MTD) of REVLIMID. There were no dose-limiting toxicities observed.

In the phase II portion, 32 evaluable patients received 25 mg of REVLIMID on days 1-10 administered with standard R-CHOP chemotherapy (R2CHOP) for up to six cycles. Twenty-eight patients had DLBCL and four patients had grade 3 follicular lymphoma. The age range was 19 to 87 years.

Responses were evaluated using PET/CT. Out of 30 evaluable patients, the overall response rate was 100% and the complete response rate was 83%. Additionally, the 12-month event-free survival for patients in the study (N=32) was 75.1% (95% CI: 60.3-93.7%).

The most common hematological toxicities were grade 3/4 thrombocytopenia (16%/25%) and grade 3/4 neutropenia (13%/75%).

In a similarly designed phase I study conducted by the Fondazione Italiana Linfomi (FIL) in elderly patients with untreated DLBCL, REVLIMID was combined with R-CHOP* (LR-CHOP21). Twenty-one patients received REVLIMID at doses of 10 mg, 15 mg, or 20 mg on days 1-14 of each 21-day cycle with standard R-CHOP chemotherapy to determine the maximum tolerated dose (MTD) of REVLIMID®. With this particular schedule, REVLIMID at a dose of 15mg was determined to be the MTD. The age range was 61 to 77 years.

Response was evaluated using PET/CT, and of 21 evaluable patients, the overall response rate was 86% and the complete response rate was 76% after 6-cycles of LR-CHOP21.

The most common grade 3 or higher hematological toxicities were neutropenia (28%) and thrombocytopenia (10%), and the most common non-hematologic toxicities greater grade 3 or higher were neuropathy (14%) and infections (14%).

These data are from an investigational study. REVLIMID is not approved as a treatment for patients with DLBCL or follicular grade III lymphoma.

* cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab

About REVLIMID®

REVLIMID® is an IMiDs® compound. REVLIMID and other IMiDs continue to be evaluated in over 100 clinical trials. The IMiDs pipeline is covered by a comprehensive intellectual property estate of issued and pending patent applications in the US, EU and other regions, including composition-of-matter and use patents.

REVLIMID is approved in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy in nearly 70 countries, encompassing Europe, the Americas, the Middle-East and Asia, and in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy in Australia and New Zealand.

REVLIMID is also approved in the United States, Canada and several Latin American countries, as well as Malaysia and Israel, for transfusion-dependent anaemia due to low- or intermediate-1-risk MDS associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. Marketing Authorization Applications are currently being evaluated in a number of other countries.

Important Safety Information

REVLIMID® (lenalidomide) in combination with dexamethasone is indicated for the treatment of multiple myeloma (MM) patients who have received at least one prior therapy.

REVLIMID is indicated for patients with transfusion-dependent anaemia due to Low- or Intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities.

Important Safety Information

WARNING: FETAL RISK, HEMATOLOGIC TOXICITY, and DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM

Do not use REVLIMID during pregnancy. Lenalidomide, a thalidomide analogue, caused limb abnormalities in a developmental monkey study. Thalidomide is a known human teratogen that causes severe life-threatening human birth defects. If lenalidomide is used during pregnancy, it may cause birth defects or death to a developing baby. In women of childbearing potential, obtain 2 negative pregnancy tests before starting REVLIMID treatment. Women of childbearing potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after REVLIMID treatment. To avoid fetal exposure to lenalidomide, REVLIMID is only available under a restricted distribution program called "RevAssist®."

Information about the RevAssist program is available at www.REVLIMID.com or by calling the manufacturer's toll-free number 1-888-423-5436.

HEMATOLOGIC TOXICITY (NEUTROPENIA AND THROMBOCYTOPENIA)

REVLIMID can cause significant neutropenia and thrombocytopenia. Eighty percent of patients with del 5q MDS had to have a dose delay/reduction during the major study. 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 for del 5q MDS 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)

DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM

REVLIMID has demonstrated a significantly increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with MM who were treated with REVLIMID and dexamethasone 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 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.

CONTRAINDICATIONS:

Pregnancy Category X:

Allergic Reactions:

WARNINGS AND PRECAUTIONS:

Fetal Risk:

Reproductive Risk and Special Prescribing Requirements (RevAssist Program):

Haematologic Toxicity--Multiple Myeloma:

Deep Vein Thrombosis:

Allergic Reactions:

Tumour Lysis Syndrome:

Tumour Flare Reaction:

DRUG INTERACTIONS:

USE IN SPECIAL POPULATIONS:

Nursing Mothers:

Geriatric Use:

Renal Impairment:

ADVERSE REACTIONS:

Multiple Myeloma

Myelodysplastic Syndromes

DOSAGE AND ADMINISTRATION:

Please see full Prescribing Information, including Boxed WARNINGS, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS.

About Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) describes the appearance of the malignant B-cells in the lymphoma and it is the most frequently occurring lymphoma subtype in adults, constituting approximately 31% of all new diagnoses. The vast majority of relapses occur in the first 2 years after therapy. Life expectancy of untreated patients with DLBCL is very short, and while R-CHOP chemotherapy can result in complete remissions, approximately 40% of patients will ultimately relapse.

About ADCC (antibody-dependent cell-mediated cytotoxicity)

ADCC is an immune defense mechanism that directs natural killer cells, T cells, macrophages and other immune cells to cause cancer cell death. Antibodies such as rituximab target receptors on lymphoma cells to induce ADCC. In addition to being an immunomodulatory agent with direct and indirect cancer activity, REVLIMID® may also enhance the ADCC process against cancer cells.

About Celgene Risk-Management

Celgene continues to be a pioneer in creating environments in which patients who can benefit from our disease-altering therapies are able to do so, and do so safely. We are fully committed to drug lifecycle safety, from clinical development to post-marketing surveillance. As a result, patients worldwide continue to benefit from our risk-management programs such as, S.T.E.P.S.®, RevAssist®, RevMate® and PRMP, which form the global foundation of our commitment to patient safety.

About Celgene International Sàrl

Celgene International Sàrl, located in Boudry, in the Canton of Neuchâtel, Switzerland, is a wholly owned subsidiary and international headquarters of Celgene Corporation. 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 www.celgene.com.

This release contains certain forward-looking statements which involve known and unknown risks, delays, uncertainties and other factors not under the Company's control. The Company's actual results, performance, or achievements could be materially different from those projected by these forward-looking statements.The factors that could cause actual results, performance, or achievements to differ from the forward-looking statements are discussed in the Company's filings with the Securities and Exchange Commission, such as the Company's Form 10-K, 10-Q and 8-K reports.Given these risks and uncertainties, you are cautioned not to place undue reliance on the forward-looking statements.

SOURCE: Celgene International Sàrl

Celgene International Sàrl
Kevin Loth, +41 32 729 86 21
Director of External Relations