REVLIMID plus dexa­meth­a­sone is now approved as an option for use in all patients with multiple myeloma

Summit, NJ (Press Release) – Celgene Corpo­ra­tion (NASDAQ:CELG) today announced that the U.S. Food and Drug Admin­istra­tion (FDA) has expanded the existing indi­ca­tion for REVLIMID® (lena­lido­mide) in com­bi­na­tion with dexa­meth­a­sone to in­clude patients newly diag­nosed with multiple myeloma (NDMM). REVLIMID plus dexa­meth­a­sone was pre­vi­ously approved in June 2006 for use in multiple myeloma patients who have received at least one prior ther­apy.

"The approval of REVLIMID as an option for use in all patients with multiple myeloma rep­re­sents a new paradigm in the man­agement of this disease," said Kenneth Anderson, M.D., Director, Jerome Lipper Multiple Myeloma Center, Dana-Farber/Brigham and Women's Cancer Center. "We now have clin­i­cal evi­dence demonstrating that starting and keeping newly diag­nosed multiple myeloma patients on REVLIMID sig­nif­i­cantly im­proves pro­gres­sion-free survival."

The approval was based on safety and efficacy results from phase III studies, in­­clud­ing the FIRST trial (MM-020/IFM 07-01), which eval­u­ated continuous REVLIMID in com­bi­na­tion with dexa­meth­a­sone (Rd Continuous) until disease pro­gres­sion versus mel­phalan, pred­ni­sone and thalido­mide (MPT) for 18 months as the pri­mary analysis, and a fixed duration of 18 cycles of Rd (Rd18) as a sec­ond­ary analysis, in 1,623 newly diag­nosed patients who were not can­di­dates for stem cell trans­plant.

In this ran­dom­ized, open-label, three-arm trial, median pro­gres­sion-free survival (PFS), the length of time a patient lives from study ran­domization to disease pro­gres­sion or death was the pri­mary end­point of the study. PFS was sig­nif­i­cantly longer for patients receiving Rd Continuous (25.5 months) than for those treated with MPT (21.2 months; HR=0.72; p=0.0001). Median over­all survival (OS) in the two groups was 58.9 months and 48.5 months, re­spec­tive­ly (HR 0.75; 95% CI 0.62, 0.90) based on a March 3, 2014 interim OS analysis. Patients in the Rd Continuous arm had a 25% reduction in the risk of death compared to patients in the MPT arm.

Safety results showed that adverse reac­tions reported in ≥20% of NDMM patients in the Rd Continuous, Rd18 or MPT arms in­cluded diarrhea (45.5%, 38.5%, 16.5%), anemia (43.8%, 35.7%, 42.3%), neu­tro­penia (35.0%, 33.0%, 60.6%), fatigue (32.5%, 32.8%, 28.5%), back pain (32.0%, 26.9%, 21.4%), insomnia (27.6%, 23.5%, 9.8%), asthenia (28.2%, 22.8%, 22.9%), rash (26.1%, 28.0%, 19.4%), de­creased appetite (23.1%, 21.3%, 13.3%), cough (22.7%, 17.4%, 12.6%), pyrexia (21.4%, 18.9%, 14.0%), muscle spasms (20.5%, 18.9%, 11.3%) and abdominal pain (20.5%, 14.4%, 11.1%).

The most frequently reported Grade 3 or 4 events in the Rd Continuous arm (until disease pro­gres­sion) in­cluded neu­tro­penia (27.8%), anemia (18.2%), thrombo­cytopenia (8.3%), pneu­monia (11.3%), asthenia (7.7%), fatigue (7.3%), back pain (7%), hypokalemia (6.6%), rash (7.3%), cataract (5.8%), dyspnea (5.6%), DVT (5.6%) and hyperglycemia (5.3%).

"At Celgene, we are very happy with the FDA's de­ci­sion, which adds in­­for­ma­tion on the use of REVLIMID plus dexa­meth­a­sone as a first-line treat­ment for multiple myeloma to the pre­scrib­ing in­­for­ma­tion," said Jacqualyn A. Fouse, Ph.D., Pres­i­dent, Global Hematology and Oncology for Celgene. "Now, as part of our commitment to im­prov­ing the lives of patients living with this disease, our next step is to make the benefits of this treat­ment regi­men avail­able to those now eli­gible under the expanded indi­ca­tion."

Celgene cur­rently has an appli­ca­tion under review with the European Medicines Agency (EMA) for approval to use REVLIMID for the treat­ment of adult patients with pre­vi­ously untreated multiple myeloma who are not eli­gible for trans­plant. The EMA's Committee for Medicinal Products for Human Use (CHMP) published a positive opinion for this appli­ca­tion in December 2014.

About REVLIMID®

In the United States, REVLIMID is approved in com­bi­na­tion with dexa­meth­a­sone for the treat­ment of patients with multiple myeloma. REVLIMID is also 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, Switzerland, Australia, New Zealand and several Latin American countries, as well as Malaysia and Israel, for 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 and in Europe for the treat­ment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk MDS asso­ci­ated with an isolated deletion 5q cytogenetic ab­nor­mal­ity when other thera­peutic options are insufficient or inadequate.

In addi­tion, REVLIMID is approved in the United States for the treat­ment of patients with mantle cell lym­phoma (MCL) whose disease has re­lapsed or progressed after two prior ther­a­pies, one of which in­cluded bor­tez­o­mib.

U.S. Regulatory Information for REVLIMID®

REVLIMID® (lena­lido­mide) in com­bi­na­tion with dexa­meth­a­sone (dex) is indicated for the treat­ment of patients with multiple myeloma (MM)

REVLIMID® is indicated for the 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 indicated for the treat­ment of patients with mantle cell lym­phoma (MCL) whose disease has re­lapsed or progressed after two prior ther­a­pies, one of which in­cluded bor­tez­o­mib

REVLIMID is not indicated and not recommended for the treat­ment of patients with chronic lym­pho­cytic leukemia (CLL) outside of controlled clin­i­cal trials

Important Safety Information

WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and VENOUS and ARTERIAL THROMBOEMBOLISM

Embryo-Fetal Toxicity

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 embryo-fetal death. In females of reproductive poten­tial, obtain 2 negative pregnancy tests before starting REVLIMID treat­ment. Females of reproductive poten­tial must use 2 forms of con­tra­cep­tion or continuously abstain from heterosexual sex during and for 4 weeks after REVLIMID treat­ment. To avoid embryo-fetal exposure to lena­lido­mide, REVLIMID is only avail­able through a restricted distribution pro­gram, the REVLIMID REMS® pro­gram (formerly known as the "RevAssist®"program).

Information about the REVLIMID REMS® pro­gram is avail­able at www.celgeneriskmanagement.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.

Venous and Arterial Thromboembolism

REVLIMID has dem­onstrated a sig­nif­i­cantly in­­creased risk of deep vein thrombosis (DVT) and pul­mo­nary embolism (PE), as well as risk of myo­cardial infarction and stroke in patients with MM who were treated with REVLIMID and dexa­meth­a­sone ther­apy. Monitor for and advise patients about signs and symp­toms of thromboembolism. Advise patients to seek im­medi­ate medical care if they develop symp­toms such as shortness of breath, chest pain, or arm or leg swelling. Thrombo­pro­phy­laxis is recommended and the choice of regi­men should be based on an assess­ment of the patient's under­lying risks.

CONTRAINDICATIONS

Pregnancy: REVLIMID can cause fetal harm when admin­istered to a pregnant female and is con­tra­in­di­cated in females who are pregnant. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the poten­tial hazard to the fetus

Allergic Reactions: REVLIMID is con­tra­in­di­cated in patients who have dem­onstrated hypersensitivity (e.g., angioedema, Stevens-Johnson syn­drome, toxic epider­mal necrolysis) to lena­lido­mide

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity:

• REVLIMID is an analogue of thalidomide, a known human teratogen that causes life-threatening human birth defects or embryo-fetal death. An embryo-fetal development study in monkeys indicates that lenalidomide produced malformations in offspring of female monkeys who received drug during pregnancy, similar to birth defects observed in humans following exposure to thalidomide during pregnancy
• Females of Reproductive Potential: Must avoid pregnancy for at least 4 weeks before beginning REVLIMID therapy, during therapy, during dose interruptions and for at least 4 weeks after completing therapy. Must commit either to abstain continuously from heterosexual sexual intercourse or to use two methods of reliable birth control beginning 4 weeks prior to initiating treatment with REVLIMID, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of REVLIMID. Must obtain 2 negative pregnancy tests prior to initiating therapy
• Males: Lenalidomide is present in the semen of patients receiving the drug. Males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking REVLIMID and for up to 28 days after discontinuing REVLIMID, even if they have undergone a successful vasectomy. Male patients taking REVLIMID must not donate sperm
• Blood Donation: Patients must not donate blood during treatment with REVLIMID and for 1 month following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to REVLIMID

REVLIMID REMS® Program

Because of embryo-fetal risk, REVLIMID is avail­able only through a restricted pro­gram under a Risk Evaluation and Mitigation Strategy (REMS) the REVLIMID REMS® Program (formerly known as the "RevAssist®" Program). Prescribers and pharmacies must be certified with the pro­gram and patients must sign an agree­ment form and comply with the require­ments. Further in­­for­ma­tion about the REVLIMID REMS® pro­gram is avail­able at www.celgeneriskmanagement.com or by telephone at 1-888-423-5436

Hematologic Toxicity: REVLIMID can cause sig­nif­i­cant neu­tro­penia and thrombo­cytopenia. Monitor patients with neu­tro­penia for signs of in­fec­tion. Advise patients to observe for bleeding or bruising, especially with use of concomitant medications that may in­­crease risk of bleeding. MM: Patients taking REVLIMID/dex should have their com­plete blood counts (CBC) assessed every 7 days for the first 2 cycles, on days 1 and 15 of cycle 3, and every 28 days there­after. MCL: Patients taking REVLIMID for MCL should have their CBCs monitored weekly for the first cycle (28 days), every 2 weeks during cycles 2-4, and then monthly there­after. Patients may require dose inter­rup­tion and/or dose reduction. MDS: See Boxed WARNINGS

Venous and Arterial Thromboembolism: Venous thrombo­embolic events (DVT and PE) and arterial thromboses are in­­creased in patients treated with REVLIMID. A sig­nif­i­cantly in­­creased risk of DVT (7.4%) and PE (3.7%) occurred in patients with MM after at least one prior ther­apy, treated with REVLIMID/dex compared to placebo/dex (3.1% and 0.9%) in clin­i­cal trials with varying use of anticoagulant ther­a­pies. In NDMM study, in which nearly all patients received antithrombotic prophylaxis, DVT (3.6%) and PE (3.8%) were reported in the Rd continuous arm. Myocardial infarction (MI,1.7%) and stroke (CVA,2.3%) are in­­creased in patients with MM after at least 1 prior ther­apy who were treated with REVLIMID/dex ther­apy compared with placebo/dex (0.6%, and 0.9%) in clin­i­cal trials. In NDMM study, MI (including acute) was reported (2.3%) in the Rd Continuous arm. Frequency of serious adverse reac­tions of CVA was (0.8%) in the Rd Continuous arm. Patients with known risk factors, in­­clud­ing prior thrombosis, may be at greater risk and actions should be taken to try to minimize all modifiable factors (e.g. hyperlipidemia, hyper­tension, smoking). In controlled clin­i­cal trials that did not use concomitant thrombo­pro­phy­laxis, 21.5% over­all thrombotic events occurred in patients with refractory and re­lapsed MM who were treated with REVLIMID/dex compared to 8.3% thrombosis in the placebo/dex group. Median time to first thrombosis event was 2.8 months. In NDMM study, which nearly all patients received antithrombotic prophylaxis, over­all frequency of thrombotic events was 17.4% in com­bined Rd continuous and Rd18 arms. Median time to first thrombosis event as 4.37 months. Thrombo­pro­phy­laxis is recommended and regi­men is based on patients under­lying risks. ESAs and estrogens may further in­­crease the risk of thrombosis and their use should be based on a benefit-risk de­ci­sion. See Boxed WARNINGS

Increased Mortality in Patients With CLL: In a clin­i­cal trial in the first line treat­ment of patients with CLL, single agent REVLIMID ther­apy in­­creased the risk of death as compared to single agent chlorambucil. In an interim analysis, there were 34 deaths among 210 patients on the REVLIMID treat­ment arm compared to 18 deaths among 211 patients in the chlorambucil treat­ment arm, and hazard ratio for over­all survival was 1.92 [95% CI: 1.08-3.41] con­sis­tent with a 92% in­­crease in risk of death. Serious adverse cardiovascular reac­tions, in­­clud­ing atrial fibrillation, myo­cardial infarction, and cardiac failure occurred more frequently in the REVLIMID treat­ment arm. REVLIMID is not indicated and not recommended for use in CLL outside of controlled clin­i­cal trials

Second Primary Malignancies: In clin­i­cal trials in patients with MM receiving REVLIMID, an in­­crease of in­­vasive second pri­mary malig­nan­cies notably AML and MDS have been observed. The in­­crease of AML and MDS occurred predominantly in NDMM patients receiving REVLIMID in com­bi­na­tion with oral mel­phalan (5.3%) or im­medi­ately fol­low­ing high dose in­tra­venous mel­phalan and ASCT (up to 5.2%). The frequency of AML and MDS cases in the Revlimid/dex arms was observed to be 0.4%. Cases of B-cell malig­nan­cies (including Hodgkin's Lymphomas) were observed in clin­i­cal trials where patients received lena­lido­mide in the post-ASCT setting. Patients who received REVLIMID-containing ther­apy until disease pro­gres­sion did not show a higher incidence of in­­vasive SPM than patients treated in the fixed duration REVLIMID-containing arms. Monitor patients for the devel­op­ment of second pri­mary malig­nan­cies. Take into account both the poten­tial benefit and risk of second pri­mary malig­nan­cies when con­sidering treat­ment with REVLIMID

Hepatotoxicity: Hepatic failure, in­­clud­ing fatal cases, has occurred in patients treated with lena­lido­mide in com­bi­na­tion with dex. The mech­a­nism of drug-induced hepato­tox­ic­ity is unknown. Pre-existing viral liver disease, elevated base­line liver enzymes, and concomitant medications may be risk factors. Monitor liver enzymes periodically. Stop REVLIMID upon elevation of liver enzymes. After return to base­line values, treat­ment at a lower dose may be con­sidered

Allergic Reactions: Angioedema and serious dermatologic reac­tions in­­clud­ing Stevens-Johnson syn­drome (SJS) and toxic epider­mal necrolysis (TEN) have been reported. These events can be fatal. Patients with a prior history of Grade 4 rash asso­ci­ated with thalido­mide treat­ment should not receive REVLIMID. REVLIMID inter­rup­tion or dis­con­tinu­a­tion should be con­sidered for Grade 2-3 skin rash. REVLIMID must be dis­con­tinued for angioedema, Grade 4 rash, exfoliative or bullous rash, or if SJS or TEN is sus­pected and should not be resumed fol­low­ing dis­con­tinu­a­tion for these reac­tions. REVLIMID capsules con­tain lactose. Risk-benefit of REVLIMID treat­ment should be eval­u­ated in patients with lactose intolerance

Tumor Lysis Syndrome: Fatal instances of tumor lysis syn­drome (TLS) have been reported during treat­ment with lena­lido­mide. The patients at risk of TLS are those with high tumor burden prior to treat­ment. These patients should be monitored closely and appro­pri­ate precautions taken

Tumor Flare Reaction: Tumor flare reac­tion (TFR) has occurred during inves­ti­ga­tional use of lena­lido­mide for CLL and lym­phoma, and is char­ac­ter­ized by tender lymph node swelling, low grade fever, pain and rash.

Monitoring and evaluation for TFR is recommended in patients with MCL. Tumor flare may mimic the pro­gres­sion of disease (PD). In patients with Grade 3 or 4 TFR, it is recommended to withhold treat­ment with lena­lido­mide until TFR resolves to ≤ Grade 1. In the MCL trial, approx­i­mately 10% of subjects ex­peri­enced TFR; all reports were Grade 1 or 2 in severity. All of the events occurred in cycle 1 and one patient developed TFR again in cycle 11. Lena­lido­mide may be con­tinued in patients with Grade 1 and 2 TFR without inter­rup­tion or modification, at the physician's discretion. Patients with Grade 1 or 2 TFR may also be treated with corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and/or narcotic analgesics for man­agement of TFR symp­toms. Patients with Grade 3 or 4 TFR may be treated for man­agement of symp­toms per the guidance for treat­ment of Grade 1 and 2 TFR

Impaired Stem Cell Mobilization: A de­crease in the number of CD34+ cells collected after treat­ment ( > 4 cycles) with REVLIMID has been reported. In patients who are au­tol­o­gous stem cell trans­plant (ASCT) can­di­dates, referral to a trans­plant center should occur early in treat­ment to optimize timing of the stem cell collection.

ADVERSE REACTIONS

Multiple Myeloma

• In newly diagnosed patients the most frequently reported Grade 3 or 4 adverse reactions in Arm Rd Continuous included neutropenia (27.8%), anemia (18.2%), thrombocytopenia (8.3%), pneumonia (11.1%), asthenia (7.7.%), fatigue (7.3%), back pain (7%), hypokalemia (6.6%), rash (7.3%), cataract (5.8%), dyspnea (5.6%), DVT (5.5%), hyperglycemia (5.3%), lymphopenia and leukopenia. The frequency of infections in Arm Rd Continuous was 75%

Adverse reac­tions reported in ≥20% of NDMM patients in Arm Rd Continuous: diarrhea (45.5%), anemia (43.8%), neu­tro­penia (35%), fatigue (32.5%), back pain (32%), insomnia (27.6%), asthenia (28.2%), rash (26.1%), de­creased appetite (23.1%), cough (22.7%), dyspnea (22.0%), pyrexia (21.4%), muscle spasms (20.5%), and abdominal pain (20.5%). The frequency of onset of cataracts in­­creased over time with 0.7% during the first 6 months and up to 9.6% by the second year of treat­ment with Arm Rd Continuous

• After at least one prior therapy most adverse reactions and Grade 3/4 adverse reactions were more frequent in MM patients who received the combination of REVLIMID/dex compared to placebo/dex. Grade 3 or 4 adverse reactions included neutropenia 33.4% vs 3.4%, febrile neutropenia 2.3% vs 0%, DVT 8.2% vs 3.4% and PE 4% vs 0.9% respectively

Adverse reac­tions reported in ≥15% of MM patients (REVLIMID/dex vs dex/placebo): fatigue (44% vs 42%), neu­tro­penia (42% vs 6%), con­sti­pa­tion (41% vs 21%), diarrhea (39% vs 27%), muscle cramp (33% vs 21%), anemia (31% vs 24%), pyrexia (28% vs 23%), periph­eral edema (26% vs 21%), nausea (26% vs 21%), back pain (26% vs 19%), upper res­pira­tory tract in­fec­tion (25% vs 16%), dyspnea (24% vs 17%), dizzi­ness (23% vs 17%), thrombo­cytopenia (22% vs 11%), rash (21% vs 9%), tremor (21% vs 7%), weight de­creased (20% vs 15%), nasopharyngitis (18% vs 9%), blurred vision (17% vs 11%), anorexia (16% vs 10%), and dysgeusia (15% vs 10%)

Myelodysplastic Syndromes

• Grade 3 and 4 adverse events reported in ≥ 5% of patients with del 5q MDS were neutropenia (53%), thrombocytopenia (50%), pneumonia (7%), rash (7%), anemia (6%), leukopenia (5%), fatigue (5%), dyspnea (5%), and back pain (5%)
• Adverse events reported in ≥15% of del 5q MDS patients (REVLIMID): thrombocytopenia (61.5%), neutropenia (58.8%), 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%), pharyngitis (16%), epistaxis (15%), asthenia (15%), upper respiratory tract infection (15%)

Mantle Cell Lymphoma

• Grade 3 and 4 adverse events reported in ≥5% of patients treated with REVLIMID in the MCL trial (N=134) included neutropenia (43%), thrombocytopenia (28%), anemia (11%), pneumonia (9%), leukopenia (7%), fatigue (7%), diarrhea (6%), dyspnea (6%), and febrile neutropenia (6%)
• Serious adverse events reported in ≥2 patients treated with REVLIMID monotherapy for MCL included chronic obstructive pulmonary disease, clostridium difficile colitis, sepsis, basal cell carcinoma, and supraventricular tachycardia
• Adverse events reported in ≥15% of patients treated with REVLIMID in the MCL trial included neutropenia (49%), thrombocytopenia (36%), fatigue (34%), anemia (31%), diarrhea (31%), nausea (30%), cough (28%), pyrexia (23%), rash (22%), dyspnea (18%), pruritus (17%), peripheral edema (16%), constipation (16%), and leukopenia (15%)

DRUG INTERACTIONS

Periodic monitoring of digoxin plasma levels, in accordance with clin­i­cal judgment and based on standard clin­i­cal practice in patients receiving this medication, is recommended during admin­istra­tion of REVLIMID. It is not known whether there is an inter­action be­tween dex and warfarin. Close monitoring of PT and INR is recommended in MM patients taking concomitant warfarin. Erythropoietic agents, or other agents, that may in­­crease the risk of thrombosis, such as estrogen con­taining ther­a­pies, should be used with caution after making a benefit-risk assess­ment in patients receiving REVLIMID

USE IN SPECIFIC POPULATIONS

Pregnancy: If pregnancy does occur during treat­ment, im­medi­ately dis­con­tinue the drug. Under these con­di­tions, refer patient to an obstetrician/gynecologist ex­peri­enced in reproductive toxicity for further evaluation and counseling. Any sus­pected fetal exposure to REVLIMID must be reported to the FDA via the MedWatch pro­gram at 1-800-332-1088 and also to Celgene Corpo­ra­tion at 1-888-423-5436

Nursing Mothers: It is not known whether REVLIMID is excreted in human milk. Because many drugs are excreted in human milk and 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

Pediatric Use: Safety and effectiveness in patients below the age of 18 have not been estab­lish­ed

Renal Impairment: Since REVLIMID is primarily excreted unchanged by the kidney, ad­just­ments to the starting dose of REVLIMID are recommended to provide appro­pri­ate drug exposure in patients with mod­er­ate (CLcr 30-60 mL/min) or severe renal im­pair­ment (CLcr < 30 mL/min) and in patients on dialysis

Please see accompanying full Prescribing Information, in­­clud­ing Boxed WARNINGS.

About Celgene

Celgene Corpo­ra­tion, headquartered in Summit, New Jersey, is an integrated global bio­pharma­ceu­tical 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 www.celgene.com. Follow us on Twitter @Celgene, and on Pinterest and LinkedIn.

Forward-Looking Statements

This press release con­tains forward-looking state­ments, which are generally state­ments that are not historical facts. Forward-looking state­ments can be identified by the words "expects," "antic­i­pates," "believes," "intends," "estimates," "plans," "will," "outlook" and similar ex­pres­sions. Forward-looking state­ments are based on man­agement's current plans, esti­mates, assump­tions and projections, and speak only as of the date they are made. We under­take no obli­ga­tion to update any forward-looking state­ment in light of new in­­for­ma­tion or future events, except as other­wise required by law. Forward-looking state­ments involve in­her­ent risks and un­cer­tain­ties, most of which are dif­fi­cult to predict and are generally beyond our control. Actual results or out­comes may differ ma­teri­ally from those implied by the forward-looking state­ments as a result of the impact of a number of factors, many of which are discussed in more detail in Celgene Corpo­ra­tion's Annual Report on Form 10-K and other reports filed with the Securities and Exchange Com­mis­sion.

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Source: Celgene Corpo­ra­tion.