Summit, NJ (Press Release) – Celgene Corpo­ra­tion (NASDAQ: CELG) today announced results from an open-label phase II/III National Clinical Trials Network (NCTN) study led by the ECOG-ACRIN Cancer Research Group and sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health. REVLIMID® (lena­lido­mide) was provided by Celgene under a clin­i­cal trials agree­ment with the NCI’s Division of Cancer Treatment and Diagnosis.

ECOG E3A06 is a ran­dom­ized study eval­u­ating the safety and efficacy of the inves­ti­ga­tional use of REVLIMID mono­therapy versus observation in patients with asymptomatic smol­der­ing multiple myeloma. In the study, single-agent REVLIMID achieved a statistically sig­nif­i­cant im­prove­ment in the pri­mary end­point of pro­gres­sion-free survival compared to observation.

Based on the pre­lim­i­nary results of the study, safety was con­sis­tent with the known safety profile of REVLIMID®.

“In multiple myeloma, there has been an im­por­tant question re­gard­ing the risks and benefits of treating patients with smol­der­ing myeloma. We believe that the properties of REVLIMID could play an im­por­tant role in delaying the pro­gres­sion of smol­der­ing myeloma into active myeloma,” said Jay Backstrom, Chief Medical Officer for Celgene.

Data from ECOG E3A06 will be presented at a future medical meeting.

REVLIMID is not approved for use in asymptomatic smol­der­ing multiple myeloma in any geography.

About REVLIMID®

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

REVLIMID is indicated as main­te­nance ther­apy in patients with MM fol­low­ing au­tol­o­gous hema­to­poietic stem cell trans­plan­ta­tion (auto-HSCT)

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 is 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.

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 risk to the fetus

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

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity: See Boxed WARNINGS

• Females of Reproductive Potential: See Boxed WARNINGS
• 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 4 weeks 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 4 weeks 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: See Boxed WARNINGS: Prescribers and pharmacies must be certified with the REVLIMID REMS pro­gram by enrolling and complying with the REMS require­ments; pharmacies must only dispense to patients who are authorized to receive REVLIMID. Patients must sign a Patient-Physician Agreement Form and comply with REMS require­ments; female patients of reproductive poten­tial who are not pregnant must comply with the pregnancy testing and con­tra­cep­tion require­ments and males must comply with con­tra­cep­tion require­ments

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 or REVLIMID as main­te­nance ther­apy 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. MDS: 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 dose reduction. Please see the Black Box WARNINGS for further in­­for­ma­tion. 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

Venous and Arterial Thromboembolism: See Boxed WARNINGS: Venous thrombo­embolic events (DVT and PE) and arterial thromboses (MI and CVA) are in­­creased in patients treated with REVLIMID. 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). Thrombo­pro­phy­laxis is recommended and the regi­men should be based on patient’s under­lying risks. ESAs and estrogens may further in­­crease the risk of thrombosis and their use should be based on a benefit-risk de­ci­sion

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. Serious adverse cardiovascular reac­tions, in­­clud­ing atrial fibrillation, myo­cardial infarction, and cardiac failure, occurred more frequently in the REVLIMID arm. REVLIMID is not indicated and not recommended for use in CLL outside of controlled clin­i­cal trials

Second Primary Malignancies (SPM): In clin­i­cal trials in patients with MM receiving REVLIMID, an in­­crease of hema­to­logic plus solid tumor SPM, notably AML and MDS, have been observed. Monitor patients for the devel­op­ment of SPM. Take into account both the poten­tial benefit of REVLIMID and risk of SPM when con­sidering treat­ment

Increased Mortality with Pembrolizumab: In clin­i­cal trials in patients with multiple myeloma, the addi­tion of pem­bro­lizu­mab to a thalido­mide analogue plus dexa­meth­a­sone resulted in in­­creased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking anti­body in com­bi­na­tion with a thalido­mide analogue plus dexa­meth­a­sone is not recommended outside of controlled clin­i­cal trials

Hepatotoxicity: Hepatic failure, in­­clud­ing fatal cases, has occurred in patients treated with REVLIMID/dex. 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

Severe Cutaneous Reactions Including Hypersensitivity Reactions: Angioedema and severe cutaneous reac­tions in­­clud­ing Stevens-Johnson syn­drome (SJS), toxic epider­mal necrolysis (TEN), and drug reac­tion with eosinophilia and systemic symp­toms (DRESS) have been reported. DRESS may present with a cutaneous reac­tion (such as rash, or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic com­pli­ca­tions such as hepatitis, nephritis, pneu­mo­nitis, myocarditis, and/or pericarditis. 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, TEN, or DRESS is sus­pected and should not be resumed fol­low­ing dis­con­tinu­a­tion for these reac­tions

Tumor Lysis Syndrome (TLS): Fatal instances of 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 (TFR): TFR has occurred during inves­ti­ga­tional use of lena­lido­mide for CLL and lym­phoma. 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 REVLIMID until TFR resolves to ≤Grade 1. REVLIMID may be con­tinued in patients with Grade 1 and 2 TFR without inter­rup­tion or modification, at the physician’s discretion

Impaired Stem Cell Mobilization: A de­crease in the number of CD34+ cells collected after treat­ment (>4 cycles) with REVLIMID has been reported. Consider early referral to trans­plant center to optimize timing of the stem cell collection

Thyroid Disorders: Both hypo­thy­roid­ism and hyperthyroidism have been reported. Measure thyroid function before start of REVLIMID treat­ment and during ther­apy

Early Mortality in Patients with MCL: In another MCL study, there was an in­­crease in early deaths (within 20 weeks), 12.9% in the REVLIMID arm versus 7.1% in the control arm. Risk factors for early deaths in­clude high tumor burden, MIPI score at diag­nosis, and high WBC at base­line (≥10 x 109/L)

ADVERSE REACTIONS

Multiple Myeloma

• In newly diagnosed: The most frequently reported Grade 3 or 4 reactions included neutropenia, anemia, thrombocytopenia, pneumonia, asthenia, fatigue, back pain, hypokalemia, rash, cataract, lymphopenia, dyspnea, DVT, hyperglycemia, and leukopenia. The highest frequency of infections occurred in Arm Rd Continuous (75%) compared to Arm MPT (56%). There were more Grade 3 and 4 and serious adverse reactions of infection in Arm Rd Continuous than either Arm MPT or Rd18
• The most common adverse reactions reported in ≥20% (Arm Rd Continuous): diarrhea (46%), anemia (44%), neutropenia (35%), fatigue (33%), back pain (32%), asthenia (28%), insomnia (28%), rash (26%), decreased appetite (23%), cough (23%), dyspnea (22%), pyrexia (21%), abdominal pain (21%), muscle spasms (20%), and thrombocytopenia (20%)
• Maintenance Therapy Post Auto-HSCT: The most frequently reported Grade 3 or 4 reactions in ≥20% (REVLIMID arm) included neutropenia, thrombocytopenia, and leukopenia. The serious adverse reactions of lung infection and neutropenia (more than 4.5%) occurred in the REVLIMID arm
• The most frequently reported adverse reactions in ≥20% (REVLIMID arm) across both maintenance studies (Study 1, Study 2) were neutropenia (79%, 61%), thrombocytopenia (72%, 24%), leukopenia (23%, 32%), anemia (21%, 9%), upper respiratory tract infection (27%, 11%), bronchitis (5%, 47%), nasopharyngitis (2%, 35%), cough (10%, 27%), gastroenteritis (0%, 23%), diarrhea (55%, 39%), rash (32%, 8%), fatigue (23%, 11%), asthenia (0%, 30%), muscle spasm (0%, 33%), and pyrexia (8%, 21%)
• After at least one prior therapy: The most common adverse reactions reported in ≥20% (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%), and weight decreased (20% vs 15%)

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%)
• 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 is recommended due to in­­creased Cmax and AUC with concomitant REVLIMID ther­apy. Patients taking concomitant ther­a­pies such as erythropoietin stimulating agents or estrogen con­taining ther­a­pies may have an in­­creased risk of thrombosis. It is not known whether there is an inter­action be­tween dex and warfarin. Close monitoring of PT and INR is recommended in patients with MM taking concomitant warfarin

USE IN SPECIFIC POPULATIONS

• PREGNANCY: See Boxed WARNINGS: If pregnancy does occur during treatment, immediately discontinue the drug and refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. There is a REVLIMID pregnancy exposure registry that monitors pregnancy outcomes in females exposed to REVLIMID during pregnancy as well as female partners of male patients who are exposed to REVLIMID. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to REVLIMID to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation at 1-888-423-5436
• LACTATION: There is no information regarding the presence of lenalidomide in human milk, the effects of REVLIMID on the breastfed infant, or the effects of REVLIMID on milk production. Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants from REVLIMID, advise female patients not to breastfeed during treatment with REVLIMID
• PEDIATRIC USE: Safety and effectiveness have not been established in pediatric patients
• RENAL IMPAIRMENT: Adjust the starting dose of REVLIMID based on the creatinine clearance value and in patients on dialysis

Please see full Prescribing Information, in­­clud­ing Boxed WARNINGS.

About the ECOG-ACRIN Cancer Research Group

The ECOG-ACRIN Cancer Research Group is a membership-based scientific organization that designs and conducts cancer research involving adults who have or are at risk of devel­op­ing cancer. ECOG-ACRIN com­prises nearly 1,100 member institutions in the United States and around the world. Approximately 12,000 physicians, translational scientists, and asso­ci­ated research professionals from the member institutions are involved in Group research, which is organized into three scientific pro­grams: Cancer Control and Outcomes, Therapeutic Studies, and Biomarker Sciences. ECOG-ACRIN is sup­ported primarily through National Cancer Institute research grant funding, but also receives funding from private sector organizations through philanthropy and col­lab­o­rations. It is headquartered in Philadelphia, Pa. For more in­­for­ma­tion, visit ecog-acrin.org or call 215.789.3631.

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 next-generation solu­tions in protein homeo­stasis, immuno-oncology, epigenetics, immunology and neuro-inflammation. For more in­­for­ma­tion, please visit www.celgene.com. Follow Celgene on Social Media: @Celgene, Pinterest, LinkedIn, Facebook and YouTube.

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 our Annual Report on Form 10-K and our other reports filed with the Securities and Exchange Com­mis­sion.

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Source: Celgene.