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Celgene to Present New Clinical Data in Blood Cancer and Solid Tumor Therapies at Upcoming American Society of Clinical Oncology (ASCO) Scientific Sessions

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Presentations highlight the value of innovative research in key
disease areas including multiple myeloma, lymphoma, acute myeloid
leukemia and squamous non-small cell lung cancer, as well as novel CAR T
technology

Celgene Corporation (NASDAQ:CELG) today announced that data from more
than 60 company-sponsored, cooperative group and investigator-initiated
clinical studies evaluating Celgene agents will be presented at the
American Society of Clinical Oncology Annual Meeting between June 1-5 in
Chicago, Ill.

"Cancer research is at a critical point where advances in cellular
immunotherapy may be able to drive previously unattainable
advancements," said Nadim Ahmed, President, Hematology and Oncology for
Celgene. "The studies being shared at ASCO this year reinforce our
position of being at the forefront of discoveries that can accelerate
our understanding of disease mechanisms with the opportunity to harness
a patient's own immune system to maximize the potential of new
therapeutic options for patients."

In blood cancers, abstracts continue to support the role of Celgene's
IMiD® therapies as a foundation of multiple myeloma research. Multiple
studies highlighting key Celgene research collaborations of
investigational compounds will also be presented, including updated data
from the first clinical study of anti-BCMA CAR T therapy bb2121 in
multiple myeloma. In addition, results of the study evaluating the
investigational R2 regimen (REVLIMID® (lenalidomide) and rituximab
combination) as first-line therapy in previously-untreated follicular
lymphoma patients will also be presented. Experts will also share
results from a study of JCAR017 (lisocabtagene maraleucel; liso-cel), an
investigational CAR T cell therapy, in relapsed/refractory aggressive
b-cell non-Hodgkin's lymphoma. In solid tumors, data evaluating the
investigational combination of atezolizumab with ABRAXANE®
(nab-paclitaxel) + carboplatin will offer a first look at the clinical
profile of an immunotherapy/chemotherapy combination in advanced
squamous non-small cell lung cancer patients.

Selected abstracts include*:

Multiple Myeloma

Abstract #8001; Oral; Friday, June 1, 2:57 p.m., E450, Pomalidomide,
Bortezomib, and low-dose dexamethasone (PVd) vs. bortezomib and low-dose
dexamethasone (Vd) in Lenalidomide (LEN)-exposed patients (pts) with
relapsed or refractory multiple myeloma (RRMM): Phase 3 OPTIMISMM Trial
(Richardson)

Abstract #8050; Poster; Monday, June 4, 8:00 a.m., Hall A, Board #59,
Comparative analysis of outcomes in African American (AA) and White (W)
patients (pts) treated with lenalidomide (LEN) or Pomalidomide (POM) for
multiple myeloma (MM) (Ailawadhai)

Lymphoma

Abstract #7500; Oral; Sunday, June 3, 9:45 a.m., E450, Phase III
randomized study of lenalidomide plus rituximab (R2) versus chemotherapy
plus rituximab, followed by rituximab maintenance, in patients with
previously untreated follicular lymphoma (Fowler)

Abstract #7548; Poster; Monday, June 4, 8:00 a.m., Hall A, Board #185,
Results of real-time cell-of-origin subtype identification by gene
expression profiling in patients with ABC-type diffuse large B-cell
lymphoma in the phase III trial of lenalidomide plus R-CHOP vs placebo
plus R-CHOP (ROBUST) (Nowakowski)

Acute Myeloid Leukemia

Abstract #7042; Poster; Monday, June 4, 8:00 a.m., Hall A Board #102,
Mutant IDH (mIDH) inhibitors, ivosidenib or enasidenib, with azacytidine
(AZA) in patients with acute myeloid leukemia (AML) (DiNardo)

CAR T

Abstract #8007; Oral; Friday, June 1, 4:57 p.m., E450, BB2121 anti-BCMA
CAR T cell therapy in patients with relapsed/refractory multiple
myeloma: Updated results from a multicenter Phase 1 study (Raje)

Abstract #7505; Oral; Sunday, June 3, 11:09 a.m., E450, Updated safety &
long term clinical outcomes in TRANSCEND NHL 001, Pivotal trial of
lisocabtagene maraleucel (JCAR017) in R/R aggressive NHL (Abramson)

Abstract #7005; Oral; Saturday, June 2, 4:48 p.m., E450, Factors
impacting disease-free survival in adult B cell B-ALL patients achieving
MRD-negative CR after CD19 CAR-T cells (Hay)

Abstract #8024; Poster; Monday, June 4, 8:00 a.m., Hall A, Board #33,
Early MRD negativity predicts deepening myeloma response in
relapsed/refractory multiple myeloma (RRMM) patients treated with BB2121
anti-BCMA CAR T cells (Munshi)

Squamous Non-Small Cell Lung Cancer

Abstract #LBA9000; Oral Late Breaker; Monday, June 4, 3:00 p.m., Hall
B1, IMpower131: Primary PFS and safety analysis of a randomized phase
III study of atezolizumab + carboplatin + paclitaxel or nab-paclitaxel
vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous NSCLC
(Jotte)

A complete listing of abstracts can be found on the ASCO website at http://abstracts.asco.org.

*All times Central Time

About ABRAXANE®

ABRAXANE® is indicated for the first-line
treatment of locally advanced or metastatic non–small cell lung cancer,
in combination with carboplatin, in patients who are not candidates for
curative surgery or radiation therapy
.

Important Safety Information

 

WARNING - NEUTROPENIA

   

Do not administer ABRAXANE therapy to patients who have
baseline neutrophil counts of less than 1500 cells/mm
3.
In order to monitor the occurrence of bone marrow suppression,
primarily neutropenia, which may be severe and result in
infection, it is recommended that frequent peripheral blood cell
counts be performed on all patients receiving ABRAXANE

 

   

Note: An albumin form of paclitaxel may substantially affect a
drug's functional properties relative to those of drug in
solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL
FORMULATIONS

 

CONTRAINDICATIONS

Neutrophil Counts

  • ABRAXANE should not be used in patients who have baseline neutrophil
    counts of <1500cells/mm3

Hypersensitivity

  • Patients who experience a severe hypersensitivity reaction to ABRAXANE
    should not be rechallenged with the drug

WARNINGS AND PRECAUTIONS

Hematologic Effects

  • Bone marrow suppression (primarily neutropenia) is dose-dependent and
    a dose-limiting toxicity of ABRAXANE. In a clinical study, Grade 3-4
    neutropenia occurred in 47% of patients with non–small cell lung
    cancer (NSCLC)
  • Monitor for myelotoxicity by performing complete blood cell counts
    frequently, including prior to dosing on Days 1, 8, and 15
  • Do not administer ABRAXANE to patients with baseline absolute
    neutrophil counts (ANC) of less than 1500 cells/mm3
  • In the case of severe neutropenia (<500 cells/mm3 for 7
    days or more) during a course of ABRAXANE therapy, reduce the dose of
    ABRAXANE in subsequent courses in patients with NSCLC
  • Resume treatment if recommended at permanently reduced doses for both
    weekly ABRAXANE and every-3-week carboplatin after ANC recovers to at
    least 1500 cells/mm3 and platelet count of at least
    100,000 cells/mm3 on Day 1 or to an ANC of at least 500
    cells/mm3 and platelet count of at least 50,000 cells/mm3
    on Days 8 or 15 of the cycle

Nervous System

  • Sensory neuropathy is dose- and schedule-dependent
  • The occurrence of Grade 1 or 2 sensory neuropathy does not generally
    require dose modification
  • If ≥ Grade 3 sensory neuropathy develops, withhold ABRAXANE treatment
    until resolution to ≤ Grade 1 followed by a dose reduction for all
    subsequent courses of ABRAXANE

Hypersensitivity

  • Severe and sometimes fatal hypersensitivity reactions, including
    anaphylactic reactions, have been reported
  • Patients who experience a severe hypersensitivity reaction to ABRAXANE
    should not be rechallenged with this drug

Hepatic Impairment

  • Because the exposure and toxicity of paclitaxel can be increased with
    hepatic impairment, administration of ABRAXANE in patients with
    hepatic impairment should be performed with caution
  • Patients with hepatic impairment may be at an increased risk of
    toxicity, particularly from myelosuppression, and should be monitored
    for development of profound myelosuppression
  • For NSCLC, the starting dose should be reduced for patients with
    moderate or severe hepatic impairment

Albumin (Human)

  • ABRAXANE contains albumin (human), a derivative of human blood

Use in Pregnancy: Pregnancy Category D

  • ABRAXANE can cause fetal harm when administered to a pregnant woman
  • If this drug is used during pregnancy, or if the patient becomes
    pregnant while receiving this drug, the patient should be apprised of
    the potential hazard to the fetus
  • Women of childbearing potential should be advised to avoid becoming
    pregnant while receiving ABRAXANE

Use in Men

  • Men should be advised not to father a child while receiving ABRAXANE

ADVERSE REACTIONS

Non–Small Cell Lung Cancer (NSCLC) Study

  • The most common adverse reactions (≥20%) of ABRAXANE in combination
    with carboplatin are anemia, neutropenia, thrombocytopenia, alopecia,
    peripheral neuropathy, nausea, and fatigue
  • The most common serious adverse reactions of ABRAXANE in combination
    with carboplatin for NSCLC are anemia (4%) and pneumonia (3%)
  • The most common adverse reactions resulting in permanent
    discontinuation of ABRAXANE are neutropenia (3%), thrombocytopenia
    (3%), and peripheral neuropathy (1%)
  • The most common adverse reactions resulting in dose reduction of
    ABRAXANE are neutropenia (24%), thrombocytopenia (13%), and anemia (6%)
  • The most common adverse reactions leading to withholding or delay in
    ABRAXANE dosing are neutropenia (41%), thrombocytopenia (30%), and
    anemia (16%)
  • The following common (≥10% incidence) adverse reactions were observed
    at a similar incidence in ABRAXANE plus carboplatin–treated and
    paclitaxel injection plus carboplatin–treated patients: alopecia
    (56%), nausea (27%), fatigue (25%), decreased appetite (17%), asthenia
    (16%), constipation (16%), diarrhea (15%), vomiting (12%), dyspnea
    (12%), and rash (10%); incidence rates are for the ABRAXANE plus
    carboplatin treatment group
  • Adverse reactions with a difference of ≥2%, Grade 3 or higher, with
    combination use of ABRAXANE and carboplatin vs combination use of
    paclitaxel injection and carboplatin in NSCLC are anemia (28%, 7%),
    neutropenia (47%, 58%), thrombocytopenia (18%, 9%), and peripheral
    neuropathy (3%, 12%), respectively
  • Adverse reactions with a difference of ≥5%, Grades 1-4, with
    combination use of ABRAXANE and carboplatin vs combination use of
    paclitaxel injection and carboplatin in NSCLC are anemia (98%, 91%),
    thrombocytopenia (68%, 55%), peripheral neuropathy (48%, 64%), edema
    peripheral (10%, 4%), epistaxis (7%, 2%), arthralgia (13%, 25%), and
    myalgia (10%, 19%), respectively
  • Neutropenia (all grades) was reported in 85% of patients who received
    ABRAXANE and carboplatin vs 83% of patients who received paclitaxel
    injection and carboplatin

Postmarketing Experience With ABRAXANE and Other Paclitaxel
Formulations

  • Severe and sometimes fatal hypersensitivity reactions have been
    reported with ABRAXANE. The use of ABRAXANE in patients previously
    exhibiting hypersensitivity to paclitaxel injection or human albumin
    has not been studied
  • There have been reports of congestive heart failure, left ventricular
    dysfunction, and atrioventricular block with ABRAXANE, primarily among
    individuals with underlying cardiac history or prior exposure to
    cardiotoxic drugs
  • There have been reports of extravasation of ABRAXANE. Given the
    possibility of extravasation, it is advisable to monitor closely the
    ABRAXANE infusion site for possible infiltration during drug
    administration

DRUG INTERACTIONS

  • Caution should be exercised when administering ABRAXANE concomitantly
    with medicines known to inhibit or induce either CYP2C8 or CYP3A4

USE IN SPECIFIC POPULATIONS

Nursing Mothers

  • It is not known whether paclitaxel is excreted in human milk. Because
    many drugs are excreted in human milk and because of the potential for
    serious adverse reactions in nursing infants, a decision should be
    made to discontinue nursing or to discontinue the drug, taking into
    account the importance of the drug to the mother

Pediatric

  • The safety and effectiveness of ABRAXANE in pediatric patients have
    not been evaluated

Geriatric

  • Myelosuppression, peripheral neuropathy, and arthralgia were more
    frequent in patients ≥65 years of age treated with ABRAXANE and
    carboplatin in NSCLC

Renal Impairment

  • There are insufficient data to permit dosage recommendations in
    patients with severe renal impairment or end stage renal disease
    (estimated creatinine clearance <30 mL/min)

DOSAGE AND ADMINISTRATION

  • Do not administer ABRAXANE to any patient with total bilirubin greater
    than 5 x ULN or AST greater than 10 x ULN
  • Reduce starting dose in NSCLC patients with moderate to severe hepatic
    impairment
  • Dose reductions or discontinuation may be needed based on severe
    hematologic or neurologic toxicity
  • Monitor patients closely

Please see full Prescribing
Information
, including Boxed WARNING.

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 POMALYST

Indication

POMALYST® (pomalidomide) is a thalidomide analogue indicated,
in combination with dexamethasone, for patients with multiple myeloma
who have received at least two prior therapies including lenalidomide
and a proteasome inhibitor and have demonstrated disease progression on
or within 60 days of completion of the last therapy.

Important Safety Information

 

WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL
THROMBOEMBOLISM

 

Embryo-Fetal Toxicity

  • POMALYST is contraindicated in pregnancy. POMALYST is a
    thalidomide analogue. Thalidomide is a known human teratogen
    that causes severe birth defects or embryo-fetal death. In
    females of reproductive potential, obtain 2 negative pregnancy
    tests before starting POMALYST treatment.
  • Females of reproductive potential must use 2 forms of
    contraception or continuously abstain from heterosexual sex
    during and for 4 weeks after stopping POMALYST treatment.

POMALYST is only available through a restricted distribution
program called POMALYST REMS
®.

 

Venous and Arterial Thromboembolism

  • Deep venous thrombosis (DVT), pulmonary embolism (PE),
    myocardial infarction, and stroke occur in patients with
    multiple myeloma treated with POMALYST. Prophylactic
    antithrombotic measures were employed in clinical trials.
    Thromboprophylaxis is recommended, and the choice of regimen
    should be based on assessment of the patient's underlying risk
    factors.
 

CONTRAINDICATIONS

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

WARNINGS AND PRECAUTIONS

  • Embryo-Fetal Toxicity & Females of
    Reproductive Potential: See Boxed WARNINGS
    • Males: Pomalidomide 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 POMALYST and for up to 4
      weeks after discontinuing POMALYST, even if they have undergone a
      successful vasectomy. Males must not donate sperm.
    • Blood Donation: Patients must not
      donate blood during treatment with POMALYST and for 4 weeks
      following discontinuation of POMALYST therapy because the blood
      might be given to a pregnant female patient whose fetus must not
      be exposed to POMALYST.
  • POMALYST REMS®
    Program: See Boxed WARNINGS
    • Prescribers and pharmacies must be certified with the POMALYST
      REMS
      program by enrolling and complying with the REMS
      requirements; pharmacies must only dispense to patients who are
      authorized to receive POMALYST. 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.
    • Further information about the POMALYST REMS program is
      available at www.CelgeneRiskManagement.com
      or by telephone at 1-888-423-5436.
  • Venous and Arterial Thromboembolism: See
    Boxed WARNINGS.
    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
    choice of regimen should be based on assessment of the patient's
    underlying risk factors.
  • 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.
  • Hematologic Toxicity:
    Neutropenia (46%) was the most frequently reported Grade 3/4 adverse
    reaction in patients taking POMALYST in clinical trials, followed by
    anemia and thrombocytopenia. Monitor complete blood counts weekly for
    the first 8 weeks and monthly thereafter. Patients may require dose
    interruption and/or modification.
  • Hepatotoxicity: Hepatic
    failure, including fatal cases, has occurred in patients treated with
    POMALYST. Elevated levels of alanine aminotransferase and bilirubin
    have also been observed in patients treated with POMALYST. Monitor
    liver function tests monthly. Stop POMALYST 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. Discontinue POMALYST for angioedema, skin
    exfoliation, bullae, or any other severe cutaneous reactions such as
    SJS, TEN or DRESS, and do not resume therapy.
  • Dizziness and Confusional State:
    In patients taking POMALYST in clinical trials, 14% experienced
    dizziness (1% Grade 3 or 4) and 7% a confusional state (3% Grade 3 or
    4). Instruct patients to avoid situations where dizziness or
    confusional state may be a problem and not to take other medications
    that may cause dizziness or confusional state without adequate medical
    advice.
  • Neuropathy: In patients
    taking POMALYST in clinical trials, 18% experienced neuropathy (2%
    Grade 3 in one trial) and 12% peripheral neuropathy.
  • Second Primary Malignancies: Cases
    of acute myelogenous leukemia have been reported in patients receiving
    POMALYST as an investigational therapy outside of multiple myeloma.
  • Tumor Lysis Syndrome (TLS): TLS
    may occur in patients treated with POMALYST. Patients at risk are
    those with high tumor burden prior to treatment. These patients should
    be monitored closely and appropriate precautions taken.

ADVERSE REACTIONS

The most common adverse reactions for POMALYST (≥30%) included fatigue
and asthenia, neutropenia, anemia, constipation, nausea, diarrhea,
dyspnea, upper-respiratory tract infections, back pain, and pyrexia.

In the phase III trial, nearly all patients treated with POMALYST +
low-dose dex experienced at least one adverse reaction (99%). Adverse
reactions (≥15% in the POMALYST + low-dose dex arm and ≥2% higher than
control) included neutropenia (51.3%), fatigue and asthenia (46.7%),
upper respiratory tract infection (31%), thrombocytopenia (29.7%),
pyrexia (26.7%), dyspnea (25.3%), diarrhea (22%), constipation (21.7%),
back pain (19.7%), cough (20%), pneumonia (19.3%), bone pain (18%),
edema peripheral (17.3%), peripheral neuropathy (17.3%), muscle spasms
(15.3%), and nausea (15%). Grade 3 or 4 adverse reactions (≥15% in the
POMALYST + low-dose dex arm and ≥1% higher than control) included
neutropenia (48.3%), thrombocytopenia (22%), and pneumonia (15.7%).

DRUG INTERACTIONS

Avoid concomitant use of POMALYST with strong inhibitors of CYP1A2.
Consider alternative treatments. If a strong CYP1A2 inhibitor must be
used, reduce POMALYST dose by 50%.

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 POMALYST pregnancy exposure registry that monitors pregnancy
    outcomes in females exposed to POMALYST during pregnancy as well as
    female partners of male patients who are exposed to POMALYST. This
    registry is also used to understand the root cause for the pregnancy.
    Report any suspected fetal exposure to POMALYST 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 pomalidomide in human milk, the
    effects of POMALYST on the breastfed child, or the effects of POMALYST
    on milk production. Pomalidomide was excreted in the milk of lactating
    rats. Because many drugs are excreted in human milk and because of the
    potential for adverse reactions in a breastfed child from POMALYST,
    advise women not to breastfeed during treatment with POMALYST.
  • Pediatric Use: Safety and
    effectiveness have not been established in pediatric patients.
  • Geriatric Use: No dosage
    adjustment is required for POMALYST based on age. Patients >65 years
    of age were more likely than patients ≤65 years of age to experience
    pneumonia.
  • Renal Impairment: Reduce
    POMALYST dose by 25% in patients with severe renal impairment
    requiring dialysis. Take dose of POMALYST following hemodialysis on
    hemodialysis days.
  • Hepatic Impairment: Reduce
    POMALYST dose by 25% in patients with mild to moderate hepatic
    impairment and 50% in patients with severe hepatic impairment.
  • Smoking Tobacco: Advise
    patients that smoking may reduce the efficacy of POMALYST. Cigarette
    smoking reduces the AUC of pomalidomide by 32% by CYP1A2 induction.

Please see full Prescribing
Information
, including Boxed WARNINGS.

About Celgene's Immunomodulatory Drugs

Immunomodulatory Drugs (IMiDs®) are Celgene's proprietary small
molecule, orally available compounds for the treatment of some blood
cancers. IMiDs® are the foundation of multiple myeloma treatment, driven
by the proven survival benefits across lines of therapy. Their mechanism
of action is well defined and offers the combination of striking tumor
cells, stimulating the immune system, and synergizing with other classes
of treatment. With REVLIMID® (lenalidomide) and POMALYST®/IMNOVID®
(pomalidomide), Celgene has a portfolio of innovative medicines that
have helped transform the treatment of multiple myeloma, providing
patients longer disease control at every stage of the disease from newly
diagnosed to relapse refractory multiple myeloma.

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.
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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. Celgene undertakes 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's Annual Report on Form 10-K and other reports filed with the
Securities and Exchange Commission.

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