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Broad Range of Clinical Data Evaluating Celgene Therapies to Be Presented at American Society of Clinical Oncology (ASCO)

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Celgene Corporation (NASDAQ:CELG) today announced that data from a
broad range of company-sponsored and investigator-initiated studies
evaluating Celgene investigational agents and investigational uses of
marketed products will be presented at the American Society of Clinical
Oncology Annual Meeting between June 2-6 in Chicago, Ill.

"We are part of an extremely exciting time in cancer research, where
accelerating deep insights into the biology of disease and tumor
microenvironment are leading to approaches that have the potential to
make a major impact on patients' lives," said Michael Pehl, President,
Hematology and Oncology for Celgene. "The studies being shared at ASCO
this year reinforce our commitment to developing and delivering
innovative treatment options to patients with cancer around the world."

In multiple myeloma, abstracts will continue to support the role of
Celgene's IMiD® therapies as the foundation of multiple
myeloma research, including in the maintenance setting. Additionally,
data will be presented from the study evaluating the investigational R2
regimen (REVLIMID® (lenalidomide) and rituximab combination),
in previously-treated follicular lymphoma. Updated data from two studies
in the ABOUND program evaluating ABRAXANE® (nab-paclitaxel)
in non-small cell lung cancer will also be presented. Finally, results
from multiple studies highlighting key Celgene research collaborations
of investigational compounds will be presented, including updated data
from a phase I dose escalation and expansion study of IDHIFA®
(enasidenib) in patients with mutant-IDH2 relapsed/refractory acute
myeloid leukemia, updated data from the first clinical study of
anti-BCMA CAR-T therapy bb2121 in multiple myeloma, and results from a
study of CAR-T therapy JCAR017 in previously-treated aggressive b-cell
non-Hodgkin's lymphoma.

Selected abstracts include*:

Newly-diagnosed Multiple Myeloma

Abstract #8000; Oral; Sunday, June 4, 9:45 a.m., E354b, Daratumumab
(DARA) in combination with carfilzomib, lenalidomide, and dexamethasone
(KRd) in patients (pts) with newly diagnosed multiple myeloma (MMY1001):
An open-label, phase Ib study (Jakubowiak)

Abstract #8001; Oral; Sunday, June 4, 9:57 a.m., E354b, Lenalidomide,
adriamycin and dexamethasone versus bortezomib, lenalidomide and
dexamethasone prior to scheduled stem cell transplant in newly diagnosed
multiple myeloma (Knop)

Abstract #8002; Oral; Sunday, June 4, 10:09 a.m., E354b, An open-label,
single arm, phase IIa study of bortezomib, lenalidomide, dexamethasone,
and elotuzumab in newly diagnosed multiple myeloma (Laubach)

Abstract #8009; Poster Discussion; Monday, June 5, 3:00 p.m., E354b,
Lenalidomide induction and maintenance therapy for myeloma: Results of
the Myeloma XI Study (Jackson)

Abstract #8023; Poster; Monday, June 5, 8:00 a.m., Hall A, Impact of
t(11;14) on outcomes in African American (AA) and non-AA (NAA) patients
(Pts) with newly diagnosed multiple myeloma (NDMM): Connect®
MM Registry (Gasparetto)

Relapsed/Refractory Multiple Myeloma

Abstract #8007; Oral; Sunday, June 4, 11:57 a.m., E354b, A phase Ib
study of isatuximab in combination with pomalidomide (Pom) and
dexamethasone (Dex) in relapsed/refractory multiple myeloma (RRMM)
(Mikhael)

Abstract #8008; Oral; Sunday, June 4, 12:09 p.m., E354b, Phase I/II dose
expansion of a trial investigating bendamustine and pomalidomide with
dexamethasone (Ben-Pom-d) in patients with relapsed/refractory multiple
myeloma (Sivaraj)

Abstract #8015; Poster Discussion; Monday, June 5, 3:00 p.m., E354b,
Pembrolizumab (Pembro) plus lenalidomide (Len) and low-dose
dexamethasone (Dex) for relapsed/refractory multiple myeloma (RRMM):
Efficacy and biomarker analyses (Ocio)

Abstract #3010; Poster Discussion; Monday, June 5, 4:45 p.m., Hall D1,
First-in-human multicenter study of bb2121 anti-BCMA CAR T-cell therapy
for relapsed/refractory multiple myeloma: Updated results (Berdeja)

Abstract #8027; Poster; Monday, June 5, 8:00 a.m., Hall A, Phase II
study of pomalidomide (POM) + low-dose dexamethasone (LoDEX) following
second-line lenalidomide (LEN)-based treatment (Tx) in patients (Pts)
with relapsed or refractory multiple myeloma (RRMM): An updated analysis
of efficacy and safety (Siegel)

Maintenance in Multiple Myeloma

Abstract #8037; Poster; Monday, June 5, 8:00 a.m., Hall A, CALGB/ECOG
100104 (Alliance) study: Lenalidomide (LEN) vs placebo (PBO) maintenance
(Maint) after stem cell transplant (SCT) for patients (Pts) with
multiple myeloma: Overall survival (OS) and progression-free survival
(PFS) adjusted for treatment (Tx) crossover (XO) (McCarthy)

Abstract #8040; Poster; Monday, June 5, 8:00 a.m., Hall A, Impact of
post-autologous stem cell transplant (ASCT) maintenance therapy on
outcomes in patients (Pts) with newly diagnosed multiple myeloma (NDMM)
using the large prospective community-based Connect® MM
Registry (Jagannath)

Acute Myeloid Leukemia

Abstract #7004; Oral; Tuesday, June 6, 10:57 a.m., E450ab, Enasidenib in
mutant-IDH2 relapsed or refractory acute myeloid leukemia (R/R AML):
Results of a phase I dose-escalation and expansion study (Stein)

Abstract #7015; Poster Discussion; Monday, June 5, 11:30 a.m., E354b,
Differentiation syndrome associated with enasidenib, a selective
inhibitor of mutant isocitrate dehydrogenase 2 (IDH2) (Fathi)

Abstract #7022; Poster; Monday, June 5, 8:00 a.m., Hall A, Molecular
genetic testing patterns for patients with newly diagnosed acute myeloid
leukemia (AML) enrolled in the CONNECT® MDS/AML Disease
Registry (Pollyea)

Lymphoma/CLL

Abstract #7502; Oral; Saturday, June 3, 3:24 p.m., S100bc, Phase IIIb
randomized study of lenalidomide plus rituximab (R2) followed by
maintenance in relapsed/refractory NHL: Analysis of patients with
double-refractory or early relapsed follicular lymphoma (FL) (Andorsky)

Abstract #7503; Oral; Saturday, June 3, 4:00 p.m., S100bc, A genetic
risk-stratified, phase II study of fludarabine/antibody combinations in
symptomatic, untreated chronic lymphocytic leukemia (CLL): Final results
of Cancer and Leukemia Group B (CALGB) 10404 (Ruppert)

Abstract #7513; Poster Discussion; Monday, June 5, 1:15 p.m., E354b, CR
rates in relapsed/refractory (R/R) aggressive B-NHL treated with the
CD19-directed CAR T-cell product JCAR017 (TRANSCEND NHL 001) (Abramson)

Non-Small Cell Lung Cancer

Abstract #9058; Poster; Saturday, June 3, 8:00 a.m., Hall A, Safety and
efficacy of nab-paclitaxel (nab-P)–based therapy in patients (pts) with
non-small cell lung cancer (NSCLC) and performance status (PS) 2:
Results from ABOUND.PS2 (Gajra)

Abstract #9059; Poster; Saturday, June 3, 8:00 a.m., Hall A, ABOUND.70+:
Safety and efficacy of nab-paclitaxel/carboplatin (nab-P/C) in elderly
patients (pts) with advanced non-small cell lung cancer (NSCLC) (Langer)

Abstract #9092; Poster; Saturday, June 3, 8:00 a.m., Hall A,
Atezolizumab (atezo) plus platinum-based chemotherapy (chemo) in
non-small cell lung cancer (NSCLC): Update from a phase Ib study (Liu)

Abstract #9095; Poster; Saturday, June 3, 8:00 a.m., Hall A, Nivolumab
(nivo) + nab-paclitaxel (nab-P) + carboplatin (C) in patients (pts) with
non-small cell lung cancer (NSCLC): Interim results from a multicenter
phase I study (Waterhouse)

Biliary Tract Cancer

Abstract #9095; Poster; Saturday, June 3, 8:00 a.m., Hall A, A phase II
trial of gemcitabine (G), cisplatin (C), and nab-paclitaxel (N) in
advanced biliary tract cancers (aBTCs) (Shroff)

The safety and efficacy of the agents and/or uses under investigation
have not been established. There is no guarantee that the agents will
receive health authority approval or become commercially available in
any country for the uses being investigated.

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

*All times Central Time

About ABRAXANE®

ABRAXANE® for Injectable Suspension
(paclitaxel protein-bound particles for injectable suspension)
(albumin-bound) is indicated for the treatment of breast cancer after
failure of combination chemotherapy for metastatic disease or relapse
within 6 months of adjuvant chemotherapy. Prior therapy should have
included an anthracycline unless clinically contraindicated.

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.

ABRAXANE is indicated for the first-line treatment of patients with
metastatic adenocarcinoma of the pancreas, in combination with
gemcitabine.

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 <1500 cells/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 clinical studies, Grade 3-4
    neutropenia occurred in 34% of patients with metastatic breast cancer
    (MBC), 47% of patients with non–small cell lung cancer (NSCLC), and
    38% of patients with pancreatic cancer
  • Monitor for myelotoxicity by performing complete blood cell counts
    frequently, including prior to dosing on Day 1 (for MBC) and Days 1,
    8, and 15 (for NSCLC and for pancreatic cancer)
  • 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 either MBC or NSCLC
  • In patients with MBC, resume treatment with every-3-week cycles of
    ABRAXANE after ANC recovers to a level >1500 cells/mm3
    and platelets recover to a level >100,000 cells/mm3
  • 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
  • In patients with adenocarcinoma of the pancreas, withhold ABRAXANE and
    gemcitabine if the ANC is less than 500 cells/mm3 or
    platelets are less than 50,000 cells/mm3 and delay
    initiation of the next cycle if the ANC is less than 1500 cells/mm3
    or platelet count is less than 100,000 cells/mm3 on Day 1
    of the cycle. Resume treatment with appropriate dose reduction if
    recommended

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 or 2 for MBC or until resolution to
    ≤ Grade 1 for NSCLC and pancreatic cancer followed by a dose reduction
    for all subsequent courses of ABRAXANE

Sepsis

  • Sepsis occurred in 5% of patients with or without neutropenia who
    received ABRAXANE in combination with gemcitabine
  • Biliary obstruction or presence of biliary stent were risk factors for
    severe or fatal sepsis
  • If a patient becomes febrile (regardless of ANC), initiate treatment
    with broad-spectrum antibiotics
  • For febrile neutropenia, interrupt ABRAXANE and gemcitabine until
    fever resolves and ANC ≥1500 cells/mm3, then resume
    treatment at reduced dose levels

Pneumonitis

  • Pneumonitis, including some cases that were fatal, occurred in 4% of
    patients receiving ABRAXANE in combination with gemcitabine
  • Monitor patients for signs and symptoms and interrupt ABRAXANE and
    gemcitabine during evaluation of suspected pneumonitis
  • Permanently discontinue treatment with ABRAXANE and gemcitabine upon
    making a diagnosis of pneumonitis

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 MBC and NSCLC, the starting dose should be reduced for patients
    with moderate or severe hepatic impairment
  • For pancreatic adenocarcinoma, ABRAXANE is not recommended for
    patients with moderate to severe hepatic impairment (total bilirubin
    >1.5 x ULN and AST ≤10 x ULN)

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

Randomized Metastatic Breast Cancer (MBC) Study

  • The most common adverse reactions (≥20%) with single-agent use of
    ABRAXANE vs paclitaxel injection in the MBC study are alopecia (90%,
    94%), neutropenia (all cases 80%, 82%; severe 9%, 22%), sensory
    neuropathy (any symptoms 71%, 56%; severe 10%, 2%), abnormal ECG (all
    patients 60%, 52%; patients with normal baseline 35%, 30%),
    fatigue/asthenia (any 47%, 39%; severe 8%, 3%), myalgia/arthralgia
    (any 44%, 49%; severe 8%, 4%), AST elevation (any 39%, 32%), alkaline
    phosphatase elevation (any 36%, 31%), anemia (any 33%, 25%; severe 1%,
    <1%), nausea (any 30%, 22%; severe 3%, <1%), diarrhea (any 27%, 15%;
    severe <1%, 1%) and infections (24%, 20%), respectively
  • Sensory neuropathy was the cause of ABRAXANE discontinuation in 7/229
    (3%) patients
  • Other adverse reactions of note with the use of ABRAXANE vs paclitaxel
    injection included vomiting (any 18%, 10%; severe 4%, 1%), fluid
    retention (any 10%, 8%; severe 0%, <1%), mucositis (any 7%, 6%; severe
    <1%, 0%), hepatic dysfunction (elevations in bilirubin 7%, 7%),
    hypersensitivity reactions (any 4%, 12%; severe 0%, 2%),
    thrombocytopenia (any 2%, 3%; severe <1%, <1%), neutropenic sepsis
    (<1%, <1%), and injection site reactions (<1%, 1%), respectively.
    Dehydration and pyrexia were also reported
  • Renal dysfunction (any 11%, severe 1%) was reported in patients
    treated with ABRAXANE (n=229)
  • In all ABRAXANE-treated patients (n=366), ocular/visual disturbances
    were reported (any 13%; severe 1%)
  • Severe cardiovascular events possibly related to single-agent ABRAXANE
    occurred in approximately 3% of patients and included cardiac
    ischemia/infarction, chest pain, cardiac arrest, supraventricular
    tachycardia, edema, thrombosis, pulmonary thromboembolism, pulmonary
    emboli, and hypertension
  • Cases of cerebrovascular attacks (strokes) and transient ischemic
    attacks have been reported

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

Pancreatic Adenocarcinoma Study

  • Among the most common (≥20%) adverse reactions in the phase III study,
    those with a ≥5% higher incidence in the ABRAXANE/gemcitabine group
    compared with the gemcitabine group are neutropenia (73%, 58%),
    fatigue (59%, 46%), peripheral neuropathy (54%, 13%), nausea (54%,
    48%), alopecia (50%, 5%), peripheral edema (46%, 30%), diarrhea (44%,
    24%), pyrexia (41%, 28%), vomiting (36%, 28%), decreased appetite
    (36%, 26%), rash (30%, 11%), and dehydration (21%, 11%)
  • Of these most common adverse reactions, those with a ≥2% higher
    incidence of Grade 3-4 toxicity in the ABRAXANE/gemcitabine group
    compared with the gemcitabine group, respectively, are neutropenia
    (38%, 27%), fatigue (18%, 9%), peripheral neuropathy (17%, 1%), nausea
    (6%, 3%), diarrhea (6%, 1%), pyrexia (3%, 1%), vomiting (6%, 4%),
    decreased appetite (5%, 2%), and dehydration (7%, 2%)
  • Thrombocytopenia (all grades) was reported in 74% of patients in the
    ABRAXANE/gemcitabine group vs 70% of patients in the gemcitabine group
  • The most common serious adverse reactions of ABRAXANE (with a ≥1%
    higher incidence) are pyrexia (6%), dehydration (5%), pneumonia (4%),
    and vomiting (4%)
  • The most common adverse reactions resulting in permanent
    discontinuation of ABRAXANE were peripheral neuropathy (8%), fatigue
    (4%), and thrombocytopenia (2%)
  • The most common adverse reactions resulting in dose reduction of
    ABRAXANE are neutropenia (10%) and peripheral neuropathy (6%)
  • The most common adverse reactions leading to withholding or delay in
    ABRAXANE dosing are neutropenia (16%), thrombocytopenia (12%), fatigue
    (8%), peripheral neuropathy (15%), anemia (5%), and diarrhea (5%)
  • Other selected adverse reactions with a ≥5% higher incidence for
    all-grade toxicity in the ABRAXANE/gemcitabine group compared to the
    gemcitabine group, respectively, are asthenia (19%, 13%), mucositis
    (10%, 4%), dysgeusia (16%, 8%), headache (14%, 9%), hypokalemia (12%,
    7%), cough (17%, 7%), epistaxis (15%, 3%), urinary tract infection
    (11%, 5%), pain in extremity (11%, 6%), arthralgia (11%, 3%), myalgia
    (10%, 4%), and depression (12%, 6%)
  • Other selected adverse reactions with a ≥2% higher incidence for Grade
    3-4 toxicity in the ABRAXANE/gemcitabine group compared to the
    gemcitabine group are thrombocytopenia (13%, 9%), asthenia (7%, 4%),
    and hypokalemia (4%, 1%)

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

  • A higher incidence of epistaxis, diarrhea, dehydration, fatigue, and
    peripheral edema was found in patients 65 years or older who received
    ABRAXANE for MBC in a pooled analysis of clinical studies
  • Myelosuppression, peripheral neuropathy, and arthralgia were more
    frequent in patients ≥65 years of age treated with ABRAXANE and
    carboplatin in NSCLC
  • Diarrhea, decreased appetite, dehydration, and epistaxis were more
    frequent in patients 65 years or older compared with patients younger
    than 65 years old who received ABRAXANE and gemcitabine in
    adenocarcinoma of the pancreas

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
  • For MBC and NSCLC, reduce starting dose in patients with moderate to
    severe hepatic impairment
  • For adenocarcinoma of the pancreas, do not administer ABRAXANE to
    patients who have moderate to severe hepatic impairment
  • Dose reductions or discontinuation may be needed based on severe
    hematologic, neurologic, cutaneous, or gastrointestinal 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

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: 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 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

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

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 treatment should be evaluated in patients with lactose
intolerance

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

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 for patients on dialysis

Please see full Prescribing
Information
, including Boxed WARNINGS.

About POMALYST®

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 1 month
      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.
  • 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.
  • Hypersensitivity Reactions: Angioedema
    and severe dermatologic reactions have been reported. Discontinue
    POMALYST for angioedema, skin exfoliation, bullae, or any other severe
    dermatologic reactions, 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

Nearly all patients treated with POMALYST + low-dose dex experienced at
least one adverse reaction (99%). The most common adverse reactions
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 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 infant, 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 breastfed infants
    from POMALYST, advise a nursing woman to discontinue breastfeeding
    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

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: @CelgenePinterestLinkedInFacebook 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. 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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