Market Overview

Results from 282 Abstracts Including Celgene Therapies and Pipeline Compounds to Be Presented at the American Society of Hematology Annual Meeting (ASH)

Share:

Presentations will focus on a wide range of disease areas including
multiple myeloma, lymphoma, acute myeloid leukemia, myelodysplastic
syndromes and beta-thalassemia and novel technologies such as CAR-T cell
therapy

Celgene Corporation (NASDAQ:CELG) today announced that data from 282
abstracts, including more than 60 oral presentations, evaluating Celgene
investigational agents and investigational uses of marketed products
will be presented at the 59th American Society of Hematology
Annual Meeting between Dec. 9-12 in Atlanta, GA.

Presentations will include investigational data from Celgene agents in
company-sponsored or investigator-initiated studies.

"Disease altering advances in hematology are coming at a more rapid pace
than ever and we are looking forward to new insights into the treatment
of deadly blood cancers and other serious diseases," said Nadim Ahmed,
President, Hematology and Oncology for Celgene. "Presentations
highlighting data from more than 150 studies in multiple myeloma
utilizing the foundation of IMiD® therapies in
investigational uses continue to grow the body of evidence for these
treatments. We are also excited about results from novel technologies
such as CAR-T cell therapy and other pipeline candidates across multiple
disease areas that demonstrate our commitment to patients with
life-threatening hematologic diseases."

Selected abstracts include*:

Multiple Myeloma

Data will be presented from the immunotherapy-focused collaboration
between Celgene and bluebird bio demonstrating significant potential in
multiple myeloma research:

Abstract #740; Oral; Monday, Dec. 11. 3 p.m., Hall C1, Durable clinical
responses in heavily pretreated patients with relapsed/refractory
multiple myeloma: Updated results from a multicenter study of bb2121
anti-BCMA CAR T cell therapy (Kochenderfer)

Among the more than 150 studies including IMiD-based regimens, including
investigational combinations, there are presentations across the myeloma
continuum. Some of these include:

Abstract #1811; Poster; Saturday, Dec. 9, 5:30 p.m., Hall A2, Safety and
Efficacy of Pomalidomide (POM) + Low-Dose Dexamethasone (LoDEX) +
Daratumumab (DARA) As Second- or Third-Line Therapy in Patients with
Relapsed and/or Refractory Multiple Myeloma (RRMM) after Lenalidomide
(LEN)-Based Treatment (Tx) Failure (Siegel)

Abstract #400; Oral; Sunday, Dec. 10, 10:15 a.m., C101, Response-Adapted
Lenalidomide Maintenance in Newly Diagnosed, Transplant-Eligible
Multiple Myeloma: Results from the Multicenter Phase III GMMG-MM5 Trial
(Goldschmidt)

Abstract #402; Oral; Sunday, Dec. 10, 10:45 a.m., C101, Curative
Strategy for High-Risk Smoldering Myeloma (GEM-CESAR): Carfilzomib,
Lenalidomide and Dexamethasone (KRd) As Induction Followed By HDT-ASCT,
Consolidation with Krd and Maintenance with Rd (Mateos)

Abstract #436; Oral; Sunday, Dec. 10, 12:45 p.m., Hall C4, Lenalidomide
maintenance significantly improves outcomes compared to observation
irrespective of cytogenetic risk: Results of the Myeloma XI trial
(Jackson)

Abstract #739; Oral; Monday, Dec. 11, 2:45 p.m., Hall C1, Daratumumab,
Lenalidomide, and Dexamethasone (DRd) Versus Lenalidomide and
Dexamethasone (Rd) in Relapsed or Refractory Multiple Myeloma (RRMM):
Updated Efficacy and Safety Analysis of Pollux (Dimopoulos)

Abstract #743; Oral; Monday, Dec. 11, 3:45 p.m., Hall C1, Overall
Survival (OS) of Patients with Relapsed/Refractory Multiple Myeloma
(RRMM) Treated with Carfilzomib, Lenalidomide, and Dexamethasone (KRd)
Versus Lenalidomide and Dexamethasone (Rd): Final Analysis from the
Randomized Phase 3 Aspire Trial (Stewart)

Abstract #837; Oral; Monday, Dec. 11 5 p.m., Hall C1, A Multicenter Open
Label Phase II Study of Pomalidomide, Cyclophosphamide and Dexamethasone
in Relapse Multiple Myeloma Patients Initially Treated with
Lenalidomide, Bortezomib and Dexamethasone (Garderet)

Abstract #904; Oral; Monday, Dec. 11, 7 p.m., Hall C4, Minimal Residual
Disease in the Maintenance Setting in Myeloma: Prognostic Significance
and Impact of Lenalidomide (de Tute)

Abstract #905; Oral; Monday, Dec. 11, 7:15 p.m., Hall C4, Impact of
Next-Generation Flow (NGF) Minimal Residual Disease (MRD) Monitoring in
Multiple Myeloma (MM): Results from the Pethema/GEM2012 Trial (Paiva)

Lymphomas/Chronic Lymphocytic Leukemia (CLL)

Updated data from the CAR-T program JCAR-017 in partnership with Juno
Therapeutics will be presented in multiple studies:

Abstract #193; Oral; Saturday, Dec. 9, 2 p.m., C101, Auditorium Patient
Characteristics and Pre-Infusion Biomarkers of Inflammation Correlate
with Clinical Outcomes after Treatment with the Defined Composition,
CD19-Targeted CAR T Cell Product, JCAR017 (Siddiqi)

Abstract #194; Oral; Saturday, Dec. 9, 2:15 p.m., C101, Auditorium
Predicting Clinical Response and Safety of JCAR017 in B-NHL Patients:
Potential Importance of Tumor Microenvironment Biomarkers and CAR T-Cell
Tumor Infiltration (Swanson)

Abstract #581; Oral; Monday, Dec. 11, 8 a.m., A411-A412, High Durable CR
Rates in Relapsed/Refractory (R/R) Aggressive B-NHL Treated with JCAR017
(TRANSCEND NHL 001): Defined Composition CD19-Directed CAR T Cell
Product Allows for Dose Finding and Definition of Pivotal Cohort
(Abramson)

Several studies presented focus on investigational chemotherapy-free
treatment approaches in indolent lymphoma and CLL, including R2 (REVLIMID®
+ rituximab), while further data from Celgene's pipeline demonstrates
our commitment to new lymphoma research.

Abstract #154; Oral; Saturday, Dec. 9, 12:45 p.m., A411-A412, Initial
Treatment with Lenalidomide Plus Rituximab for Mantle Cell Lymphoma:
5-year Follow-up and Correlative Analysis from a Multi-center Phase II
Study (Ruan)

Abstract #192; Oral; Saturday, Dec. 9, 3:15 p.m., A411-A412, A Phase I,
Open–Label, Multicenter Trial of Oral Azacitidine (CC-486) Plus R–CHOP
in Patients with High-Risk, Previously Untreated Diffuse Large B-Cell
Lymphoma, Grade 3B Follicular Lymphoma, or Transformed Lymphoma (Martin)

Abstract #411; Oral; Sunday, Dec. 10, 12:30 p.m., Hall C1, CC-122, a
Novel Cereblon Modulating Agent, in Combination with Obinutuzumab
(GA101) in Patients with Relapsed and Refractory (R/R) B–cell
Non–Hodgkin Lymphoma (NHL) (Michot)

Abstract #482; Oral; Sunday, Dec. 10, 4:45 p.m., Hall C1, A 3-Arm
Randomized Phase II Trial with Bendamustine/Rituximab Therapy in
Untreated High Risk (HR) Follicular Lymphoma (FL): Bortezomib Induction
or Novel IMiD Continuation (BIONIC) Study from the ECOG-ACRIN Cancer
Research Group (Evens)

Abstract #729; Oral; Monday, Dec. 11, 3:15 p.m., C101 Auditorium,
Lenalidomide Treatment Restores In Vivo T Cell Activity in
Relapsed/Refractory FL and DLBCL (Menard)

Myeloid Diseases

In acute myeloid leukemia (AML), new data for investigational uses of
IDHIFA® (enasidenib) in patients in the relapsed/refractory
and front-line settings in combinations, as well as new phase II data
for CC486 in post-transplant maintenance for AML and in patients with
MDS will be presented.

Abstract #1299; Poster; Saturday, Dec. 9, 5:30 p.m., Hall A2, Continuing
Enasidenib Treatment for Patients with Mutant-IDH2 (mIDH2) Relapsed or
Refractory Acute Myeloid Leukemia (R/R AML) with Stable Disease May
Result in Improved Survival and Responses over Time (Stein)

Abstract #638; Oral; Monday, Dec. 11, 10:45 a.m., Murphy Ballroom 1-2,
Enasidenib Monotherapy Is Effective and Well-tolerated in Patients with
Previously Untreated Mutant-IDH2 (mIDH2) Acute Myeloid Leukemia (AML)
(Pollyea)

Abstract #639; Oral; Monday, Dec. 11, 11 a.m., Murphy Ballroom 1-2,
Mutant Isocitrate Dehydrogenase (mIDH) Inhibitors, Enasidenib or
Ivosidenib, in Combination with Azacitidine (AZA): Preliminary Results
of a Phase 1b/2 Study in Patients with mIDH Newly Diagnosed Acute
Myeloid Leukemia (AML) (DiNardo)

Abstract #726; Oral; Monday, Dec. 11, 4 p.m., Murphy Ballroom 1-2, A
phase 1 trial of ivosidenib and enasidenib combined with standard
induction chemotherapy in newly diagnosed AML patients with an IDH1
and/or IDH2 mutation (Stein)

Abstract #751; Oral; Monday, Dec. 11, 2:45 p.m., C211-C213, Quality of
Life in Patients with β-Thalassemia: Transfusion Dependent Versus
Non-Transfusion Dependent (Cappellini)

Abstract #4512; Poster; Monday, Dec. 11, 6 p.m., Hall A2, Final Analysis
of the Phase I/II Study of CC-486 (Oral Azacitidine) Maintenance Therapy
after Allogeneic Stem Cell Transplantation (Allo-SCT) in Patients with
Acute Myeloid Leukemia (AML) or Myelodysplastic Syndromes (MDS) (de Lima)

The safety and efficacy of investigational agents and/or investigational
uses of approved marketed products 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 ASH Web site at http://www.hematology.org/Annual-Meeting/Abstracts/

*All times Eastern Standard Time

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/IMNOVID

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 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 IDHIFA

IDHIFA (enasidenib) is indicated for the treatment of adult patients
with relapsed or refractory acute myeloid leukemia with an isocitrate
dehydrogenase-2 mutation as detected by an FDA-approved test.

Important Safety Information

WARNING: DIFFERENTIATION SYNDROME

Patients treated with IDHIFA have experienced symptoms of
differentiation syndrome, which can be fatal if not treated. Symptoms
may include fever, dyspnea, acute respiratory distress, pulmonary
infiltrates, pleural or pericardial effusions, rapid weight gain or
peripheral edema, lymphadenopathy, bone pain, and hepatic, renal, or
multi-organ dysfunction. If differentiation syndrome is suspected,
initiate corticosteroid therapy and hemodynamic monitoring until symptom
resolution.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome: See Boxed WARNING. In the clinical
trial, 14% of patients treated with IDHIFA experienced differentiation
syndrome. Differentiation syndrome has been observed with and without
concomitant hyperleukocytosis, as early as 10 days and at up to 5 months
after IDHIFA initiation. If differentiation syndrome is suspected,
initiate systemic corticosteroids and hemodynamic monitoring until
improvement. Taper corticosteroids only after resolution of symptoms.
Differentiation syndrome symptoms may recur with premature
discontinuation of corticosteroids. If severe pulmonary symptoms
requiring intubation or ventilator support and/or renal dysfunction
persist for more than 48 hours after initiation of corticosteroids,
interrupt IDHIFA until signs and symptoms are no longer severe.
Hospitalization for close observation and monitoring of patients with
pulmonary and/or renal manifestation is recommended.

Embryo-Fetal Toxicity: Based on animal embryo-fetal
toxicity studies, IDHIFA can cause embryo-fetal harm when administered
to a pregnant woman. Advise females of reproductive potential and males
with female partners of reproductive potential to use effective
contraception during treatment with IDHIFA and for at least 1 month
after the last dose. Pregnant women, patients becoming pregnant while
receiving IDHIFA, or male patients with pregnant female partners should
be apprised of the potential risk to the fetus.

ADVERSE REACTIONS

  • The most common adverse reactions (≥20%) included total bilirubin
    increased (81%), calcium decreased (74%), nausea (50%), diarrhea
    (43%), potassium decreased (41%), vomiting (34%), decreased appetite
    (34%), and phosphorus decreased (27%)
  • The most frequently reported ≥Grade 3 adverse reactions (≥5%) included
    total bilirubin increased (15%), potassium decreased (15%), phosphorus
    decreased (8%), calcium decreased (8%), diarrhea (8%), differentiation
    syndrome (7%), non-infectious leukocytosis (6%), tumor lysis syndrome
    (6%), and nausea (5%)
  • Serious adverse reactions were reported in 77.1% of patients. The most
    frequent serious adverse reactions (≥2%) were leukocytosis (10%),
    diarrhea (6%), nausea (5%), vomiting (3%), decreased appetite (3%),
    tumor lysis syndrome (5%), and differentiation syndrome (8%).
    Differentiation syndrome events characterized as serious included
    pyrexia, renal failure acute, hypoxia, respiratory failure, and
    multi-organ failure

LACTATION

Many drugs are excreted in human milk and because of the potential for
adverse reactions in breastfed infants, advise women not to breastfeed
during treatment with IDHIFA and for at least 1 month after the last
dose.

Please see full Prescribing
Information
, including Boxed WARNING

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. 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.

Hyperlinks are provided as a convenience and for informational
purposes only. Celgene bears responsibility for the security or content
of external websites or websites outside of its control.

View Comments and Join the Discussion!