Total of eight approved therapies and
investigational agents being evaluated in 15 diseases
Celgene Corporation (NASDAQ:CELG) today announced more than 55
presentations reporting on investigational studies in blood and
solid tumor cancers will be presented during the 51st American
Society of Clinical Oncology meeting in Chicago, Ill. from May 30
to June 2, 2015.
Investigational data include:
- #1032 Efficacy of 12 weeks neoadjuvant
nab-paclitaxel combined with carboplatinum vs. gemcitabine in
triple-negative breast cancer: WSG-ADAPT TN randomized phase II
trial – Poster – 8 a.m., Saturday, May 30, S Hall A
- #8523 Updated analysis of
CALGB/ECOG/BMT CTN 100104: Lenalidomide (Len) vs. placebo (PBO)
maintenance therapy after single autologous stem cell transplant
(ASCT) for multiple myeloma (MM).– Poster – 8 a.m., Sunday, May 31,
S Hall A
- #8524 FIRST study: Updated overall
survival (OS) in stem cell transplant (SCT)-ineligible newly
diagnosed multiple myeloma (NDMM) patients (pts) treated with
continuous lenalidomide plus low-dose dexamethasone (Rd) vs
melphalan, prednisone, and thalidomide (MPT)– Poster- 8 a.m.,
Sunday, May 31, S Hall A
- #8525 Effect of carfilzomib,
lenalidomide, and dexamethasone (KRd) vs lenalidomide and
dexamethasone (Rd) in patients with relapsed multiple myeloma (RMM)
by line of therapy: Secondary analysis from an interim analysis of
the phase III study ASPIRE (NCT01080391) – Poster - 8 a.m., Sunday,
May 31, S Hall A
- #8030 Safety and efficacy of MPDL 3280A
(anti-PD-L1) in combination with platinum-based doublet
chemotherapy in patients with advanced non-small cell lung cancer
(NSCLC) – Poster – 8 a.m., Monday, June 1, S Hall A
- #4118 A phase 1b study of the
anti-cancer stem cell agent demcizumab (DEM) & gemcitabine
(GEM) +/- paclitaxel protein-bound particles (nab-paclitaxel) in
patients with pancreatic cancer – Poster – 8 a.m., Monday, June 1 S
Hall A
- #8504 Evaluation of complete response
rate at 30 months (CR30) as a surrogate for progression-free
survival (PFS) in first-line follicular lymphoma (FL) studies:
Results from the prospectively specified Follicular Lymphoma
Analysis of Surrogacy Hypothesis (FLASH) analysis with individual
patient data (IPD) of 3,837 patients (pts) – Oral – 10:30 a.m.,
Monday, June 1, Room E450
- #8508 ELOQUENT-2: A phase III,
randomized, open-label study of lenalidomide (Len)/dexamethasone
(dex) with/without elotuzumab (Elo) in patients (pts) with
relapsed/refractory multiple myeloma (RRMM)– Oral – 10:30 a.m.,
Tuesday, June 2, Room E345b
- #8510 Phase II MMRC trial of extended
treatment with carfilzomib (CFZ), lenalidomide (LEN), and
dexamethasone (DEX) plus autologous stem cell transplantation
(ASCT) in newly diagnosed multiple myeloma (NDMM) – Oral – 10:30
a.m., Tuesday, June 2, Room E354b
Other presentations will report on data from investigational
uses of Celgene approved therapies and pipeline candidates in solid
tumor cancers (breast, head and neck, lung, melanoma and pancreas)
and blood cancers (multiple myeloma, lymphomas, chronic lymphocytic
leukemia, acute myeloid leukemia and myelodysplastic
syndromes).
For a complete listing of abstracts, visit the ASCO Web site at
http://abstracts.asco.org/
About ABRAXANE®
ABRAXANE® 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/mm3. 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
- No toxicities occurred notably more
frequently among patients ≥65 years of age who received
ABRAXANE for MBC
- 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 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
(formerly known as the “RevAssist®” program).
Information about the REVLIMID REMS® program is
available at www.celgeneriskmanagement.com or by
calling the manufacturer’s toll-free number 1-888-423-5436.
Hematologic Toxicity (Neutropenia and
Thrombocytopenia)
REVLIMID can cause significant neutropenia and
thrombocytopenia. Eighty percent of patients with del 5q MDS had to
have a dose delay/reduction during the major study. Thirty-four
percent of patients had to have a second dose delay/reduction.
Grade 3 or 4 hematologic toxicity was seen in 80% of patients
enrolled in the study. Patients on therapy for del 5q MDS should
have their complete blood counts monitored weekly for the first 8
weeks of therapy and at least monthly thereafter. Patients may
require dose interruption and/or reduction. Patients may require
use of blood product support and/or growth factors.
Venous and Arterial
Thromboembolism
REVLIMID has demonstrated a significantly increased risk of
deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as
risk of myocardial infarction and stroke in patients with MM who
were treated with REVLIMID and dexamethasone therapy. Monitor for
and advise patients about signs and symptoms of thromboembolism.
Advise patients to seek immediate medical care if they develop
symptoms such as shortness of breath, chest pain, or arm or leg
swelling. Thromboprophylaxis is recommended and the choice of
regimen should be based on an assessment of the patient’s
underlying risks.
CONTRAINDICATIONS
Pregnancy: REVLIMID can cause fetal harm when
administered to a pregnant female and is contraindicated in females
who are pregnant. If this drug is used during pregnancy or if the
patient becomes pregnant while taking this drug, the patient should
be apprised of the potential hazard to the fetus
Allergic Reactions: REVLIMID is contraindicated in
patients who have demonstrated hypersensitivity (e.g., angioedema,
Stevens-Johnson syndrome, toxic epidermal necrolysis) to
lenalidomide
WARNINGS AND PRECAUTIONS
Embryo-Fetal Toxicity:
- REVLIMID is an analogue of thalidomide,
a known human teratogen that causes life-threatening human birth
defects or embryo-fetal death. An embryo-fetal development study in
monkeys indicates that lenalidomide produced malformations in
offspring of female monkeys who received drug during pregnancy,
similar to birth defects observed in humans following exposure to
thalidomide during pregnancy
- Females of
Reproductive Potential: Must avoid pregnancy for at least 4
weeks before beginning REVLIMID therapy, during therapy, during
dose interruptions and for at least 4 weeks after completing
therapy. Must commit either to abstain continuously from
heterosexual sexual intercourse or to use two methods of reliable
birth control beginning 4 weeks prior to initiating treatment with
REVLIMID, during therapy, during dose interruptions and continuing
for 4 weeks following discontinuation of REVLIMID. Must obtain 2
negative pregnancy tests prior to initiating therapy
- Males:
Lenalidomide is present in the semen of patients receiving the
drug. Males must always use a latex or synthetic condom during any
sexual contact with females of reproductive potential while taking
REVLIMID and for up to 28 days after discontinuing REVLIMID, even
if they have undergone a successful vasectomy. Male patients taking
REVLIMID must not donate sperm
- Blood
Donation: Patients must not donate blood during treatment
with REVLIMID and for 1 month following discontinuation of the drug
because the blood might be given to a pregnant female patient whose
fetus must not be exposed to REVLIMID
REVLIMID REMS® Program
Because of embryo-fetal risk, REVLIMID is available only through
a restricted program under a Risk Evaluation and Mitigation
Strategy (REMS) the REVLIMID REMS® program
(formerly known as the “RevAssist®” program).
Prescribers and pharmacies must be certified with the program and
patients must sign an agreement form and comply with the
requirements. Further information about the REVLIMID
REMS® program is available at
www.celgeneriskmanagement.com or by telephone at 1-888-423-5436
Hematologic Toxicity: REVLIMID can cause significant
neutropenia and thrombocytopenia. Monitor patients with neutropenia
for signs of infection. Advise patients to observe for bleeding or
bruising, especially with use of concomitant medications that may
increase risk of bleeding. MM:
Patients taking REVLIMID/dex should have their complete blood
counts (CBC) assessed every 7 days for the first 2 cycles, on days
1 and 15 of cycle 3, and every 28 days thereafter. MCL: Patients taking REVLIMID for MCL
should have their CBCs monitored weekly for the first cycle (28
days), every 2 weeks during cycles 2-4, and then monthly
thereafter. Patients may require dose interruption and/or dose
reduction. For MDS: See
Boxed WARNINGS
Venous and Arterial Thromboembolism: Venous
thromboembolic events (DVT and PE) and arterial thromboses are
increased in patients treated with REVLIMID. A significantly
increased risk of DVT (7.4%) and PE (3.7%) occurred in patients
with MM after at least one prior therapy, treated with REVLIMID/dex
compared to placebo/dex (3.1% and 0.9%) in clinical trials with
varying use of anticoagulant therapies. In NDMM study, in which
nearly all patients received antithrombotic prophylaxis, DVT (3.6%)
and PE (3.8%) were reported in the Rd continuous arm. Myocardial
infarction (MI, 1.7%) and stroke (CVA, 2.3%) are increased in
patients with MM after at least 1 prior therapy who were treated
with REVLIMID/dex therapy compared with placebo/dex (0.6%, and
0.9%) in clinical trials. In NDMM study, MI (including acute) was
reported (2.3%) in the Rd Continuous arm. Frequency of serious
adverse reactions of CVA was (0.8%) in the Rd Continuous arm.
Patients with known risk factors, including prior thrombosis, may
be at greater risk and actions should be taken to try to minimize
all modifiable factors (e.g. hyperlipidemia, hypertension,
smoking). In controlled clinical trials that did not use
concomitant thromboprophylaxis, 21.5% overall thrombotic events
occurred in patients with refractory and relapsed MM who were
treated with REVLIMID/dex compared to 8.3% thrombosis in the
placebo/dex group. Median time to first thrombosis event was 2.8
months. In NDMM study, which nearly all patients received
antithrombotic prophylaxis, overall frequency of thrombotic events
was 17.4% in combined Rd Continuous and Rd18 arms. Median time to
first thrombosis event was 4.37 months. Thromboprophylaxis is
recommended and regimen is based on patients underlying risks. ESAs
and estrogens may further increase the risk of thrombosis and their
use should be based on a benefit-risk decision. See Boxed
WARNINGS
Increased Mortality in Patients With CLL: In a clinical
trial in the first line treatment of patients with CLL, single
agent REVLIMID therapy increased the risk of death as compared to
single agent chlorambucil. In an interim analysis, there were 34
deaths among 210 patients on the REVLIMID treatment arm compared to
18 deaths among 211 patients in the chlorambucil treatment arm, and
hazard ratio for overall survival was 1.92 [95% CI: 1.08-3.41]
consistent with a 92% increase in risk of death. Serious adverse
cardiovascular reactions, including atrial fibrillation, myocardial
infarction, and cardiac failure, occurred more frequently in the
REVLIMID treatment arm. REVLIMID is not indicated and not
recommended for use in CLL outside of controlled clinical
trials
Second Primary Malignancies: In clinical trials in
patients with MM receiving REVLIMID, an increase of invasive second
primary malignancies (SPM) notably AML and MDS have been observed.
The increase of AML and MDS occurred predominantly in NDMM patients
receiving REVLIMID in combination with oral melphalan (5.3%) or
immediately following high dose intravenous melphalan and ASCT (up
to 5.2%). The frequency of AML and MDS cases in the REVLIMID/dex
arms was observed to be 0.4%. Cases of B-cell malignancies
(including Hodgkin’s Lymphomas) were observed in clinical trials
where patients received REVLIMID in the post-ASCT setting. Patients
who received REVLIMID-containing therapy until disease progression
did not show a higher incidence of invasive SPM than patients
treated in the fixed duration REVLIMID-containing arms. Monitor
patients for the development of second primary malignancies. Take
into account both the potential benefit of REVLIMID and risk of
second primary malignancies when considering treatment
Hepatotoxicity: Hepatic failure, including fatal cases,
has occurred in patients treated with REVLIMID in combination with
dex. The mechanism of drug-induced hepatotoxicity is unknown.
Pre-existing viral liver disease, elevated baseline liver enzymes,
and concomitant medications may be risk factors. Monitor liver
enzymes periodically. Stop REVLIMID upon elevation of liver
enzymes. After return to baseline values, treatment at a lower dose
may be considered
Allergic Reactions: Angioedema and serious dermatologic
reactions including Stevens-Johnson syndrome (SJS) and toxic
epidermal necrolysis (TEN) have been reported. These events can be
fatal. Patients with a prior history of Grade 4 rash associated
with thalidomide treatment should not receive REVLIMID. REVLIMID
interruption or discontinuation should be considered for Grade 2-3
skin rash. REVLIMID must be discontinued for angioedema, Grade 4
rash, exfoliative or bullous rash, or if SJS or TEN is suspected
and should not be resumed following discontinuation for these
reactions. REVLIMID capsules contain lactose. Risk-benefit of
REVLIMID treatment should be evaluated in patients with lactose
intolerance
Tumor Lysis Syndrome: Fatal instances of tumor lysis
syndrome (TLS) have been reported during treatment with
lenalidomide. The patients at risk of TLS are those with high tumor
burden prior to treatment. These patients should be monitored
closely and appropriate precautions taken
Tumor Flare Reaction: Tumor flare reaction (TFR) has
occurred during investigational use of lenalidomide for CLL and
lymphoma, and is characterized by tender lymph node swelling, low
grade fever, pain and rash
Monitoring and evaluation for TFR is recommended in patients
with MCL. Tumor flare may mimic the progression of disease (PD). In
patients with Grade 3 or 4 TFR, it is recommended to withhold
treatment with lenalidomide until TFR resolves to ≤ Grade 1. In the
MCL trial, approximately 10% of subjects experienced TFR; all
reports were Grade 1 or 2 in severity. All of the events occurred
in cycle 1 and one patient developed TFR again in cycle 11.
Lenalidomide may be continued in patients with Grade 1 and 2 TFR
without interruption or modification, at the physician’s
discretion. Patients with Grade 1 or 2 TFR may also be treated with
corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs)
and/or narcotic analgesics for management of TFR symptoms. Patients
with Grade 3 or 4 TFR may be treated for management of symptoms per
the guidance for treatment of Grade 1 and 2 TFR
Impaired Stem Cell Mobilization: A decrease in the number
of CD34+ cells collected after treatment (> 4 cycles) with
REVLIMID has been reported. In patients who are autologous stem
cell transplant (ASCT) candidates, referral to a transplant center
should occur early in treatment to optimize timing of the stem cell
collection
ADVERSE REACTIONS
Multiple Myeloma
- In newly diagnosed patients the
most frequently reported Grade 3 or 4 adverse reactions in Arm Rd
Continuous included neutropenia (27.8%), anemia (18.2%),
thrombocytopenia (8.3%), pneumonia (11.3%), asthenia (7.7.%),
fatigue (7.3%), back pain (7%), hypokalemia (6.6%), rash (7.3%),
cataract (5.8%), dyspnea (5.6%), DVT (5.6%), hyperglycemia (5.3%),
lymphopenia and leukopenia. The frequency of infections in Arm Rd
Continuous was 75%Adverse reactions reported in ≥20% of NDMM
patients in Arm Rd Continuous: diarrhea (45.5%), anemia (43.8%),
neutropenia (35%), fatigue (32.5%), back pain (32%), insomnia
(27.6%), asthenia (28.2%), rash (26.1%), decreased appetite
(23.1%), cough (22.7%), pyrexia (21.4%), muscle spasms (20.5%), and
abdominal pain (20.5%). The frequency of onset of cataracts
increased over time with 0.7% during the first 6 months and up to
9.6% by the second year of treatment with Arm Rd Continuous
- After at least one prior therapy
most adverse reactions and Grade 3 or 4 adverse reactions were more
frequent in MM patients who received the combination of
REVLIMID/dex compared to placebo/dex. Grade 3 or 4 adverse
reactions included neutropenia 33.4% vs 3.4%, febrile neutropenia
2.3% vs 0%, DVT 8.2% vs 3.4% and PE 4% vs 0.9% respectivelyAdverse
reactions reported in ≥15% of MM patients (REVLIMID/dex vs
dex/placebo): fatigue (44% vs 42%), neutropenia (42% vs 6%),
constipation (41% vs 21%), diarrhea (39% vs 27%), muscle cramp (33%
vs 21%), anemia (31% vs 24%), pyrexia (28% vs 23%), peripheral
edema (26% vs 21%), nausea (26% vs 21%), back pain (26% vs 19%),
upper respiratory tract infection (25% vs 16%), dyspnea (24% vs
17%), dizziness (23% vs 17%), thrombocytopenia (22% vs 11%), rash
(21% vs 9%), tremor (21% vs 7%), weight decreased (20% vs 15%),
nasopharyngitis (18% vs 9%), blurred vision (17% vs 11%), anorexia
(16% vs 10%), and dysgeusia (15% vs 10%)
Myelodysplastic
Syndromes
- Grade 3 and 4 adverse events reported
in ≥ 5% of patients with del 5q MDS were neutropenia (53%),
thrombocytopenia (50%), pneumonia (7%), rash (7%), anemia (6%),
leukopenia (5%), fatigue (5%), dyspnea (5%), and back pain
(5%)
- Adverse events reported in ≥15% of del
5q MDS patients (REVLIMID): thrombocytopenia (61.5%), neutropenia
(58.8%), diarrhea (49%), pruritus (42%), rash (36%), fatigue (31%),
constipation (24%), nausea (24%), nasopharyngitis (23%), arthralgia
(22%), pyrexia (21%), back pain (21%), peripheral edema (20%),
cough (20%), dizziness (20%), headache (20%), muscle cramp (18%),
dyspnea (17%), pharyngitis (16%), epistaxis (15%), asthenia (15%),
upper respiratory tract infection (15%)
Mantle Cell Lymphoma
- Grade 3 and 4 adverse events reported
in ≥5% of patients treated with REVLIMID in the MCL trial (N=134)
included neutropenia (43%), thrombocytopenia (28%), anemia (11%),
pneumonia (9%), leukopenia (7%), fatigue (7%), diarrhea (6%),
dyspnea (6%), and febrile neutropenia (6%)
- Serious adverse events reported in ≥2
patients treated with REVLIMID monotherapy for MCL included chronic
obstructive pulmonary disease, clostridium difficile colitis,
sepsis, basal cell carcinoma, and supraventricular tachycardia
- Adverse events reported in ≥15% of
patients treated with REVLIMID in the MCL trial included
neutropenia (49%), thrombocytopenia (36%), fatigue (34%), anemia
(31%), diarrhea (31%), nausea (30%), cough (28%), pyrexia (23%),
rash (22%), dyspnea (18%), pruritus (17%), peripheral edema (16%),
constipation (16%), and leukopenia (15%)
DRUG INTERACTIONS
Periodic monitoring of digoxin plasma levels, in accordance with
clinical judgment and based on standard clinical practice in
patients receiving this medication, is recommended during
administration of REVLIMID. It is not known whether there is an
interaction between dex and warfarin. Close monitoring of PT and
INR is recommended in MM patients taking concomitant warfarin.
Erythropoietic agents, or other agents, that may increase the risk
of thrombosis, such as estrogen containing therapies, should be
used with caution after making a benefit-risk assessment in
patients receiving REVLIMID
USE IN SPECIFIC POPULATIONS
Pregnancy: If pregnancy does occur during treatment,
immediately discontinue the drug. Under these conditions, refer
patient to an obstetrician/gynecologist experienced in reproductive
toxicity for further evaluation and counseling. Any suspected fetal
exposure to REVLIMID must be reported to the FDA via the MedWatch
program at 1-800-332-1088 and also to Celgene Corporation at
1-888-423-5436
Nursing Mothers: It is not known whether REVLIMID is
excreted in human milk. Because many drugs are excreted in human
milk and because of the potential for adverse reactions in nursing
infants, a decision should be made whether to discontinue nursing
or the drug, taking into account the importance of the drug to the
mother
Pediatric Use: Safety and effectiveness in patients below
the age of 18 have not been established
Renal Impairment: Since REVLIMID is primarily excreted
unchanged by the kidney, adjustments to the starting dose of
REVLIMID are recommended to provide appropriate drug exposure in
patients with moderate (CLcr 30-60 mL/min) or severe renal
impairment (CLcr < 30 mL/min) and in patients on dialysis
Please see [accompanying or enclosed, etc] full Prescribing
Information, including Boxed WARNINGS.
About Celgene
Celgene Corporation, headquartered in Summit, New Jersey, is an
integrated global pharmaceutical company engaged primarily in the
discovery, development and commercialization of innovative
therapies for the treatment of cancer and inflammatory diseases
through gene and protein regulation. For more information, please
visit www.celgene.com. Follow Celgene on Social Media:
@Celgene, Pinterest, LinkedIn and YouTube.
Forward-Looking Statements
This press release may contain 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 other reports filed with the Securities and
Exchange Commission.
Celgene:Investors:(908)
673-9628investors@celgene.comotMedia:(908)
673-2275media@celgene.com
Celgene (NASDAQ:CELG)
Historical Stock Chart
From Mar 2024 to Apr 2024
Celgene (NASDAQ:CELG)
Historical Stock Chart
From Apr 2023 to Apr 2024