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Sunday, December 6, 2015
SUMMIT, N.J.--(BUSINESS WIRE)--Celgene Corporation (NASDAQ: CELG) today announced that nearly 30
combination studies including IMiD® compounds, REVLIMID® (lenalidomide)
and POMALYST®/IMNOVID® (pomalidomide), across a range of patient
segments within multiple myeloma are being presented at the 57th
American Society of Hematology Annual Meeting (ASH).
In the U.S., REVLIMID in combination with dexamethasone is approved for
patients with multiple myeloma and POMALYST in combination with
dexamethasone is approved 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. Buy Levaquin (Levofloxacin) with no prescription These treatments are
the subject of important investigational studies in combination with
investigational and approved agents.
“At ASH this year, we are encouraged to see our IMiD® therapies forming
the backbone for combination treatments in multiple myeloma, including
new classes such as monoclonal antibodies, immunotherapy agents and
epigenetic therapies,” said Jacqualyn A. Micronase (Glyburide(Glibenclamide)) without prescription Fouse, President
Hematology/Oncology for Celgene. About Geriforte () “We have already seen recent approvals
in the treatment of relapsed multiple myeloma that are using REVLIMID
and dexamethasone as a backbone of their therapy. Buy Ipravent with no Rx These approvals and
the important research presented here at ASH have the potential to
further advance the treatment of this serious disease.”
Some of the studies presented at ASH include:
REVLIMID-based Combinations:
Bortezomib, Lenalidomide and Dexamethasone vs. About Bupron SR (Bupropion ) Lenalidomide and
Dexamethasone in Patients with Previously Untreated Multiple Myeloma
Without an Intent for Immediate Autologous Stem Cell Transplant:
Results of the Randomized Phase 3 Trial SWOG S0777
ELOQUENT-2
Update: A Phase 3, Randomized, Open-Label Study of Elotuzumab in
Combination with Lenalidomide/Dexamethasone in Patients with
Relapsed/Refractory Multiple Myeloma – 3-Year Follow-up
Efficacy
and Safety of Carfilzomib, Lenalidomide, and Dexamethasone vs. Buy Immune System online
Lenalidomide and Dexamethasone in Patients with Relapsed Multiple
Myeloma Based on Cytogenetic Risk Status: Subgroup Analysis from the
Phase 3 Study, Aspire (NCT01080391)
Ixazomib,
an Investigational Oral Proteasome Inhibitor (PI), in Combination with
Lenalidomide and Dexamethasone (IRd), Significantly Extends
Progression-Free Survival for Patients (Pts) with Relapsed and/or
Refractory Multiple Myeloma: The Phase 3 Tourmaline-MM1 Study
(NCT01564537)
Daratumumab
in Combination with Lenalidomide and Dexamethasone in Patients with
Relapsed or Relapsed and Refractory Multiple Myeloma: Updated Results
of a Phase 1/2 Study (GEN503)
A
Phase 2 Study of Modified Lenalidomide, Bortezomib, and Dexamethasone
(RVD-lite) for Transplant-Ineligible Patients with Newly Diagnosed
Multiple Myeloma
Pembrolizumab
in Combination with Lenalidomide and Low-Dose Dexamethasone for
Relapsed/Refractory Multiple Myeloma: Keynote-023
First
Interim Results of a Phase 1/2 Study of Lenalidomide in Combination
with Anti-PD-1 Monoclonal Antibody MDV9300 (CT-011) in Patients with
Relapsed/Refractory Multiple Myeloma
Phase
1/2 Trial of the Efficacy and Safety of Combination Therapy with
Lenalidomide/Bortezomib/Dexamethasone (RVD) and Panobinostat in
Transplant-Eligible Patients with Newly Diagnosed Multiple Myeloma
A
Phase 2 Study of Panobinostat with Lenalidomide and Weekly
Dexamethasone in Myeloma
Phase 1 Dose-Escalation Study of Sotatercept (ACE-011) in Combination
with Lenalidomide and Dexamethasone in Patients with Relapsed and/or
Refractory Multiple Myeloma
POMALYST-based Combinations:
A
Phase 2 Study of Anti PD-1 Antibody Pembrolizumab, Pomalidomide and
Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma
Open-Label,
Multicenter, Phase 1b Study of Daratumumab in Combination with
Pomalidomide and Dexamethasone in Patients with at Least 2 Lines of
Prior Therapy and Relapsed or Relapsed and Refractory Multiple Myeloma
Alliance
A061202. http://asthmareview.wordpress.com A Phase 1/2 Study Of Pomalidomide, Dexamethasone And Ixazomib
Versus Pomalidomide And Dexamethasone For Patients With Multiple
Myeloma Refractory To Lenalidomide And Proteasome Inhibitor Based
Therapy: Phase 1 Results
A
Phase 1, Multicenter Study of Pomalidomide, Bortezomib, and Low-Dose
Dexamethasone in Patients with Proteasome Inhibitor–Exposed and
Lenalidomide-Refractory Myeloma (trial MM-005)
ClaPd
(Clarithromycin, Pomalidomide, Dexamethasone) therapy in relapsed or
refractory multiple myeloma overcomes negative prognostic impact of
adverse cytogenetics and prior resistance to lenalidomide and
bortezomib
Oprozomib,
Pomalidomide, and Dexamethasone (OPomd) in Patients with Relapsed
and/or Refractory Multiple Myeloma: Initial Results of a Phase 1b
Study (NCT01999335)
About REVLIMID®
In the United States, REVLIMID is approved in combination with
dexamethasone for the treatment of patients with multiple myeloma.
REVLIMID is also approved in combination with dexamethasone for the
treatment of patients with multiple myeloma who have received at least
one prior therapy in nearly 70 countries, encompassing Europe, the
Americas, the Middle East and Asia, and in combination with
dexamethasone for the treatment of patients whose disease has progressed
after one therapy in Australia and New Zealand.
REVLIMID is also approved in the United States, Canada, Switzerland,
Australia, New Zealand and several Latin American countries, as well as
Malaysia and Israel, for 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 and in Europe for the treatment of patients
with transfusion-dependent anemia due to low- or intermediate-1-risk MDS
associated with an isolated deletion 5q cytogenetic abnormality when
other therapeutic options are insufficient or inadequate.
In addition, REVLIMID is approved in the United States 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.
U.S. Regulatory Information for 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 not recommended for the treatment of
patients with chronic lymphocytic leukemia (CLL) outside of controlled
clinical trials
REVLIMID® and POMALYST®/IMNOVID®
are registered trademarks of Celgene Corporation
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 .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
note 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 .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. 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 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 lenalidomide 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 and risk of second primary
malignancies when considering treatment with REVLIMID
Hepatotoxicity: Hepatic failure, including fatal cases,
has occurred in patients treated with lenalidomide 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 =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 3/4 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%
respectively
Adverse 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 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 hazard to a fetus
WARNINGS AND PRECAUTIONS
Embryo-Fetal Toxicity
Females of Reproductive Potential: Must
avoid pregnancy while taking POMALYST and for at least 4 weeks after
completing therapy. Must commit either to abstain continuously from
heterosexual sexual intercourse or to use 2 methods of reliable birth
control, beginning 4 weeks prior to initiating treatment with
POMALYST, during therapy, during dose interruptions, and continuing
for 4 weeks following discontinuation of POMALYST therapy. Must obtain
2 negative pregnancy tests prior to initiating therapy
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 28 days
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
Because of the embryo-fetal risk, POMALYST is available only
through a restricted program under a Risk Evaluation and Mitigation
Strategy (REMS) called “POMALYST REMS®.”
Prescribers and pharmacies must be certified with the program; patients
must sign an agreement form and comply with the
requirements. Further information about the POMALYST REMS®
program is available at .CelgeneRiskManagement.com
or by telephone at 1-888-423-5436.
Venous and Arterial Thromboembolism: Venous thromboembolic events
(DVT and PE) and arterial thromboembolic events (ATE) (myocardial
infarction and stroke) have been observed in patients treated with
POMALYST. In Trial 2, where anticoagulant therapies were mandated,
thromboembolic events occurred in 8.0% of patients treated with POMALYST
and low dose-dexamethasone (Low-dose Dex) vs 3.3% treated with high-dose
dexamethasone. Venous thromboembolic events (VTE) occurred in 4.7% of
patients treated with POMALYST and Low-dose Dex vs 1.3% treated with
high-dose dexamethasone. Arterial thromboembolic events include terms
for arterial thromboembolic events, ischemic cerebrovascular conditions,
and ischemic heart disease. Arterial thromboembolic events occurred in
3.0% of patients treated with POMALYST and Low-dose Dex vs 1.3% treated
with high-dose dexamethasone. 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).
Hematologic Toxicity: In trials 1 and 2 in patients who received
POMALYST + Low-dose Dex, neutropenia (46%) was the most frequently
reported Grade 3/4 adverse reaction, followed by anemia and
thrombocytopenia. Monitor patients for hematologic toxicities,
especially neutropenia. Monitor complete blood counts weekly for the
first 8 weeks and monthly therafter. 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 trials 1 and 2 in patients
who received POMALYST + Low-dose Dex, 14% experienced dizziness and 7% a
confusional state; 1% of patients experienced Grade 3 or 4 dizziness and
3% experienced a Grade 3 or 4 confusional state. 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 trials 1 and 2, patients who received POMALYST +
Low-dose Dex experienced neuropathy (18%) and peripheral neuropathy
(~12%). In trial 2, 2% of patients experienced Grade 3 neuropathy.
Risk of 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: Tumor lysis syndrome (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%). In trial 2, 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%), edema peripheral
(17.3%), peripheral neuropathy (17.3%), bone pain (18%), nausea (15%),
and muscle spasms (15.3%). Grade 3 or 4 adverse reactions included
neutropenia (48.3%), thrombocytopenia (22%), and pneumonia (15.7%).
DRUG INTERACTIONS
Pomalidomide is primarily metabolized by CYP1A2 and CYP3A. Pomalidomide
is also a substrate for P-glycoprotein (P-gp). Avoid the use of strong
CYP1A2 inhibitors. If medically necessary to co-administer strong
inhibitors of CYP1A2 in the presence of strong inhibitors of CYP3A4 and
P-gp, reduce POMALYST dose by 50%. Cigarette smoking may reduce
pomalidomide exposure due to CYP1A2 induction. Patients should be
advised that smoking may reduce the efficacy of pomalidomide.
USE IN SPECIFIC POPULATIONS
Pregnancy: 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. Report any suspected fetal exposure to POMALYST to the FDA
via the MedWatch ogram at 1-800-332-1088 and also to Celgene
Corporation at 1-888-423-5436.
Nursing Mothers: It is not known if pomalidomide is excreted in
human milk. 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 nursing infants from POMALYST, a
decision should be made whether to discontinue nursing or to discontinue
the drug, taking into account the importance of the drug to the mother.
Pediatric Use: Safety and effectiveness of POMALYST in patients
under the age of 18 have not been established.
Geriatric Use: No dosage adjustment is required for POMALYST
based on age. Patients >65 years of age were more likely than patients
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