Results from Phase III Study (MM-003) of Pomalidomide Plus Low-Dose
Dexamethasone versus High-Dose Dexamethasone in Relapsed and Refractory
Multiple Myeloma Patients Published in The Lancet Oncology
Pomalidomide plus low-dose dexamethasone demonstrated significantly longer
median progression-free survival and overall survival at a median follow-up of
BOUDRY, Switzerland -- September 5, 2013
Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation
(NASDAQ:CELG), today announced that updated results from MM-003, a phase III
multi-center, randomized open-label study (n=455) of pomalidomide (marketed as
POMALYST^® in the U.S. and IMNOVID^® in the E.U.) plus low-dose dexamethasone,
were published online ahead of print in The Lancet Oncology.
The study compared oral pomalidomide plus low-dose dexamethasone with
high-dose dexamethasone in patients with refractory or relapsed and refractory
multiple myeloma who have failed at least two prior therapies with both
bortezomib and lenalidomide, administered alone or in combination.
At the interim analysis (ASH 2012, median follow-up 4.2 months), the study met
its primary endpoint as pomalidomide plus low-dose dexamethasone demonstrated
a significant improvement in progression-free survival (PFS) (3.8 months vs
1.9 months HR 0.41 p<0.0001) compared with high-dose dexamethasone. There was
also a significant improvement in the key secondary endpoint of overall
survival (OS) (11.9 months vs 7.8 months HR 0.53 p<0.0002) compared with
high-dose dexamethasone even though 45 patients in the high-dose dexamethasone
arm crossed over and received pomalidomide.
Additionally, the Data Monitoring Committee recommended that patients who had
not yet progressed in the high-dose dexamethasone arm should have access to
pomalidomide with or without low-dose dexamethasone.
At a median follow-up of 10.0 months, an updated PFS analysis and final OS
analysis were conducted. Pomalidomide plus low-dose dexamethasone continued to
demonstrate significantly longer PFS, the primary endpoint, compared with
high-dose dexamethasone (4.0 months vs. 1.9 months, HR=0.48, p<0.0001).
Additionally, pomalidomide plus low-dose dexamethasone demonstrated a
significant improvement in OS compared with high-dose dexamethasone (12.7
months vs. 8.1 months, HR=0.74, p=0.0285). Overall response rate for patients
receiving pomalidomide plus low-dose dexamethasone was 31% compared with 10%
for patients receiving high-dose dexamethasone (p<0.0001).
The most common grade 3-4 hematological adverse events in the pomalidomide
plus low-dose dexamethasone and high-dose dexamethasone arms, respectively,
were: neutropenia (48% 143/300 vs. 16% 24/150), anemia (33% 99/300 vs. 37%
55/150) and thrombocytopenia (22% 67/300 vs. 26% 39/150). Grade 3-4
non-hematological adverse events in the pomalidomide plus low-dose
dexamethasone and high-dose dexamethasone arms, respectively, included:
pneumonia (13% 38/300 vs. 8% 12/150), bone pain (7% 21/300 vs. 5% 7/150) and
fatigue (5% 16/300 vs. 6% 9/150). Four patients in the pomalidomide plus
low-dose dexamethasone arm and one patient in the high-dose dexamethasone arm
developed second primary malignancies. Of these, two patients in the
pomalidomide plus low-dose dexamethasone arm had invasive solid tumor cancers
and two patients in this group and the one in the high-dose dexamethasone
group had non-invasive cancers (basal-cell skin cancers). Treatment-related
adverse events led to treatment discontinuation in 4% of patients in the
pomalidomide plus low-dose dexamethasone arm and 6% of patients in the
high-dose dexamethasone arm.
Patients in the pomalidomide plus low-dose dexamethasone arm received 4 mg of
oral pomalidomide on days 1-21 of each 28-day cycle. Oral dexamethasone was
given at 40 mg on days 1, 8, 15, and 22); for patients older than 75 years,
dexamethasone was administered at 20 mg weekly.
Patients in the comparator arm were treated with 40 mg oral high-dose
dexamethasone on days 1-4, 9-12 and 17-20 of each 28-day cycle, until disease
progression; patients older than 75 years received 20 mg oral dexamethasone on
the same schedule.
Results of the MM-003 trial formed the basis of an August 2013 approval by the
European Medicines Agency in patients with relapsed and refractory multiple
myeloma who have received at least two prior therapies including both
lenalidomide and bortezomib and have demonstrated disease progression on the
For more information, visit
Important Safety Information based on approved U.S. Label for Pomalyst (Trade
name for Pomalidomide Celgene in the U.S.)
WARNING: EMBRYO-FETAL TOXICITY and VENOUS THROMBOEMBOLISM
*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
*Deep Venous Thrombosis (DVT) and Pulmonary Embolism (PE) occur in patients
with multiple myeloma treated with POMALYST. Prophylactic anti-thrombotic
measures were employed in the clinical trial. Consider prophylactic
measures after assessing an individual patient’s underlying risk factors
*POMALYST can cause fetal harm 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 a fetus
*Pomalidomide is a thalidomide analogue and is teratogenic in both rats and
rabbits when administered during the period of organogenesis.
WARNINGS AND PRECAUTIONS
*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
*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 the drug 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 distribution program under a Risk Evaluation and Mitigation
Strategy (REMS) called “POMALYST REMS.” Prescribers and pharmacists 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 Thromboembolism: Patients receiving POMALYST have developed venous
thromboembolic events reported as serious adverse reactions. In the trial, all
patients were required to receive prophylaxis or antithrombotic treatment. The
rate of DVT or PE was 3%. Consider anticoagulation prophylaxis after an
assessment of each patient’s underlying risk factors.
Hematologic Toxicity: Neutropenia of any grade was reported in 50% of patients
and was the most frequently reported Grade 3/4 adverse event, followed by
anemia and thrombocytopenia. Monitor patients for hematologic toxicities,
especially neutropenia, with complete blood counts weekly for the first 8
weeks and monthly thereafter. Treatment is continued or modified for Grade 3
or 4 hematologic toxicities based upon clinical and laboratory findings.
Dosing interruptions and/or modifications are recommended to manage
neutropenia and thrombocytopenia.
Hypersensitivity Reactions: Patients with a prior history of serious
hypersensitivity associated with thalidomide or lenalidomide were excluded
from studies and may be at higher risk of hypersensitivity.
Dizziness and Confusional State: 18% of patients experienced dizziness and 12%
of patients experienced a confusional state; 1% of patients experienced grade
3/4 dizziness, and 3% of patients experienced grade 3/4 confusional state.
Instruct patients to avoid situations where dizziness or confusion may be a
problem and not to take other medications that may cause dizziness or
confusion without adequate medical advice.
Neuropathy: 18% of patients experienced neuropathy (approximately 9%
peripheral neuropathy). There were no cases of grade 3 or higher neuropathy
adverse reactions reported.
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.
In the clinical trial MM-002 of 219 patients who received POMALYST alone
(n=107) or POMALYST + low-dose dexamethasone (low-dose dex) (n=112), all
patients had at least one treatment-emergent adverse reaction.
*In the POMALYST alone versus POMALYST + low dose dexamethasone arms,
respectively, most common adverse reactions (≥30%) included fatigue and
asthenia (55%, 63%), neutropenia (52%, 47%), anemia (38%, 39%),
constipation (36%, 35%), nausea (36%,22%), diarrhea (34%, 33%), dyspnea
(34%, 45%), upper respiratory tract infection (32%, 25%), back pain (32%,
30%), and pyrexia (19%, 30%)
*90% of patients treated with POMALYST alone and 88% of patients treated
with POMALYST + low-dose dex had at least one treatment-emergent NCI CTC
Grade 3 or 4 adverse reaction
*In the POMALYST alone versus POMALYST + low dose dexamethasone arms,
respectively, most common Grade 3/4 adverse reactions (≥15%) included
neutropenia (47%, 38%), anemia (22%, 21%), thrombocytopenia (22%, 19%),
and pneumonia (16%, 23%). For other Grade 3 or 4 toxicities besides
neutropenia and thrombocytopenia, hold treatment and restart treatment at
1 mg less than the previous dose when toxicity has resolved to less than
or equal to Grade 2 at the physician’s discretion
*67% of patients treated with POMALYST and 62% of patients treated with
POMALYST + low-dose dex had at least one treatment-emergent serious
*In the POMALYST alone versus POMALYST + low dose dexamethasone arms,
respectively, most common serious adverse reactions (≥5%) were pneumonia
(14%, 19%), renal failure (8%, 6%), dyspnea (5%, 6%), sepsis (6%, 3%),
pyrexia (3%, 5%) dehydration (5%, 3%), hypercalcemia (5%, 2%),urinary
tract infection (0%, 5%), and febrile neutropenia (5%, 1%)
No formal drug interaction studies have been conducted with POMALYST.
Pomalidomide is primarily metabolized by CYP1A2 and CYP3A. Pomalidomide is
also a substrate for P-glycoprotein (P-gp). Coadministration of POMALYST with
drugs that are strong inhibitors or inducers of CYP1A2, CYP3A, or P-gp should
be avoided. Cigarette smoking may reduce pomalidomide exposure due to CYP1A2
induction. Patients should be advised that smoking may reduce the efficacy of
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 program 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 greater than or equal to 65 years of age were more likely than
patients less than or equal to 65 years of age to experience pneumonia.
Renal and Hepatic Impairment: Pomalidomide is metabolized in the liver.
Pomalidomide and its metabolites are primarily excreted by the kidneys. The
influence of renal and hepatic impairment on the safety, efficacy, and
pharmacokinetics of pomalidomide has not been evaluated. Avoid POMALYST in
patients with a serum creatinine >3.0 mg/dL. Avoid POMALYST in patients with
serum bilirubin >2.0 mg/dL and AST/ALT >3.0 x ULN.
Please see full U.S. Prescribing Information, including Boxed WARNINGS,
CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS.
Pomalidomide is an oral immunomodulatory drug (IMiD^®) with a multimodal
mechanism of action consisting of three main effects demonstrated in vitro:
direct antimyeloma, stromal inhibitory effects and immunomodulatory effects.
Pomalidomide in combination with dexamethasone has been approved in the EU for
the treatment of adult patients with relapsed and refractory multiple myeloma
who have received at least two prior therapies including lenalidomide and
bortezomib and have demonstrated disease progression on the last therapy.
In addition to the EC decision for the EU, pomalidomide is approved in the
United States under the brand name POMALYST^® and is under review in other
In the United States, Pomalyst is approved for use in patients with multiple
myeloma who have received at least two prior therapies including lenalidomide
and bortezomib and have demonstrated disease progression on or within 60 days
of completion on the last therapy. Approval is based on response rate.
Clinical benefit, such as improvement in survival or symptoms, has not been
Celgene International Sàrl, located in Boudry, Switzerland, is a wholly-owned
subsidiary and international headquarters of Celgene Corporation. 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.
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"estimates," "plans," "will," “outlook” and similar expressions.
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results or outcomes may differ materially from those implied by the
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Celgene International Sàrl
+41 32 729 8303
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