Study Showed a Median Progression-Free Survival of 31 Months for
Patients ≤75 Years Old Receiving Lenalidomide Continuous Therapy
Compared with 12 Months for Patients not Receiving Lenalidomide
Continuous Therapy
Trend Reported for Extended Overall Survival in favor of Patients
Receiving Lenalidomide Continuous Therapy
BOUDRY, Switzerland--(BUSINESS WIRE)--Dec. 12, 2011--
Celgene International Sàrl, a subsidiary of Celgene Corporation (NASDAQ:
CELG), announced that data from the planned interim analysis of MM-015,
a phase III, randomized, double-blind study of continuous REVLIMID
(lenalidomide) therapy for the treatment of patients with newly
diagnosed multiple myeloma who were ineligible for stem cell transplant,
reported a clinically significant improvement in progression-free
survival (PFS), the primary endpoint of the study. The data, presented
at the 53rd Annual Meeting of the American Society of
Hematology, focused on a pre-specified sub-analysis of patients who were
75 years or younger.
The study of 459 patients evaluated patients receiving one of the
following treatment regimens: lenalidomide in combination with melphalan
and prednisone, followed by continuous lenalidomide alone (MPR-R)
(n=152); lenalidomide in combination with melphalan and prednisone,
followed by placebo (MPR) (n=153); and placebo, melphalan and
prednisone, followed by placebo (MP) (n=154).
In patients ≤75 years old, continuous lenalidomide therapy with MPR-R
resulted in a median PFS of 31 months, while patients in the MP arm had
a median PFS of 12 months (p<0.001). Patients in this age group treated
with MPR-R had a 70% reduction in risk of disease progression compared
with MP (HR 0.30). Additionally, a trend for extended overall survival
was observed with MPR-R compared with MP (4-year 69% vs. 58%, p=0.133).
MPR induction alone provided a significant PFS benefit of 15 months
compared with 12 months for MP (p=0.006). MPR induction also resulted in
superior response rates vs. MP (73% vs. 47%) and ≥VGPR rates of 35% vs.
11%, respectively. Median time to response was 2 months for MPR vs. 3
months for MP.
The preplanned landmark analysis calculated PFS from maintenance entry
for MPR-R and MPR and demonstrated that lenalidomide maintenance reduced
the risk of progression by 65% for all patients irrespective of age (HR
0.34).
Induction with MPR in patients ≤75 years old had an acceptable safety
profile, allowing the majority of patients to reach maintenance therapy
with lenalidomide. During the induction phase, discontinuation resulted
due to adverse events in 12% of MPR and 4% of MP patients. The most
common grade 4 hematological adverse events during induction for MPR and
MP included neutropenia (31% and 7%), thrombocytopenia (7% and 4%), and
anemia (2% and 2%). The most frequent grade 3 or 4 non-hematological
adverse events were infections (8% and 6%) and bone pain (3% and 4%).
Maintenance therapy with lenalidomide was well tolerated, with no
evidence of cumulative toxicities. The most frequent grade 4
hematological adverse events during maintenance for MPR-R and MPR were
thrombocytopenia (4% and 3%), anemia (3% and 1%), and neutropenia (1%
and 0%). The most frequent grade 3 or 4 non-hematological adverse events
included infections (5% and 3%), bone pain (5% and 1%) and fatigue (3%
and 1%).
The study reported hematological and solid tumor second primary
malignancies (SPMs) during induction and maintenance that were below the
expected corresponding incidence rates in this disease setting including
12/150 in the MPR-R arm (3%), 10/152 in the MPR arm (2.6%) and 4/153 in
the MP arm (1%).
These data are from an investigational study. REVLIMID is not approved
as an initial treatment for patients with multiple myeloma.
About REVLIMID®
REVLIMID is 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 anaemia due to low- or
intermediate-1-risk MDS associated with a deletion 5q cytogenetic
abnormality with or without additional cytogenetic abnormalities.
Marketing Authorization Applications are currently being evaluated in a
number of other countries.
Since 1998, Celgene continues to be a pioneer in creating environments
in which patients can benefit from our disease-altering therapies
safely. As a result, hundreds of thousands of patients worldwide have
accessed the clinical benefits of our therapies through our
performance-based risk management programs including, S.T.E.P.S.®,
RevAssist® and RevMate®, which form the foundation
of our commitment to patient safety.
REVLIMID® (lenalidomide) in combination with
dexamethasone is indicated for the treatment of multiple myeloma (MM)
patients who have received at least one prior therapy.
REVLIMID is indicated for patients with transfusion-dependent anaemia
due to Low- or Intermediate-1–risk myelodysplastic syndromes (MDS)
associated with a deletion 5q cytogenetic abnormality with or without
additional cytogenetic abnormalities.
Important Safety Information
WARNING: FETAL RISK, HEMATOLOGIC TOXICITY, and
DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM
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 death to a developing baby. In
women of childbearing potential, obtain 2 negative pregnancy tests
before starting REVLIMID treatment. Women of childbearing potential must
use 2 forms of contraception or continuously abstain from heterosexual
sex during and for 4 weeks after REVLIMID treatment. To avoid fetal
exposure to lenalidomide, REVLIMID is only available in the United
States under a restricted distribution program called “RevAssist®.”
Information about the RevAssist program is available at www.REVLIMID.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. (see DOSAGE
and ADMINISTRATION)
DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM
REVLIMID has demonstrated a significantly increased risk of deep vein
thrombosis (DVT) and pulmonary embolism (PE) in patients with MM who
were treated with REVLIMID and dexamethasone therapy. Patients and
physicians are advised to be observant for the signs and symptoms of
thromboembolism. Patients should be instructed to seek medical care if
they develop symptoms such as shortness of breath, chest pain, or arm or
leg swelling. It is not known whether prophylactic anticoagulation or
antiplatelet therapy prescribed in conjunction with REVLIMID may lessen
the potential for venous thromboembolic events. The decision to take
prophylactic measures should be done carefully after an assessment of an
individual patient’s underlying risk factors.
CONTRAINDICATIONS:
Pregnancy Category X:
-
Lenalidomide is contraindicated in pregnant women and women capable of
becoming pregnant. Females of childbearing potential may be treated
with lenalidomide provided adequate precautions are taken to avoid
pregnancy
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:
Fetal Risk:
-
REVLIMID is an analogue of thalidomide, a known human teratogen that
causes life-threatening human birth defects. An embryofetal
development study in non-human primates indicates that lenalidomide
produced malformations in the offspring of female monkeys who received
the drug during pregnancy, similar to birth defects observed in humans
following exposure to thalidomide during pregnancy. If REVLIMID is
used during pregnancy, it may cause birth defects or death to a
developing baby
-
Females of childbearing potential must be advised to avoid pregnancy
while on REVLIMID. Two effective contraceptive methods should be used
during therapy, during therapy interruptions, and for at least 4 weeks
after completing therapy
-
Male Patients: It is not known whether lenalidomide is present in the
semen of patients receiving the drug. Therefore, males receiving
REVLIMID must always use a latex condom during any sexual contact with
females of childbearing potential, even if they have undergone a
successful vasectomy
Reproductive Risk and Special Prescribing Requirements (RevAssist
Program):
-
Because of this potential toxicity and to avoid fetal exposure,
REVLIMID is only available under a special restricted distribution
program called “RevAssist.” Prescribers and pharmacists registered
with the program can prescribe and dispense the product to patients
who are registered and meet all the conditions of the RevAssist program
Hematologic Toxicity—Multiple Myeloma:
-
REVLIMID can cause significant neutropenia and thrombocytopenia
-
Patients taking REVLIMID for MM should have their complete blood
counts monitored every 2 weeks for the first 12 weeks and then monthly
thereafter
-
In the pooled MM studies Grade 3 and 4 hematologic toxicities were
more frequent in patients treated with the combination of REVLIMID and
dexamethasone than in patients treated with dexamethasone alone
-
Patients may require dose interruption and/or dose reduction
Deep Vein Thrombosis:
-
Venous thromboembolic events (predominantly deep venous thrombosis and
pulmonary embolism) have occurred in patients with MM treated with
lenalidomide combination therapy and patients with MDS treated with
lenalidomide monotherapy
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
Tumour Lysis Syndrome:
-
Fatal instances of tumour lysis syndrome have been reported during
treatment with lenalidomide. The patients at risk of tumour lysis
syndrome are those with high tumour burden prior to treatment. These
patients should be monitored closely and appropriate precautions taken
Tumour Flare Reaction:
-
Tumour flare reaction has occurred during investigational use of
lenalidomide for chronic lymphocytic leukaemia (CLL) and lymphoma, and
is characterized by tender lymph node swelling, low grade fever, pain
and rash. Treatment of CLL or lymphoma with lenalidomide outside of a
well-monitored clinical trial is discouraged
DRUG INTERACTIONS:
-
Erythropoietic agents, or other agents, that may increase the risk of
thrombosis, such as oestrogen containing therapies, should be used
with caution in MM patients receiving lenalidomide with dexamethasone
USE IN SPECIAL POPULATIONS:
Nursing Mothers:
-
It is not known whether REVLIMID is excreted in human milk
-
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
Geriatric Use:
-
Since elderly patients are more likely to have decreased renal
function, care should be taken in dose selection. Monitor renal
function
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 or severe
renal impairment (CLcr < 60 mL/min) and in patients on dialysis
ADVERSE REACTIONS:
Multiple Myeloma
-
In the REVLIMID/dexamethasone treatment group, 269 patients (76%)
underwent at least one dose interruption with or without a dose
reduction of REVLIMID compared with 199 patients (57%) in the
placebo/dexamethasone treatment group
-
Of these patients who had one dose interruption with or without a dose
reduction, 50% in the REVLIMID/dexamethasone treatment group underwent
at least one additional dose interruption with or without a dose
reduction compared with 21% in the placebo/dexamethasone treatment
group
-
Most adverse events and Grade 3/4 adverse events were more frequent in
MM patients who received the combination of REVLIMID/dexamethasone
compared with placebo/dexamethasone
-
Adverse reactions reported in ≥15% of MM patients
(REVLIMID/dexamethasone vs. dexamethasone/placebo): fatigue (44% vs.
42%), neutropenia (42% vs. 6%), constipation (41% vs. 21%), diarrhoea
(39% vs. 27%), muscle cramp (33% vs. 21%), anaemia (31% vs. 24%),
pyrexia (28% vs. 23%), peripheral oedema (26% vs. 21%), nausea (26%
vs. 21%), back pain (26% vs. 19%), upper respiratory tract infection
(25% vs. 16%), dyspnoea (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
-
Thrombocytopenia (61.5%; 91/148) and neutropenia (58.8%; 87/148) were
the most frequently reported adverse events observed in the del 5q MDS
population
-
Other adverse events reported in ≥15% of del 5q MDS patients
(REVLIMID): diarrhoea (49%), pruritus (42%), rash (36%), fatigue
(31%), constipation (24%), nausea (24%), nasopharyngitis (23%),
arthralgia (22%), pyrexia (21%), back pain (21%), peripheral oedema
(20%), cough (20%), dizziness (20%), headache (20%), muscle cramp
(18%), dyspnoea (17%), pharyngitis (16%), epistaxis (15%), asthenia
(15%), upper respiratory tract infection (15%)
DOSAGE AND ADMINISTRATION:
-
Treatment is continued or modified based upon clinical and laboratory
findings. Dosing modifications are recommended to manage Grade 3 or 4
neutropenia or thrombocytopenia or other Grade 3 or 4 toxicity judged
to be related to REVLIMID
-
For other Grade 3 or 4 toxicities judged to be related to REVLIMID,
hold treatment and restart at next lower dose level when toxicity has
resolved to ≤Grade 2
Please see full Prescribing Information, including Boxed WARNINGS,
CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS.
About Celgene International Sàrl
Celgene International Sàrl, located in Boudry, in the Canton of
Neuchâtel, 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 the Company's website at www.celgene.com.
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.
Source: Celgene International Sàrl
Investors:
+41 32 729 8303
ir@celgene.com
Media:
+41
32 729 8304
media@celgene.com
