Revlimid plus rituximab is the first
chemotherapy-free combination regimen approved in Europe for
patients with follicular lymphoma who have relapsed or did not
respond to previous treatment
Approval was based on data from the phase 3
AUGMENT study, which showed statistically significant improvements
in median progression-free survival in patients treated with the
combination over rituximab-placebo monotherapy
Bristol-Myers Squibb Company (NYSE: BMY) today announced that
the European Commission (EC) has approved a new indication for
Revlimid (lenalidomide), in combination with rituximab (anti-CD20
antibody), for the treatment of adult patients with previously
treated follicular lymphoma (FL) (Grade 1-3a). This combination of
Revlimid and rituximab (R2) is the first chemotherapy-free
combination regimen approved for patients with FL by the EC.
“This approval is a significant milestone for patients with
follicular lymphoma whose disease is not responding to current
therapy or has returned following prior treatment. In the phase 3
AUGMENT sudy, patients receiving R2 experienced extended periods of
disease remission versus patients receiving rituximab plus
placebo,” said Nadim Ahmed, President of Hematology at
Bristol-Myers Squibb.
FL is a subtype of indolent, but incurable, non-Hodgkin lymphoma
(NHL) which is associated with immune system dysfunction.1,2 There
remains an unmet medical need for novel treatments for patients who
have relapsed or become refractory to their previous treatment. It
has been hypothesized that the combination therapy, R2, works with
the patient’s immune system using the immunomodulatory properties
of Revlimid along with the CD20 antibody-targeted mechanism of
action of rituximab in order to help the patient’s own immune
system fight the cancer.3
“Immune dysfunction is a defining aspect of indolent NHL,
including follicular lymphoma,” said Prof. John Gribben, President
of the European Hematology Association and Centre for
Haemato-Oncology, Barts Cancer Institute, in England. “By utilizing
the patient’s own immune system, R2 represents a new approach to
treatment in follicular lymphoma, giving patients a
chemotherapy-free option with demonstrated efficacy.”
The approval of R2 is based primarily on results from the
randomized, multi-center, double-blind, phase 3 AUGMENT study,
which evaluated the efficacy and safety of the R² combination
versus rituximab plus placebo in patients with previously treated
FL (n=295) or marginal zone lymphoma (MZL) (n=63).4
In AUGMENT, treatment with R2 demonstrated a statistically
significant improvement in the primary endpoint of median
progression-free survival (PFS) (EMA Censoring Rules), evaluated by
an independent review committee, versus rituximab plus placebo. The
median PFS was 39.4 months for FL patients treated with R2 and 13.8
months for those treated with rituximab-placebo (HR: 0.40; 95% CI,
0.29-0.55; P<0.0001). Median follow-up time was 29.2 months
(range, 0.5-50.9) in the intent to treat population (n=295).4
In AUGMENT the adverse reactions of any grade observed more
frequently in the FL R2 arm compared with the placebo/rituximab arm
(with at least 2% higher frequency between arms) were neutropenia
(58.2%), diarrhea (30.8%), leukopenia (28.8%), constipation
(21.9%), cough (21.9%) and fatigue (21.9%).4
In addition to AUGMENT, findings from the MAGNIFY study were
included as support for the safety and the efficacy of Revlimid
plus rituximab in patients with relapsed or refractory FL,
including rituximab refractory FL patients.5
About Follicular
Lymphoma
Lymphoma is a blood cancer that develops in lymphocytes, a type
of white blood cell in the immune system that helps protect the
body from infection.6 There are two classes of lymphoma – Hodgkin
lymphoma and non-Hodgkin lymphoma (NHL) – each with specific
subtypes that determine how the cancer behaves, spreads and should
be treated.3,7,8 Other differentiating factors of lymphomas are
what type of lymphocyte is affected (T cell or B cell) and how
mature the cells are when they become cancerous.8
FL is the most common indolent (slow-growing) form of NHL,
accounting for approximately 25% of all NHL patients.9,10 Most
patients present with advanced disease when lymphoma-related
symptoms appear (e.g., nodal disease, B symptoms, cytopenia) and
receive systemic chemoimmunotherapy.9 While FL patients are
generally responsive to initial treatment, the disease course is
characterized by recurrent relapses over time with shorter
remission periods.11
About AUGMENT
AUGMENT is a phase 3, randomized, double-blind clinical trial
evaluating the efficacy and safety of Revlimid (lenalidomide) in
combination with rituximab (R²) versus rituximab plus placebo in
patients with previously treated follicular lymphoma (FL) or
marginal zone lymphoma (MZL). AUGMENT included patients diagnosed
with MZL or Grade 1, 2 or 3a FL, who were previously treated with
at least 1 prior systemic therapy and two previous doses of
rituximab.4 Patients were documented relapsed, refractory or
progressive disease following systemic therapy, but were not
rituximab-refractory.12
The primary endpoint was progression-free survival, defined as
the time from date of randomization to the first observation of
disease progression or death due to any cause.12 Secondary and
exploratory endpoints included overall response rate, durable
complete response rate, complete response rate, duration of
response, duration of complete response, overall survival,
event-free survival and time to next anti-lymphoma therapy.4,12
Bristol-Myers Squibb: Advancing Cancer
Research
At Bristol-Myers Squibb, patients are at the center of
everything we do. The goal of our cancer research is to increase
quality, long-term survival and make cure a possibility. We harness
our deep scientific experience, cutting-edge technologies and
discovery platforms to discover, develop and deliver novel
treatments for patients.
Building upon our transformative work and legacy in hematology
and Immuno-Oncology that has changed survival expectations for many
cancers, our researchers are advancing a deep and diverse pipeline
across multiple modalities. In the field of immune cell therapy,
this includes registrational chimeric antigen receptor (CAR) T-cell
agents for numerous diseases, and a growing early-stage pipeline
that expands cell and gene therapy targets, and technologies. We
are developing cancer treatments directed at key biological
pathways using our protein homeostasis platform, a research
capability that has been the basis of our approved therapies for
multiple myeloma and several promising compounds in early to
mid-stage development. Our scientists are targeting different
immune system pathways to address interactions between tumors, the
microenvironment and the immune system to further expand upon the
progress we have made and help more patients respond to treatment.
Combining these approaches is key to delivering new options for the
treatment of cancer and addressing the growing issue of resistance
to immunotherapy. We source innovation internally, and in
collaboration with academia, government, advocacy groups and
biotechnology companies, to help make the promise of
transformational medicines a reality for patients.
About Revlimid
Revlimid is approved in Europe and the United States as
monotherapy, indicated for the maintenance treatment of adult
patients with newly diagnosed multiple myeloma (MM) who have
undergone autologous stem cell transplantation. Revlimid as
combination therapy is approved in Europe, in the United States, in
Japan and in around 25 other countries for the treatment of adult
patients with previously untreated MM who are not eligible for
transplant. Revlimid is also approved in combination with
dexamethasone for the treatment of patients with MM 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 Europe for the treatment of
patients with mantle cell lymphoma (MCL) and in the United States
for the treatment of patients with MCL whose disease has relapsed
or progressed after two prior therapies, one of which included
bortezomib. In Switzerland, Revlimid is indicated for the treatment
of patients with relapsed or refractory MCL after prior therapy
that included bortezomib and chemotherapy/rituximab.
Revlimid is also approved in the United States in combination
with a rituximab product. It is indicated for the treatment of
adult patients with previously treated FL and adult patients with
previously treated marginal zone lymphoma.
Revlimid is not indicated and is not recommended for the
treatment of patients with chronic lymphocytic leukemia (CLL)
outside of controlled clinical trials.
U.S. FDA-APPROVED INDICATIONS FOR
REVLIMID®
REVLIMID® (lenalidomide) in combination with dexamethasone
(dex) is indicated for the treatment of adult patients with
multiple myeloma (MM).
REVLIMID is indicated as maintenance therapy in adult
patients with MM following autologous hematopoietic stem cell
transplantation (auto-HSCT).
REVLIMID is indicated for the treatment of adult 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 adult patients
with mantle cell lymphoma (MCL) whose disease has relapsed or
progressed after two prior therapies, one of which included
bortezomib.
REVLIMID in combination with a rituximab product is indicated
for the treatment of adult patients with previously treated
follicular lymphoma (FL).
REVLIMID in combination with a rituximab product is indicated
for the treatment of adult patients with previously treated
marginal zone lymphoma (MZL).
REVLIMID is not indicated and is not recommended for the
treatment of patients with chronic lymphocytic leukemia (CLL)
outside of controlled clinical trials.
REVLIMID is only available through a restricted distribution
program, REVLIMID REMS®.
Important Safety Information
WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and
VENOUS and ARTERIAL THROMBOEMBOLISM
Embryo-Fetal Toxicity
Do not use REVLIMID during pregnancy. Lenalidomide, a
thalidomide analogue, caused limb abnormalities in a developmental
monkey study. Thalidomide is a known human teratogen that causes
severe life-threatening human birth defects. If lenalidomide is
used during pregnancy, it may cause birth defects or embryo-fetal
death. In females of reproductive potential, obtain 2 negative
pregnancy tests before starting REVLIMID treatment. Females of
reproductive potential must use 2 forms of contraception or
continuously abstain from heterosexual sex during and for 4 weeks
after REVLIMID treatment. To avoid embryo-fetal exposure to
lenalidomide, REVLIMID is only available through a restricted
distribution program, the REVLIMID REMS® program.
Information about the REVLIMID REMS program is available at
www.celgeneriskmanagement.com or by calling the manufacturer’s
toll-free number 1-888-423-5436.
Hematologic Toxicity (Neutropenia and
Thrombocytopenia)
REVLIMID can cause significant neutropenia and
thrombocytopenia. Eighty percent of patients with del 5q MDS had to
have a dose delay/reduction during the major study. Thirty-four
percent of patients had to have a second dose delay/reduction.
Grade 3 or 4 hematologic toxicity was seen in 80% of patients
enrolled in the study. Patients on therapy for del 5q MDS should
have their complete blood counts monitored weekly for the first 8
weeks of therapy and at least monthly thereafter. Patients may
require dose interruption and/or reduction. Patients may require
use of blood product support and/or growth factors.
Venous and Arterial
Thromboembolism
REVLIMID has demonstrated a significantly increased risk of
deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as
risk of myocardial infarction and stroke in patients with MM who
were treated with REVLIMID and dexamethasone therapy. Monitor for
and advise patients about signs and symptoms of thromboembolism.
Advise patients to seek immediate medical care if they develop
symptoms such as shortness of breath, chest pain, or arm or leg
swelling. Thromboprophylaxis is recommended and the choice of
regimen should be based on an assessment of the patient’s
underlying risks.
CONTRAINDICATIONS
Pregnancy: REVLIMID can cause fetal harm when
administered to a pregnant female and is contraindicated in females
who are pregnant. If this drug is used during pregnancy or if the
patient becomes pregnant while taking this drug, the patient should
be apprised of the potential risk to the fetus.
Severe Hypersensitivity Reactions: REVLIMID is
contraindicated in patients who have demonstrated severe
hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic
epidermal necrolysis) to lenalidomide.
WARNINGS AND PRECAUTIONS
Embryo-Fetal Toxicity: See Boxed WARNINGS.
- Females of Reproductive Potential:
See Boxed WARNINGS.
- Males: Lenalidomide is present in
the semen of patients receiving the drug. Males must always use a
latex or synthetic condom during any sexual contact with females of
reproductive potential while taking REVLIMID and for up to 4 weeks
after discontinuing REVLIMID, even if they have undergone a
successful vasectomy. Male patients taking REVLIMID must not donate
sperm.
- Blood Donation: Patients must not
donate blood during treatment with REVLIMID and for 4 weeks
following discontinuation of the drug because the blood might be
given to a pregnant female patient whose fetus must not be exposed
to REVLIMID.
REVLIMID REMS® Program: See Boxed WARNINGS. Prescribers
and pharmacies must be certified with the REVLIMID REMS program by
enrolling and complying with the REMS requirements; pharmacies must
only dispense to patients who are authorized to receive REVLIMID.
Patients must sign a Patient-Physician Agreement Form and comply
with REMS requirements; female patients of reproductive potential
who are not pregnant must comply with the pregnancy testing and
contraception requirements and males must comply with contraception
requirements.
Hematologic Toxicity: REVLIMID can cause significant
neutropenia and thrombocytopenia. Monitor patients with neutropenia
for signs of infection. Advise patients to observe for bleeding or
bruising, especially with use of concomitant medications that may
increase risk of bleeding. Patients may require a dose interruption
and/or dose reduction. MM:
Monitor complete blood counts (CBC) in patients taking REVLIMID +
dexamethasone or REVLIMID as maintenance therapy, every 7 days for
the first 2 cycles, on days 1 and 15 of cycle 3, and every 28 days
thereafter. MDS: Monitor CBC in
patients on therapy for del 5q MDS, weekly for the first 8 weeks of
therapy and at least monthly thereafter. See Boxed WARNINGS
for further information. MCL:
Monitor CBC in patients taking REVLIMID for MCL weekly for the
first cycle (28 days), every 2 weeks during cycles 2-4, and then
monthly thereafter. FL/MZL:
Monitor CBC in patients taking REVLIMID for FL or MZL weekly for
the first 3 weeks of Cycle 1 (28 days), every 2 weeks during Cycles
2-4, and then monthly thereafter.
Venous and Arterial Thromboembolism: See Boxed WARNINGS.
Venous thromboembolic events (DVT and PE) and arterial thromboses
(MI and CVA) are increased in patients treated with REVLIMID.
Patients with known risk factors, including prior thrombosis, may
be at greater risk and actions should be taken to try to minimize
all modifiable factors (e.g., hyperlipidemia, hypertension,
smoking). Thromboprophylaxis is recommended and the regimen should
be based on the patient’s underlying risks. ESAs and estrogens may
further increase the risk of thrombosis and their use should be
based on a benefit-risk decision.
Increased Mortality in Patients With CLL: In a clinical
trial in the first-line treatment of patients with CLL,
single-agent REVLIMID therapy increased the risk of death as
compared to single-agent chlorambucil. Serious adverse
cardiovascular reactions, including atrial fibrillation, myocardial
infarction, and cardiac failure, occurred more frequently in the
REVLIMID arm. REVLIMID is not indicated and not recommended for use
in CLL outside of controlled clinical trials.
Second Primary Malignancies (SPM): In clinical trials in
patients with MM receiving REVLIMID and in patients with FL or MZL
receiving REVLIMID + rituximab therapy, an increase of hematologic
plus solid tumor SPM, notably AML, have been observed. In patients
with MM, MDS was also observed. Monitor patients for the
development of SPM. Take into account both the potential benefit of
REVLIMID and risk of SPM when considering treatment.
Increased Mortality With Pembrolizumab: In clinical
trials in patients with MM, the addition of pembrolizumab to a
thalidomide analogue plus dexamethasone resulted in increased
mortality. Treatment of patients with MM with a PD-1 or PD-L1
blocking antibody in combination with a thalidomide analogue plus
dexamethasone is not recommended outside of controlled clinical
trials.
Hepatotoxicity: Hepatic failure, including fatal cases,
has occurred in patients treated with REVLIMID + dexamethasone.
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.
Severe Cutaneous Reactions: Severe cutaneous reactions
including Stevens-Johnson syndrome (SJS), toxic epidermal
necrolysis (TEN), and drug reaction with eosinophilia and systemic
symptoms (DRESS) 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. Consider
REVLIMID interruption or discontinuation for Grade 2-3 skin rash.
Permanently discontinue REVLIMID for Grade 4 rash, exfoliative or
bullous rash, or for other severe cutaneous reactions such as SJS,
TEN, or DRESS.
Tumor Lysis Syndrome (TLS): Fatal instances of TLS have
been reported during treatment with REVLIMID. The patients at risk
of TLS are those with high tumor burden prior to treatment. Closely
monitor patients at risk and take appropriate preventive
approaches.
Tumor Flare Reaction (TFR): TFR has occurred during
investigational use of REVLIMID for CLL and lymphoma. Monitoring
and evaluation for TFR is recommended in patients with MCL, FL, or
MZL. Tumor flare may mimic the progression of disease (PD). In
patients with Grade 3 or 4 TFR, it is recommended to withhold
treatment with REVLIMID until TFR resolves to ≤Grade 1. REVLIMID
may be continued in patients with Grade 1 and 2 TFR without
interruption or modification, at the physician’s discretion.
Impaired Stem Cell Mobilization: A decrease in the number
of CD34+ cells collected after treatment (>4 cycles) with
REVLIMID has been reported. Consider early referral to transplant
center to optimize timing of the stem cell collection.
Thyroid Disorders: Both hypothyroidism and
hyperthyroidism have been reported. Measure thyroid function before
starting REVLIMID treatment and during therapy.
Early Mortality in Patients With MCL: In another MCL
study, there was an increase in early deaths (within 20 weeks);
12.9% in the REVLIMID arm versus 7.1% in the control arm. Risk
factors for early deaths include high tumor burden, MIPI score at
diagnosis, and high WBC at baseline (≥10 x 109/L).
Hypersensitivity: Hypersensitivity, including angioedema,
anaphylaxis, and anaphylactic reactions to REVLIMID has been
reported. Permanently discontinue REVLIMID for angioedema and
anaphylaxis.
ADVERSE REACTIONS
Multiple Myeloma
- In newly diagnosed: The most frequently reported Grade 3
or 4 reactions included neutropenia, anemia, thrombocytopenia,
pneumonia, asthenia, fatigue, back pain, hypokalemia, rash,
cataract, lymphopenia, dyspnea, DVT, hyperglycemia, and leukopenia.
The highest frequency of infections occurred in Arm Rd Continuous
(75%) compared to Arm MPT (56%). There were more Grade 3 and 4 and
serious adverse reactions of infection in Arm Rd Continuous than
either Arm MPT or Rd18.
- The most common adverse reactions reported in ≥20% (Arm Rd
Continuous): diarrhea (45%), anemia (44%), neutropenia (35%),
fatigue (33%), back pain (32%), asthenia (28%), insomnia (28%),
rash (26%), decreased appetite (23%), cough (23%), dyspnea (22%),
pyrexia (21%), abdominal pain (20%), muscle spasms (20%), and
thrombocytopenia (20%).
- Maintenance Therapy Post Auto-HSCT: The most frequently
reported Grade 3 or 4 reactions in ≥20% (REVLIMID arm) included
neutropenia, thrombocytopenia, and leukopenia. The serious adverse
reactions of lung infection and neutropenia (more than 4.5%)
occurred in the REVLIMID arm.
- The most frequently reported adverse reactions in ≥20%
(REVLIMID arm) across both maintenance studies (Study 1, Study 2)
were neutropenia (79%, 61%), thrombocytopenia (72%, 24%),
leukopenia (23%, 32%), anemia (21%, 9%), upper respiratory tract
infection (27%, 11%), bronchitis (4%, 47%), nasopharyngitis (2%,
35%), cough (10%, 27%), gastroenteritis (0%, 23%), diarrhea (54%,
39%), rash (32%, 8%), fatigue (23%, 11%), asthenia (0%, 30%),
muscle spasm (0%, 33%), and pyrexia (8%, 20%).
- After at least one prior therapy: The most common
adverse reactions reported in ≥20% (REVLIMID/dex vs dex/placebo):
fatigue (44% vs 42%), neutropenia (42% vs 6%), constipation (41% vs
21%), diarrhea (39% vs 27%), muscle cramp (33% vs 21%), anemia (31%
vs 24%), pyrexia (27% vs 23%), peripheral edema (26% vs 21%),
nausea (26% vs 21%), back pain (26% vs 19%), upper respiratory
tract infection (25% vs 16%), dyspnea (24% vs 17%), dizziness (23%
vs 17%), thrombocytopenia (22% vs 11%), rash (21% vs 9%), tremor
(21% vs 7%), and weight decreased (20% vs 15%).
Myelodysplastic Syndromes
- Grade 3 and 4 adverse events reported in ≥ 5% of patients with
del 5q MDS were neutropenia (53%), thrombocytopenia (50%),
pneumonia (7%), rash (7%), anemia (6%), leukopenia (5%), fatigue
(5%), dyspnea (5%), and back pain (5%).
- Adverse events reported in ≥15% of del 5q MDS patients
(REVLIMID): thrombocytopenia (61.5%), neutropenia (58.8%), diarrhea
(49%), pruritus (42%), rash (36%), fatigue (31%), constipation
(24%), nausea (24%), nasopharyngitis (23%), arthralgia (22%),
pyrexia (21%), back pain (21%), peripheral edema (20%), cough
(20%), dizziness (20%), headache (20%), muscle cramp (18%), dyspnea
(17%), pharyngitis (16%), epistaxis (15%), asthenia (15%), upper
respiratory tract infection (15%).
Mantle Cell Lymphoma
- Grade 3 and 4 adverse events reported in ≥5% of patients
treated with REVLIMID in the MCL trial (N=134) included neutropenia
(43%), thrombocytopenia (28%), anemia (11%), pneumonia (9%),
leukopenia (7%), fatigue (7%), diarrhea (6%), dyspnea (6%), and
febrile neutropenia (6%).
- Adverse events reported in ≥15% of patients treated with
REVLIMID in the MCL trial included neutropenia (49%),
thrombocytopenia (36%), fatigue (34%), anemia (31%), diarrhea
(31%), nausea (30%), cough (28%), pyrexia (23%), rash (22%),
dyspnea (18%), pruritus (17%), peripheral edema (16%), constipation
(16%), and leukopenia (15%).
Follicular Lymphoma/Marginal Zone Lymphoma
- Fatal adverse reactions occurred in 6 patients (1.5%) receiving
REVLIMID + rituximab across both trials. Fatal adverse reactions (1
each) included: cardio-respiratory arrest, arrhythmia,
cardiopulmonary failure, multiple organ dysfunction syndrome,
sepsis, and acute kidney injury. The most frequent serious adverse
reaction that occurred in the REVLIMID + rituximab arm was febrile
neutropenia (3.0%).
- Grade 3 and 4 adverse reactions reported in ≥5% of patients
treated in the FL/MZL trial with REVLIMID + rituximab were:
neutropenia (50%) and leukopenia (7%).
- Adverse reactions reported in ≥15% of patients with FL/MZL
treated with REVLIMID + rituximab were: neutropenia (58%), diarrhea
(31%), constipation (26%), cough (24%), fatigue (22%), rash (22%),
pyrexia (21%), leukopenia (20%), pruritus (20%), upper respiratory
tract infections (18%), abdominal pain (18%), anemia (16%),
headache (15%), thrombocytopenia (15%).
DRUG INTERACTIONS
Periodically monitor digoxin plasma levels due to increased Cmax
and AUC with concomitant REVLIMID therapy. Patients taking
concomitant therapies such as erythropoietin-stimulating agents or
estrogen-containing therapies may have an increased risk of
thrombosis. It is not known whether there is an interaction between
dexamethasone and warfarin. Close monitoring of PT and INR is
recommended in patients with MM taking concomitant warfarin.
USE IN SPECIFIC POPULATIONS
- Pregnancy: See Boxed WARNINGS: If pregnancy does occur
during treatment, immediately discontinue the drug and refer
patient to an obstetrician/gynecologist experienced in reproductive
toxicity for further evaluation and counseling. There is a REVLIMID
pregnancy exposure registry that monitors pregnancy outcomes in
females exposed to REVLIMID during pregnancy as well as female
partners of male patients who are exposed to REVLIMID. This
registry is also used to understand the root cause for the
pregnancy. Report any suspected fetal exposure to REVLIMID to the
FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene
Corporation at 1-888-423-5436.
- Lactation: There is no information regarding the
presence of lenalidomide in human milk, the effects of REVLIMID on
the breastfed infant, or the effects of REVLIMID on milk
production. Because many drugs are excreted in human milk and
because of the potential for adverse reactions in breastfed infants
from REVLIMID, advise female patients not to breastfeed during
treatment with REVLIMID.
- Renal Impairment: Adjust the starting dose of REVLIMID
based on the creatinine clearance value and for patients on
dialysis.
Please see full Prescribing Information, including Boxed
WARNINGS, for REVLIMID.
For more information, please see the full SMPC related to the
EC approval.
Please see the rituximab full Prescribing Information for
Important Safety Information at www.rituxan.com.
About Bristol-Myers
Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose
mission is to discover, develop and deliver innovative medicines
that help patients prevail over serious diseases. For more
information about Bristol-Myers Squibb, visit us at BMS.com or
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Instagram.
Cautionary Statement Regarding
Forward-Looking Statements
This press release contains “forward-looking statements” within
the meaning of the Private Securities Litigation Reform Act of 1995
regarding, among other things, the research, development and
commercialization of pharmaceutical products. All statements that
are not statements of historical facts are, or may be deemed to be,
forward-looking statements. Such forward-looking statements are
based on historical performance and current expectations and
projections about our future financial results, goals, plans and
objectives and involve inherent risks, assumptions and
uncertainties, including internal or external factors that could
delay, divert or change any of them in the next several years, that
are difficult to predict, may be beyond our control and could cause
our future financial results, goals, plans and objectives to differ
materially from those expressed in, or implied by, the statements.
These risks, assumptions, uncertainties and other factors include,
among others, that the outcome of pricing and reimbursement
negotiations in individual countries in Europe may delay or limit
the commercial potential of Revlimid (lenalidomide), in combination
with rituximab (anti-CD20 antibody), for the additional indication
described in this release and whether Revlimid (lenalidomide), in
combination with rituximab (anti-CD20 antibody), for such
additional indication described in this release will be
commercially successful. No forward-looking statement can be
guaranteed. Forward-looking statements in this press release should
be evaluated together with the many risks and uncertainties that
affect Bristol-Myers Squibb’s business and market, particularly
those identified in the cautionary statement and risk factors
discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for
the year ended December 31, 2018, as updated by our subsequent
Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and
other filings with the Securities and Exchange Commission. The
forward-looking statements included in this document are made only
as of the date of this document and except as otherwise required by
applicable law, Bristol-Myers Squibb undertakes no obligation to
publicly update or revise any forward-looking statement, whether as
a result of new information, future events, changed circumstances
or otherwise.
_______________________________ 1 Scott DW, Gascoyne RD. The
tumour microenvironment in B cell lymphomas. Nat Rev Cancer.
2014;14(8):517-534. 2 Kridel R, Sehn LH, Gascoyne RD. Pathogenesis
of follicular lymphoma. J Clin Invest. 2012;122(10):3424-3431. 3
Chiu H, Trisal P, Bjorklund C, et al. Combination
lenalidomide-rituximab immunotherapy activates anti-tumour immunity
and induces tumour cell death by complementary mechanisms of action
in follicular lymphoma. Br J Haematol. 2019;185(2):240-253. 4
Revlimid Summary of Product Characteristics. Available at
https://www.ema.europa.eu/en/documents/product-information/revlimid-epar-product-information_en.pdf.
Accessed December 2019 5 ClinicalTrials.gov Lenalidomide Plus
Rituximab Followed by Lenalidomide Versus Rituximab Maintenance for
Relapsed/Refractory Follicular, Marginal Zone or Mantle Cell
Lymphoma (MAGNIFY). Available at:
https://clinicaltrials.gov/ct2/show/NCT01996865 Accessed August
2019. 6 American Cancer Society. Lymphoma. Available at:
https://www.cancer.org/cancer/lymphoma.html. Accessed August 2019.
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https://www.cancer.org/cancer/hodgkin-lymphoma/about/what-is-hodgkin-disease.html.
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