Understanding
Revlimid®
International Myeloma Foundation
12650 Riverside Drive, Suite 206
North Hol ywood, CA 91607 USA
Telephone:
800-452-CURE (2873)
(USA & Canada)
818-487-7455
Fax: 818-487-7454
TheIMF@myeloma.org
www.myeloma.org
Table of Contents
Introduction
5
What is Revlimid® and
How Does it Work?
6
Use of Revlimid® as Maintenance
in the Post-Transplant Setting
9
What are the Possible Side Effects
of Revlimid®?
11
Other Side Effects to be Aware of
When Revlimid® is Combined
with Dexamethasone
16
Dose Adjustments with Revlimid®
17
Will a Dose Reduction in Revlimid®
Change the Effectiveness of Treatment?
18
How is Revlimid® Given?
18
About the IMF
19
Glossary
26
©2011, International Myeloma Foundation, North Hollywood, California (IV11)
Introduction
You have been given this booklet to learn
more about a new drug cal ed Revlimid®
(lenalidomide). After reading this booklet
you should know:
n What Revlimid® is
n How Revlimid® works
n The possible side ef ects of Revlimid®
n How Revlimid® is given
This booklet is meant to provide you with
general information only. It is not meant to
replace the advice of your doctor or nurse.
Your doctor or nurse can answer questions
related to your specific treatment plan. Al
words that appear in bold type are defined
in the glossary at the end of the booklet.
Multiple myeloma is a serious malignancy,
but it is treatable. Many patients experience
a series of responses, relapses, and remis-
sions. With new treatments, the average
survival of 5 years for patients diagnosed
with multiple myeloma may be extended. A
significant number of patients are living 10
and even 20 or more years with the disease.
Fol owing diagnosis, several options are
available for initial or front-line therapy.
Various induction regimens can be consid-
ered, both for patients who are candidates
for high-dose chemotherapy with stem cel
transplant and those who are not. (see the
IMF's Patient Handbook). At relapse, newer
agents are frequently required to achieve
4
5
further response. Revlimid is an important
including the ability to induce programmed
novel agent for use in this set ing.
cel death of myeloma cel s, inhibit myeloma
cel growth, inhibit new blood vessel growth,
and reduce adhesion of myeloma cel s
What is Revlimid® and
to bone marrow stromal cel s. Moreover,
How Does it Work?
Revlimid® can act synergistical y with other
Revlimid® is an immunomodulatory agent.
antimyeloma agents and kil myeloma cel s
It is a drug that can modify or regulate the
that are resistant to conventional therapy.
functioning of the immune system. These
Clinical studies are investigating the ef ects
agents appear to have multiple actions,
of Revlimid® on myeloma in newly diag-
including both anticancer and anti-inflam-
nosed patients and on in patients with
matory
activities.
Immunomodulatory
relapsed and refractory myeloma. Clinical
agents induce immune responses, enhance
trials are also studying the use of Revlimid®
the activity of immune cel s, and inhib-
for maintenance therapy.
it inflammation. They are able to alter
Based on the data from two pivotal Phase
the levels of various growth factors, cal ed
I I clinical trials of Revlimid® and high-dose
cytokines
and/or
interleukins,
and
dexamethasone versus high-dose dexameth-
affect cel s of the immune system.
asone alone in patients with relapsed or
Immunomodulatory agents enhance the acti-
refractory myeloma, in June 2006, the FDA
vation of specialized white blood cel s of the
approved Revlimid® in combination with
immune system both the T-cel lymphocytes
dexamethasone for use in patients who have
and T cel s known as natural kil er cel s, or
had at least one prior therapy. This relapse
NK-cel s which help kil cancer cel s.
set ing approval is the norm for most coun-
Revlimid® is a vascular endothelial growth
tries, with specifics varying from country to
factor inhibitor. It belongs to a group of
country.
immunomodulatory agents with the ability
In both of these Phase I I trials, patients treat-
to inhibit new blood vessel development on
ed with the combination of Revlimid® and
which cancer cel s depend. Revlimid® is
high-dose dexamethasone had an increase
structural y related to thalidomide but has
in side effects compared with patients receiv-
been modified by researchers to take advan-
ing high-dose dexamethasone alone. The
tage of the anticancer properties, and at the
side ef ects were general y manageable and
same time substantial y reduce the likelihood
included constipation, neutropenia, diar-
of nerve or neurologic toxic side ef ects
rhea, thrombocytopenia, rash, fatigue, and
(peripheral neuropathy). Revlimid® has
deep vein thrombosis (blood clot).
direct and indirect ef ects on myeloma cel s,
6
7
Additional findings for Revlimid® and
newly-diagnosed Myeloma
Revlimid® was reported to be ef ective in
newly-diagnosed multiple myeloma in two
Mayo Clinic trials in 2005 and 2007. (see
E4A03, above). Currently there are many
ongoing trials of Revlimid®, alone and in
combination, in newly-diagnosed myeloma
in the US and Europe.
In addition, Revlimid® is being investigated
in various combinations, such as melphalan
plus prednisone (MPR); Velcade® (bortezo-
mib) plus low-dose dexamethasone (VRd),
cyclophosphomide and dexamethasone
(RCD), and Adriamycin and dexamethasone
(RAD).
Current National Comprehensive Cancer
Findings in support of low-dose Dexamethasone
Network (NCCN) Clinical Practice Guidelines
Many oncologists are now prescribing dexa-
in Oncology for Multiple Myeloma include
methasone in a once-weekly cycle, often at a
Revlimid®/dexamethasone as primary induc-
dose lower than 40 mg. Based upon ECOG
tion therapy for transplant candidates (cat-
trial E4A03, which compared Revlimid®
egory 1, or "recommendation based upon
plus standard high-dose dexamethasone ver-
high-level evidence, e.g., randomized, con-
sus Revlimid® plus low-dose dexamethasone
trol ed trials, and there is uniform NCCN
(40 mg once weekly), the once-weekly dos-
consensus"), and Revlimid®/low-dose dexa-
ing schedule is now the preferred approach.
methasone as primary induction therapy for
The ECOG trial evaluated the Revlimid/
non-transplant candidates (category 1).
dexamethasone (high- and low-dose) com-
binations in the frontline set ing. The once
Use of Revlimid® as Maintenance
per week schedule "low-dose" proved to
be more ef ective (bet er survival at 1 year)
in the Post-Transplant Setting
and had significantly fewer side ef ects. Your
At the annual meeting of the American
doctor wil work with you to find a dosing
Society of Hematology (ASH) in December
schedule that is wel tolerated and appropri-
2010, two large randomized trials evaluat-
ate to treat your multiple myeloma.
ing Revlimid® as a maintenance therapy after
8
9
high-dose melphalan with autologous stem
What are the Possible Side Effects
cel transplant were presented. Results from
of Revlimid®?
both trials, IFM 005 and the CALGB, were
very promising, with remissions twice as long
Most of the side ef ects associated with
with Revlimid® versus placebo (Progression
Revlimid® are manageable and predictable.
Free Survival - PFS of 42 months versus 21
The most important side ef ects are described
months). Further fol ow-up is necessary to
here. Your doctor or nurse can provide more
assess overal survival benefit. Based upon
information in greater detail about these and
the results of the further fol ow-up in these
other possible side ef ects.
pivotal trials, treating physicians wil be able
In clinical trials conducted to date, Revlimid®
to make appropriate recommendations con-
has a dif erent safety profile from thalido-
cerning this treatment decision.
mide. Significant sleepiness, constipation, or
The NCCN includes Revlimid® as an option
neuropathy common side ef ects seen with
for post-transplant maintenance therapy, but
thalidomide therapy are much less frequent.
in category 2A, which means that results
Animal studies conducted earlier showed evi-
of clinical trials have not yet undergone ful
dence that Revlimid® caused the same type
peer review; and that the safety and ef icacy
of severe birth defects as those in the past
data are stil preliminary.
with thalidomide. A risk-management plan
cal ed RevAssist is designed to prevent expo-
sure during pregnancy. With RevAssist, only
registered pharmacists and clinicians can
prescribe and dispense Revlimid®. The plan
requires patients, including female patients of
child-bearing potential, to undergo manda-
tory pregnancy testing, and to give informed
consent before taking Revlimid®. Female
patients of child-bearing potential and al
male patients are required to complete a
monthly phone survey. Clinicians must check
pregnancy tests, limit prescriptions to a
28-day mail supply, and report any pregnan-
cies to the FDA.
Safety information about Revlimid® is derived
from clinical trials, and as many clinical trials
10
11
are ongoing, no definitive conclusions can yet
be made. The events that have been observed
are listed below, from most frequent to
least frequent.
· Constipation
· Neutropenia
· Diarrhea
· Thrombocytopenia
· Rash
· Fatigue
· Deep-vein thrombosis (DVT)
In the prescribing information for Revlimid
(March 2010) the Black Box Warnings
include: the risk of birth defects or death to
a developing baby; the risks of neutropenia
and thrombocytopenia; and the increased
Management may include platelet transfu-
risk of deep vein thrombosis and pulmonary
sions at the discretion of your physician.
embolism (the lat er a blood clot that travels
to the lung).
Decreased White Blood Cel Levels neutropenia
Patients taking Revlimid® may experience
Remember, speak with your doctor or nurse
a condition cal ed neutropenia: a lowered
if you notice any changes in your health.
level of white cel s (neutrophils) in the blood.
Decreased Platelet Levels thrombocytopenia
Neutrophils help blood to fight infection;
Patients taking Revlimid® may experience a
fewer neutrophils can lead to a "cold" with
condition cal ed thrombocytopenia: a low-
fever, sore throat, and mouth sores.
ered level of platelets in the blood. Platelets
Prevention and Treatment of Decreased White
help blood to clot; fewer platelets can lead
Blood Cel Levels
to bruising, bleeding, and slower healing.
You should inform your physician if you
Prevention and Treatment of Decreased Platelet
experience fever, sore throat, or mouth sores.
Levels
Fever is the symptom that usual y indicates
You should inform your physician if you
infection in a person who has neutrope-
experience excessive bruising or bleeding.
nia. It is an important sign that immediate
medical at ention is needed. The treatment of
12
13
neutropenia depends on its cause and sever-
The ef ects of fatigue may be minimized by
ity. Sometimes the bone marrow recovers
maintaining:
by itself without treatment. The neutropenia
n A moderate level of activity
accompanying viral infections (such as influ-
n A healthy diet and proper fluid intake
enza) may be transient and resolve after
the infection has cleared. Mild neutropenia
n A consistent sleeping schedule with
general y has no symptoms and may not
enough rest
need treatment.
n Regularly scheduled visits with your
Fatigue
doctor or health-care provider to
Fatigue is commonly associated with Revlimid®
discuss fatigue issues
therapy. Although fatigue is general y not
Deep Vein Thrombosis
severe, caution is advised if you are operating
Deep vein thrombosis (DVT) is a serious condi-
machinery, including automobiles.
tion and is potential y life threatening. DVT is a
Prevention and Treatment of Fatigue
blood clot in a deep vein of the lower extremi-
Management of fatigue may include support-
ties (usual y occuring in the leg or thigh, and
ive care as determined by your physician.
very occasional y in the neck or upper arm). A
blood clot from a DVT can break loose (emboli-
ze) and travel to the heart or lungs. An embolus
is very dangerous. If you start taking Revlimid®
and experience warmth, swel ing, redness,
dif iculty breathing, and/or pain in an extrem-
ity, notify your doctor as soon as possible.
Prevention and Treatment of DVT
You are strongly advised to contact your
physician if you experience swel ing and/or
redness and/or pain in a leg or thigh. Your
doctor wil diagnose your condition to deter-
mine whether or not it is a DVT. Treatment of
a DVT may depend upon both its location
and underlying cause. Your doctor may pre-
scribe a blood thinner to keep the clot from
get ing larger.
14
15
Rash
Steroids, available from the IMF. Remember
Rash is a serious concern. It is potential y
to discuss any changes in your health with
dangerous, as a rash may be mild initial y
a doctor or nurse on your healthcare team.
and then escalate in severity. Drug rashes
vary in severity from mild redness with tiny
Dose Adjustments with Revlimid®
bumps over a smal area to peeling of the
entire skin. Rashes may appear suddenly
The standard dose for Revlimid® is 25 mg
within minutes after a person takes a drug,
each day for 21 days of a 28-day (one
or they may be delayed for hours or days.
month) cycle. After 3-6 months of use, your
physician may consider reducing the dose
Prevention and Treatment of Rash
because of lowered white and/or red blood
You are strongly urged to notify your doctor if
cel counts. In addition, there may be cumula-
you experience any rash. Proper evaluation
tive side effects such as fatigue or even slight
of a skin rash requires a visit to a doctor or
neuropathy. Your physician may decide that
other healthcare professional. If detected and
dose reduction is appropriate, lowering first
managed appropriately, a rash is reversible.
to 15 mg, then to 10 mg, and even to 5 mg
if necessary.
Other Side Effects to be Aware of
Ongoing results from clinical trials show that
When Revlimid® is Combined with
with such dose reductions, treatment benefit
Dexamethasone
is retained. Long remissions were reported
in the MM-009 and -010 relapse trials and
The major studies mentioned above, indicat-
ing benefit of Revlimid® in the relapse set-
ting, used a combination of Revlimid® with
dexamethasone. It is important to be aware
that additional toxicities can occur with this
combination versus Revlimid® alone.
Side ef ects that may occur with Revlimid®
plus dexamethasone include muscle weak-
ness, anxiety, agitation, cardiac arrhythmias,
nausea, increased blood sugar, elevated
liver enzymes, and constipation and/or diar-
rhea. Ful details with regard to dexametha-
sone are discussed in a separate booklet,
Understanding Dexamethasone and Other
16
17
patients were able to continue treatment
About the IMF
beyond 10 months (with dose reductions)
and achieve extended benefit.
"One person can make a dif erence,
Two can make a miracle."
Will a Dose Reduction in Revlimid®
Brian D. Novis
Change the Effectiveness of
IMF Founder
Treatment?
Myeloma is a lit le-known, complex, and
It is important to communicate openly with
often misdiagnosed bone marrow cancer
your doctor or healthcare professional and
that at acks and destroys bone. Myeloma
keep regular appointments to maintain your
af ects approximately 75,000 to 100,000
people in the United States, with more than
Revlimid® treatment schedule. Your doctor
20,000 new cases diagnosed each year.
may choose to modify your dose of Revlimid®
Although there is presently no known cure for
as part of an overal plan to manage a par-
myeloma, doctors have many approaches to
ticular side ef ect that you experience. The
help myeloma patients live bet er and longer.
dose used in the Phase I I clinical studies is
25 mg per day. If you experience a severe
The International Myeloma Foundation (IMF)
side ef ect, your doctor may modify your
was founded in 1990 by Brian and Susie
dose in either amount or schedule to reduce
Novis shortly after Brian's myeloma diagno-
the severity of the side ef ect while maintain-
sis at the age of 33. It was Brian's dream
ing treatment.
that future patients would have easy access
to medical information and emotional sup-
How is Revlimid® Given?
port throughout their bat le with myeloma.
He established the IMF with the three goals
Revlimid® is given as capsules. The most
of treatment, education, and research. He
common dosing used in multiple myeloma is
sought to provide a broad spectrum of ser-
25 mg given oral y daily on days 121 and
vices for patients and, their families, friends,
repeated every 28 days (days 2228 are
and healthcare providers. Although Brian
rest days). Doses are then modified based
died four years after his initial diagnosis, his
on side ef ects.
dream did not. Today, the IMF reaches out
to an international membership of more than
IMF Hotline:
195,000. The IMF was the first organization
dedicated solely to myeloma, and today it
USA & Canada only: 800-452-CURE (2873)
remains the largest.
Elsewhere: 818-487-7455
The IMF provides programs and services to
IMF Web site: www.myeloma.org
aid in the research, diagnosis, treatment,
18
19
and management of myeloma. The IMF
MyELOMA MATRIxTM
ensures that no one must brave the myeloma
On our website and in print, this document is a
bat le alone.
comprehensive guide to drugs in development for
myeloma.
We care for patients today, while working
toward tomorrow's cure.
MyELOMA TODAyTM NEWsLETTER
Our quarterly newslet er is available free of
charge by subscription.
How Can the IMF Help You?
sUPPORT
PATIENT EDUCATION
MyELOMA HOTLINE: 800-452-CURE (2873)
INFORMATION PACkAgE
Tol -free throughout the United States and Canada,
Our free IMF InfoPackTM provides comprehensive
the IMF Hotline is staf ed by trained information
information about myeloma, treatment options,
specialists and is in frequent interaction with mem-
disease management, and IMF services. It
bers of our Scientific Advisory Board.
includes our acclaimed Patient Handbook.
sUPPORT gROUPs
INTERNET ACCEss
A worldwide network of more than 100 myeloma
Log on to www.myeloma.org for 24-hour access
support groups hold regular meetings for members
to information about myeloma, the IMF, educa-
of the myeloma community. The IMF conducts
tion, and support programs.
annual retreats for leaders of myeloma support
MyELOMA MANAgERTM PERsONAL CARE AssIsTANTTM
group leaders.
This software program was developed by the
IMF and is designed specifical y to help patients
REsEARCH
and caregivers to capture, display, and store
BANk ON A CURE®
laboratory test results, and to access important
This DNA bank wil provides genetic data research
information. It is available free of charge on the
in new drug development.
IMF website at www.myeloma.org. Currently this
program is only compatible with PCs.
THE INTERNATIONAL sTAgINg sysTEM (Iss)
This updated staging system for myeloma enhanc-
ONLINE MyELOMA FORUM
es physicians' ability to select the most appropri-
Join the IMF Internet Discussion Group at www.
ate treatment for each patient.
myeloma.org/listserve.html to share your thoughts
and experiences.
REsEARCH gRANTs
Leading the world in col aborative research and
MyELOMA MINUTETM
achieving extraordinary results, the IMF Grant
Subscribe to this free weekly email newslet er for
Program supports both junior and senior research-
up-to-the-minute information about myeloma.
ers working on a broad spectrum of projects.
The IMF has at racted many young investigators
IMF PATIENT & FAMILy sEMINARsTM
into the field of myeloma; they have remained
Meet with leading experts in myeloma treatment
in the field and are actively pursuing a cure for
to learn more about recent advances in therapy
this disease.
and research.
24
25
Glossary
Cytokine: A growth factor produced by T-cel s that stimu-
Thrombocytopenia: A low level of platelets in the blood.
lates the growth of T cel s and B cel s.
These low levels can cause bruising or bleeding as wel
Enzyme: A type of protein that causes chemical reactions
as delay in the injury healing process.
of other substances without undergoing change in the
Vascular endothelial growth factor (VEGF): A growth factor
process.
that promotes the growth of new blood vessels (angio-
Febrile neutropenia: Presence of a low neutrophil count in
genesis).
the blood that is associated with fever; may indicate the
White blood cell: A cel made by the bone marrow that
presence of infection.
helps fight infection and/or disease.
Immunomodulatory agent: Drug that af ects, enhances, or
suppresses the immune system.
Interleukin: Various cytokines involved in the growth and
survival of myeloma cel s.
Lymphocyte: A type of white blood cel , mainly B-cel s
that produce immunoglobulins and T-cel s that produce
cytokines and interleukins. Also includes natural kil er cel s
(NK-cel ). A type of lymphocyte with enzymes that can kil
tumor cel s or microbial cel s.
Multiple myeloma: A cancer arising from the plasma cel s
in the bone marrow. The plasma cel s in patients with
multiple myeloma form abnormal antibodies, possibly
damaging the bone, bone marrow and other organs.
Neutrophil: A white blood cel .
Neutropenia: A low level of white blood cel s in the
bloodstream.
Peripheral neuropathy: Numbness, tingling, and/or pain in
the hands, feet, legs, and/or arms.
Platelet: An element in the blood that helps with clot ing,
which in turn helps repair damaged blood vessels.
Red blood cell: A blood cel that carries oxygen from the
lungs throughout the body.
Side effect: An ef ect caused by the treatment with a drug.
The term usual y refers to an unwanted ef ect, but some
side ef ects may be beneficial.
Stromal cell: Structural cel s of the bone marrow that help
support and nourish the blood-producing cel s.
26
27