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, an increase of hematologic plus solid tumor
SPM, notably AML and MDS have been observed. Monitor patients for the development of SPM. Take into account both the potential benefit of
REVLIMID and risk of SPM when considering treatment
Hepatotoxicity: Hepatic failure, including fatal cases, has occurred in patients treated with REVLIMID/dex. 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 treatment should be evaluated in patients
with lactose intolerance
Tumor Lysis Syndrome (TLS): Fatal instances of 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 (TFR): TFR has occurred during investigational use of lenalidomide for CLL and lymphoma. 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 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 start of REVLIMID
treatment and during therapy
• 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 (5%, 47%), nasopharyngitis (2%, 35%), cough (10%, 27%), gastroenteritis (0%, 23%), diarrhea (55%, 39%), rash (32%, 8%),
fatigue (23%, 11%), asthenia (0%, 30%), muscle spasm (0%, 33%), and pyrexia (8%, 21%)
Periodic monitoring of digoxin plasma levels is recommended 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 dex 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 Med Watch program at 1-800-FDA-1088 and also to Celgene Corporation
• 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
• PEDIATRIC USE: Safety and effectiveness have not been established in pediatric patients
• RENAL IMPAIRMENT: Adjust the starting dose of REVLIMID based on creatinine clearance value and in patients on dialysis
Please see Brief Summary of full Prescribing Information, including Boxed WARNINGS, on the following pages.
REVLIMID® and REVLIMID REMS® are registered trademarks of Celgene Corporation.
© 2017 Celgene Corporation 03/17 US-REV170010(1)
IMPORTANT SAFETY INFORMATION (CONTINUED)
1. Poon ML, Chng WJ. Is complete remission an important therapeutic aim in multiple myeloma? Cancer Ther. 2008;6:275-284.
2. Paiva B, Vidriales MB, Cervero J, et al. Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients
who undergo autologous stem cell transplantation. Blood. 2008;112(10):4017-4023.
3. REVLIMID [package insert]. Summit, NJ: Celgene Corp; 2017.
4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma V.3.2017.
©National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed January 23, 2017. To view the most recent and
complete version of the guideline, go online to NCCN.org.
5. Data on file. Celgene Corp; 2017.