View data from pivotal trial
See data supporting this new indication Having trouble viewing this email? View online
NOW INDICATED: R^2 (REVLIMID + RITUXIMAB)
REVLIMID® (lenalidomide) 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®.
WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and VENOUS and ARTERIAL THROMBOEMBOLISM
See full prescribing information for complete boxed warning.
Embryo-Fetal Toxicity
Lenalidomide, a thalidomide analogue, caused limb abnormalities in a developmental monkey study similar to birth defects caused by thalidomide in humans. If lenalidomide is used during pregnancy, it may cause birth defects or embryo-fetal death
Pregnancy must be excluded before start of treatment. Prevent pregnancy during treatment by the use of two reliable methods of contraception
REVLIMID is available only through a restricted distribution program called the REVLIMID REMS® program
HEMATOLOGIC TOXICITY. REVLIMID can cause significant neutropenia and thrombocytopenia.
Venous and Arterial Thromboembolism
Significantly increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as risk of myocardial infarction and stroke in patients with multiple myeloma receiving REVLIMID with dexamethasone. Anti-thrombotic prophylaxis is recommended
Please see additional Important Safety Information below and full Prescribing Information, including Boxed WARNINGS, for REVLIMID.
DEAR Amy​ Gonsuron​,
R2 (REVLIMID + rituximab) is a new combination immunotherapy approved for previously treated FL and MZL. Data below are results from the Phase III AUGMENT trial.1
/ R2 SIGNIFICANTLY IMPROVED MEDIAN PFS VS RITUXIMAB1
R^2 SIGNIFICANTLY IMPROVED MEDIAN PFS VS RITUXIMAB
IN THE FL SUBGROUP (n=295), THE MEDIAN PFS WAS 39.4 MONTHS (95% CI: [23.1, NE]) IN THE R2 ARM AND 13.9 MONTHS (95% CI: [11.2, 16.0]) WITH RITUXIMAB (HR AND 95% CI: 0.40 [0.29, 0.56])2
ANALYSIS LIMITATIONS: PFS in the FL subgroup is exploratory in nature and data should not be interpreted to determine a treatment difference between arms due to a higher possibility of a false positive
/ OVERALL SURVIVAL2*
Median OS has not been reached
OVERALL SURVIVAL
ANALYSIS LIMITATIONS: OS was a secondary endpoint. These FL subgroup data are exploratory in nature and should not be interpreted to determine a treatment difference between arms due to a higher possibility of a false positive
*OS was calculated as the time from randomization to death from any cause.2
Median follow-up time was 28.3 months (0.1, 51.3 months) in the ITT population.2
view additional data
/ PIVOTAL TRIAL DESIGN
AUGMENT, a Phase III, multicenter, randomized trial of lenalidomide plus rituximab (R2) versus rituximab plus placebo, was conducted in 358 patients with previously treated Grade 1-3a FL (n=295) or MZL (n=63). Patients had been refractory or relapsed, not rituximab-refractory, and had adequate bone marrow, liver, and renal function. The ITT population included all patients randomized to the R2 (n=178) and rituximab plus placebo (n=180) arms1,3
At baseline, patients had a median age of 63 years (range, 26-88) and had received a median of 1 prior line of systemic therapy (range, 1-12). Seventy-three percent (73%) of patients had Ann Arbor Stage III-IV disease1,3
The primary endpoint for the trial was PFS, defined as the time from date of randomization to first documentation of disease progression (by independent review committee using 2007 IWGRC without PET) or death due to any cause, whichever occurred first. Median follow-up time was 28.3 months (0.1, 51.3 months) in the ITT population2
The starting dose of REVLIMID was 20 mg orally on Days 1-21 of repeating 28-day cycles for 12 cycles or until unacceptable toxicity. The dose of rituximab was 375 mg/m2 on Days 1, 8, 15, and 22 of cycle 1 and on Day 1 of cycles 2 to 5 every 28 days1
/ SAFETY PROFILE
The most common (≥5%) Grade 3/4 adverse reactions in either arm were neutropenia (50% vs 13%), leukopenia (7% vs 2%), and anemia (5% vs <1%); REVLIMID/rituximab vs rituximab/placebo, respectively1
The most common (≥20%) adverse reactions in either arm were neutropenia (58% vs 22%), diarrhea (31% vs 23%), constipation (26% vs 14%), cough (24% vs 19%), fatigue (22% vs 18%), rash (22% vs 8%), pyrexia (21% vs 15%), leukopenia (20% vs 9%), and pruritus (20% vs 5%); REVLIMID/rituximab vs rituximab/placebo, respectively1
CI, confidence interval; HR, hazard ratio; ITT, intent to treat; IWGRC, International Working Group Response Criteria; NE, non-estimable; OS, overall survival; PET, positron emission tomographic imaging; PFS, progression-free survival.
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 (eg, 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 dose interruption and/or dose reduction. Monitor complete blood counts (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 (eg, 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 SPMs, notably AML, have been observed. In MM patients, 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 Including Hypersensitivity Reactions: Angioedema and 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. 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, TEN, or DRESS is suspected and should not be resumed following discontinuation for these reactions
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)
ADVERSE REACTIONS
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 creatinine clearance value and in patients on dialysis
 
Please see full Prescribing Information, including Boxed WARNINGS, for REVLIMID.
Please see the rituximab full Prescribing Information for Important Safety Information at rituxan.com.
References: 1. REVLIMID [package insert]. Summit, NJ: Celgene Corp; 2019. 2. Data on file. Celgene Corporation 3. Leonard JP, et al. J Clin Oncol. 2019;37(14):1188-1199. 
This email was sent by Celgene Corporation and is intended for US healthcare providers only.
Celgene Corporation, 86 Morris Avenue, Summit, New Jersey, 07901
To no longer receive these messages from Celgene about REVLIMID concerning follicular lymphoma, please click here to unsubscribe.
Click here to no longer receive any promotional emails from the Celgene Hematology/Oncology Franchise.
REVLIMID® and REVLIMID REMS® are registered trademarks of Celgene Corporation.
Other trademarks are property of their respective owners.
© 2019 Celgene Corporation  05/19  US-REV-19-0017

Contact Us  |  Privacy Policy  |  Terms of Use
Update Profile
click
This email was sent to amy.gonsuron@iononline.com because you have an account with or are a valued partner of ION Solutions. If you no longer wish to receive these types of emails, please click here to unsubscribe or update your email preferences.
AmerisourceBergen - 1300 Morris Dr Chesterbrook PA, 19087
© 2019 ION Solutions. All Rights Reserved.