 | | | Dear {{customText[Dr.|Mr.|Ms.|Mrs.|Prof.]}} {{accFname}} {{accLname}}, | | | | {{customText[Thank you for taking the time to meet with me. As a follow-up to our conversation, please find some data from the REVLIMID maintenance trials below. To watch a transplant specialist discuss these trials further, see the link below.|I'm sorry I missed you today! Below I've included some information on efficacy and safety data in two REVLIMID maintenance trials that I thought you might find helpful when choosing a treatment for your post auto-HSCT multiple myeloma patients. For more information about these data, check out a video of a transplant expert below. Please text or email me if you'd like to discuss further.|I would like to hear your thoughts on the efficacy and safety data from two maintenance trials included here next time we meet. After you review the data, watch a transplant expert dive into these data through the link below, and please text or email me if you'd like to discuss further.|I’ve included some efficacy and safety data from two pivotal REVLIMID maintenance studies that I think might be helpful when deciding on a treatment for your post auto-HSCT multiple myeloma patients. For more information, watch a transplant expert discuss these data through the link below. I look forward to hearing your thoughts the next time we meet.]}} | | | | Best regards, | | | | {{userName}} | | | | Celgene Consultant | | | | {{User.Phone}} | | | REVLIMID contains Boxed Warnings for EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and VENOUS and ARTERIAL THROMBOEMBOLISM.
See additional Important Safety Information below. | | | REVLIMID is the ONLY
FDA-approved
MM maintenance
therapy post auto-HSCT,2 | | | | | | MEDIAN PFS: 3.8 YEAR INCREASE VS PLACEBO IN CALGB (STUDY 1)2 |  |  | | (HR 0.75; 95% CI 0.62, 0.90) | | | | | | |  | 1.9‐YEAR ADVANTAGE
IN MEDIAN PFS
VS PLACEBO IN IFM (STUDY 2)2 | | |
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| | | | | | | | Median PFS: 3.9 years with REVLIMID Maintenance (95% CI 3.3, 4.7) (n=307) vs 2.0 years with placebo (95% CI 1.8, 2.3) (n=307) (HR 0.53 [95% CI 0.44, 0.64]) | | | | Updated analysis from March 2015, based on ITT population. | | | | | | | | MEDIAN OS DESCRIPTIVE ANALYSIS2 | | |  |  | | Descriptive analysis of overall survival data with a cutoff of February 1, 2016. Median follow-up time was 81.6 months for CALGB (Study 1) and 96.7 months for IFM (Study 2). Neither CALGB (Study 1) nor IFM (Study 2) was powered to evaluated OS. | | | | Trial Design: | CALGB (Study 1) and IFM (Study 2) were multicenter, randomized, double-blind, parallel-group, placebo-controlled studies in newly diagnosed patients 18-70 years (CALGB) and <65 years at diagnosis (IFM) who received auto-HSCT following induction therapy, which must have occurred within 12 months. Patients were randomized 1:1 to receive REVLIMID or placebo maintenance 90-100 days (CALGB) or within 6 months (IFM) post auto-HSCT. Patients were required to achieve at least stable disease following hematologic recovery and CrCl ≥30 mL/min. The primary endpoint for both studies was PFS, based on assessment by investigator, and was defined from randomization to the date of progression or death, whichever occurred first. In both studies, the starting dose of REVLIMID was 10 mg once daily for repeated 28-day cycles. If tolerated after 3 months, a dose increase to 15 mg once daily occurred in 135 patients (58%) in CALGB, and 185 patients (60%) in IFM.
The dose was reduced, interrupted, and/or discontinued as needed to manage toxicity. Patients were treated until disease progression, unacceptable toxicity, or patient withdrawal for any reason. At a preplanned interim analysis, the primary endpoint of PFS was met and both studies were unblinded and patients continued to be followed as before. Patients in the placebo arm of CALGB were allowed to cross over to receive Revlimid before disease progression; patients in the IFM study were not recommended to cross over. In IFM, REVLIMID was stopped at the recommendation of the Data Monitoring Committee in January 2011. | | | | Selected Safety Information | | | | ADVERSE REACTIONS | | | | Multiple Myeloma | | | | • | 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%). |
| | | | Please see additional Important Safety Information below. | | |  | Watch Dr Randolph discuss
REVLIMID maintenance therapy |  |
| | | auto-HSCT, autologous hematopoietic stem cell transplantation;
CALGB, Cancer and Leukemia Group B;
CrCl, creatinine clearance;
HR, hazard ratio; IFM, IFM Therapeutics, LLC; ITT, intent-to-treat;
NE, not evaluable;
PFS, progression-free survival; OS, overall survival. | | | | Indications | | | | REVLIMID® (lenalidomide) is indicated as maintenance therapy in adult patients with multiple myeloma (MM) following autologous hematopoietic stem cell transplantation (auto-HSCT). | | | | 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®. | | |
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| | | | | | | | | | 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. | | |
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| | | | 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 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. | | | | 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 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 | | | | Multiple Myeloma | | | | • | 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%). |
| | | | 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. | | | | REFERENCES: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma V.3.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed June 24, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. 2. REVLIMID [package insert]. Summit, NJ: Celgene Corp; 2019 |
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| | | | | 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 opt out of Celgene messages about REVLIMID® and/or multiple myeloma, and/or to unsubscribe from all other promotional emails from Celgene Hematology/Oncology click here. | | | | REVLIMID® and REVLIMID REMS® are registered trademarks of Celgene Corporation. | | | | © 2019 Celgene Corporation | | 07/19 | | US-REV-19-0302 |
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| | | 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 opt out of Celgene messages about REVLIMID® and/or multiple myeloma, and/or to unsubscribe from all other promotional emails from Celgene Hematology/Oncology click here. | | | | REVLIMID® and REVLIMID REMS® are registered trademarks of Celgene Corporation. | | | © 2019 Celgene Corporation
07/19 US-REV-19-0302 |
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