See other indications for REVLIMID:

This website is intended for U.S. Healthcare Professionals.

Indication Prescribing Information

This website is intended for U.S. Healthcare Professionals.

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 not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials.

Rd Continuous prolonged OS vs a non-REVLIMID triplet, MPT.1

(Secondary endpoint)

The FIRST Trial is a randomized, multicenter, open-label, 3-arm study that enrolled more than 1600 newly diagnosed patients who did not receive a stem cell transplant (SCT).

See the FIRST Trial Study Design

10.4-month increase vs MPT in an interim analysis.1

MEDIAN OS

  • OS was a pre-specified secondary endpoint, and the interim analysis did not show a statistically significant difference between these two arms
  • The median follow-up time for all surviving patients in the interim OS analysis was 45.5 months (data cutoff: Mar 3, 2014). In that time, 78% of pre-specified events required for the planned final OS analysis (697 death events) were reported

Rd Continuous extended PFS (primary endpoint).1

  • Median PFS: 25.5 months (95% CI 20.7, 29.4) with Rd Continuous vs 21.2 months (95% CI 19.3, 23.2) with MPT (HR 0.72; 95% CI 0.61, 0.85; P<0.0001)

FIRST Trial.1

FIRST Trial (MM-020) was a randomized, multicenter, open-label, 3-arm study that enrolled over 1600 patients evaluating REVLIMID + dex (Rd) until progression or unacceptable toxicity, in newly diagnosed patients who did not receive an auto-HSCT. Patients were ≥65 years or <65 years and were not a candidate for SCT if the patient refused or did not have access to auto-HSCT. Patients were stratified by age, stage, and country.3

STUDY DESIGN (N=1623)1

REVLIMID® + dexamethasone FIRST Trial
  • Primary endpoint was PFS
  • The primary comparison for efficacy was between the Rd Continuous and MPT arms
  • Secondary endpoints included OS and response rates
  • All patients received prophylactic anticoagulation, with the most commonly used being aspirin
  • The dose of REVLIMID in the clinical trial was 25 mg orally once daily on Days 1 to 21 of repeated 28-day cycles with low-dose oral dex on Days 1, 8, 15, and 22
    • The dose for dex was 40 mg orally for patients ≤75 years or 20 mg orally for patients >75 years
    • Initial dose and regimens for Rd Continuous and Rd18 were adjusted by age and renal function
  • OS was defined as the time from randomization to death from any cause. NE included patients with no response assessment and those whose only assessment was “response not evaluable.”1
  • PFS was defined as the time from randomization to the first documentation of disease progression as determined by IRAC, based on IMWG response criteria, or death due to any cause, whichever occurred first during the study until the end of the PFS follow-up phase.1 The data cutoff was May 24, 2013.

MANY PATIENTS IN THE FIRST TRIAL WERE >75 YEARS OLD OR HAD RENAL IMPAIRMENT.1,2

%

>75 years of age

Median age of 73 years (range 40-92)

%

Moderate to severe renal impairment

(CrCl ≤50 mL/min, excluding patients on dialysis)

Demographics and disease-related baseline characteristics of patients were balanced across study arms.1-3

REVLIMID® + dexamethasone Baseline Characteristics
  • auto-HSCT, autologous hematopoietic stem cell transplantation; CI, confidence interval; CrCl, creatinine clearance; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; IMWG, International Myeloma Working Group; IRAC, Independent Response Adjudication Committee; ISS, International Staging System; MPT, melphalan + prednisone + thalidomide; NDMM, newly diagnosed multiple myeloma; NE, not evaluable; NSCT, non-stem cell transplant; OS, overall survival; PFS, progression-free survival; Rd, REVLIMID + dexamethasone; SCT, stem cell transplant.

References: 1. REVLIMID [package insert]. Summit, NJ: Celgene Corp. 2. Benboubker L, Dimopoulos MA, Dispenzieri A, et al. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014;371(10):906-917. 3. Data on file. Celgene Corp; 2020.

Rd safety profile.

View Rd Safety

INDICATIONS

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 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, Lenalidomide REMS.

INDICATION FOR REVLIMID + DEXAMETHASONE + DARATUMUMAB (DRd)

DRd is indicated for the treatment of adult patients with newly diagnosed MM who are ineligible for an autologous stem cell transplant.

Information about DRd does not appear in the REVLIMID full Prescribing Information. Please see the daratumumab full Prescribing Information and Important Safety Information at www.darzalexhcp.com/iv.

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 Lenalidomide REMS program.

Information about the Lenalidomide REMS program is available at www.lenalidomiderems.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 (myelodysplastic syndromes) 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 (multiple myeloma) 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.

CONTRAINDICATIONS FOR DARATUMUMAB

Daratumumab is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the components of the formulation.

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 while taking REVLIMID and for up to 4 weeks after discontinuing REVLIMID.
  • 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.

Lenalidomide REMS Program: See Boxed WARNINGS. Prescribers and pharmacies must be certified with the Lenalidomide 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.

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. Erythropoietin-stimulating agents (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, including fatal reactions, have 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.

WARNINGS AND PRECAUTIONS FOR DARATUMUMAB

  • Infusion-related reactions: Daratumumab can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening and fatal outcomes have been reported. Interrupt daratumumab infusion for infusion-related reactions of any severity. Permanently discontinue the infusion in case of anaphylactic reactions or life-threatening infusion reactions and institute appropriate emergency care.
  • Interference with cross-matching and red blood cell antibody screening: Type and screen patients prior to starting treatment. Inform blood banks that a patient has received daratumumab.
  • Neutropenia: Monitor complete blood cell counts periodically during treatment. Monitor patients with neutropenia for signs of infection. Consider withholding daratumumab until recovery of neutrophils.
  • Thrombocytopenia: Monitor complete blood cell counts periodically during treatment. Consider withholding daratumumab until recovery of platelets.
  • Interference With Determination of Complete Response: Daratumumab can interfere with the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.
  • Embryo-Fetal Toxicity: Can cause fetal harm. Advise pregnant women of the potential risk to a fetus and advise females of reproductive potential to use effective contraception.

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%).

ADVERSE REACTIONS FOR DRd

  • In newly diagnosed: The most frequent (≥20%) adverse reactions (DRd arm) were: diarrhea (57%), upper respiratory tract infection (52%), infusion reactions (41%), constipation (41%), peripheral edema (41%), fatigue (40%), back pain (34%), nausea (32%), asthenia (32%), dyspnea (32%), cough (30%), bronchitis (29%), muscle spasms (29%), pneumonia (26%), peripheral sensory neuropathy (24%), pyrexia (23%), decreased appetite (22%).
  • Grade 3 or 4 hematology laboratory abnormalities (DRd arm) included: neutropenia (56%), lymphopenia (52%), leukopenia (35%), anemia (13%), thrombocytopenia (9%).

DRUG INTERACTIONS

Periodically monitor digoxin plasma levels due to increased Cmax and AUC with concomitant REVLIMID therapy. Patients taking concomitant therapies such as ESAs 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 REMS Call Center 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 women 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.

Please see the daratumumab full Prescribing Information and Important Safety Information at www.darzalexhcp.com/iv.

05/23 2003-US-2300024

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12/22    2003-US-2200263