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EMPLICITI® (elotuzumab) is indicated for the treatment of adult patients with multiple myeloma in combination with:
Please see below for Indications and Important Safety Information.
Bristol Myers Squibb is committed to helping appropriate patients initiate and maintain access to our medications during the treatment journey.
References: 1. EMPLICITI [package insert]. Princeton, NJ: Bristol-Myers Squibb Company. 2. REVLIMID [package insert]. Summit, NJ: Celgene Corp. 3. POMALYST [package insert]. Summit, NJ: Celgene Corp.
Please see below for Indications and Important Safety Information.
Bristol Myers Squibb is committed to helping appropriate patients initiate and maintain access to our medications during the treatment journey.
References: 1. EMPLICITI [package insert]. Princeton, NJ: Bristol-Myers Squibb Company. 2. REVLIMID [package insert]. Summit, NJ: Celgene Corp. 3. POMALYST [package insert]. Summit, NJ: Celgene Corp.
INDICATIONS
EMPLICITI® (elotuzumab) is indicated in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received one to three prior therapies.
EMPLICITI® (elotuzumab) is indicated in combination with POMALYST and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.
REVLIMID® (lenalidomide) is a thalidomide analogue indicated for the treatment of adult patients with multiple myeloma (MM) in combination with dexamethasone (dex).
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.
POMALYST® (pomalidomide) is a thalidomide analogue indicated, in combination with dexamethasone, for adult patients with MM who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy.
IMPORTANT SAFETY INFORMATION FOR REVLIMID, POMALYST & EMPLICITI
REVLIMID & POMALYST Boxed WARNINGS
WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, AND VENOUS and ARTERIAL THROMBOEMBOLISM
EMBRYO-FETAL TOXICITY: REVLIMID & POMALYST are thalidomide analogues and are contraindicated in pregnancy. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting treatment and use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping treatment. To avoid embryo-fetal exposure, REVLIMID and POMALYST are only available through their respective restricted distribution program Lenalidomide REMS and POMALYST REMS®.
Information about the Lenalidomide REMS program is available at www.lenalidomiderems.com or by calling 1-888-423-5436 and POMALYST REMS program is available at www.pomalystrems.com or by calling 1-888-423-5436.
HEMATOLOGIC TOXICITY: 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 & POMALYST have demonstrated a significantly increased risk of deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke in patients with MM. Thromboprophylaxis is recommended and the choice of regimen should be based on assessment of the patient’s underlying risk factors. 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.
CONTRAINDICATIONS
Pregnancy: See Boxed WARNINGS. REVLIMID & POMALYST can cause fetal harm when administered to a pregnant female and are contraindicated in females who are pregnant. If the patient becomes pregnant while taking REVLIMID or POMALYST, the patient should be apprised of the potential risk to the fetus.
Severe Hypersensitivity Reactions: REVLIMID & POMALYST are contraindicated in patients who have demonstrated severe hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis) to lenalidomide, pomalidomide, or any of the excipients.
REVLIMID, POMALYST & EMPLICITI WARNINGS AND PRECAUTIONS
Embryo-Fetal Toxicity & Females of Reproductive Potential: See Boxed WARNINGS. Females of reproductive potential must avoid pregnancy for at least 4 weeks before beginning REVLIMID or POMALYST.
REMS Program: See Boxed WARNINGS. Prescribers and pharmacies must be certified with the respective Lenalidomide or POMALYST REMS program by enrolling and complying with the REMS requirements; pharmacies must only dispense to patients who are authorized to receive REVLIMID or POMALYST. 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 & POMALYST can cause significant neutropenia and thrombocytopenia. Neutropenia, anemia, and thrombocytopenia were the most frequently reported Grade 3 or 4 adverse reactions in patients taking REVLIMID & POMALYST in clinical trials. Patients may require dose interruption and/or modification. For REVLIMID, monitor patients with neutropenia for signs of infection and advise patients to observe for bleeding or bruising, especially with use of concomitant medications that may increase risk of bleeding. Monitor complete blood counts (CBC) every 7 days for the first 2 cycles, on days 1 and 15 of cycle 3, and every 28 days thereafter. For POMALYST, monitor CBC weekly for the first 8 weeks and monthly thereafter.
Venous & Arterial Thromboembolism: See Boxed WARNINGS. Venous thromboembolic events (DVT and PE) and arterial thromboses (myocardial infarction [MI] and stroke [CVA]) are increased in patients treated with REVLIMID or POMALYST. Thromboprophylaxis is recommended and the regimen should be based on the patient’s underlying risks. 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). Erythropoietin-stimulating agents (ESAs) and estrogens may further increase the risk of thrombosis when used with REVLIMID 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. In patients taking REVLIMID, monitor for the development of SPM and take into account both the potential benefit of REVLIMID and risk of SPM when considering treatment. In patients receiving POMALYST as an investigational therapy outside of MM, cases of AML have been reported.
In the EMPLICITI ELOQUENT-2 trial (N=635), invasive second primary malignancies (SPM) were 9% (ERd) and 6% (Rd). The rate of hematologic malignancies was the same between ERd and Rd treatment arms (1.6%). Solid tumors were reported in 3.5% (ERd) and 2.2% (Rd). Skin cancer was reported in 4.4% (ERd) and 2.8% (Rd). In the ELOQUENT-3 trial (N=115), invasive SPMs were 0% (EPd) and 1.8% (Pd). Monitor patients for the development of SPMs.
Increased Mortality With Pembrolizumab: In clinical trials in patients with MM, the addition of pembrolizumab to a thalidomide analogue (REVLIMID or POMALYST) 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, have occurred in patients treated with REVLIMID + dexamethasone and POMALYST. Elevated levels of alanine aminotransferase and bilirubin have also been observed in patients treated with POMALYST. Monitor liver function tests monthly for POMALYST, and periodically for REVLIMID. Stop REVLIMID or POMALYST upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered.
In the ELOQUENT-2 trial (EMPLICITI + REVLIMID + dexamethasone vs REVLIMID + dexamethasone) (N=635), AST/ALT >3X the upper limit, total bilirubin >2X the upper limit, and alkaline phosphatase <2X the upper limit were 2.5% (EMPLICITI arm) vs 0.6% (control arm). Of 8 patients experiencing hepatotoxicity, 2 patients discontinued treatment while 6 patients had resolution and continued. Stop EMPLICITI upon ≥Grade 3 elevation of liver enzymes. Continuation of treatment may be considered after return to baseline values.
Infusion Reactions: Infusion reactions were reported in 10% of patients treated with EMPLICITI in the ELOQUENT-2 trial [EMPLICITI + REVLIMID + dexamethasone (ERd) vs REVLIMID + dexamethasone (Rd)] and 3.3% in the ELOQUENT-3 trial [EMPLICITI + POMALYST + dexamethasone (EPd) vs POMALYST + dexamethasone (Pd)]. In the ELOQUENT-2 trial, all infusion reactions were Grade 3 or lower, with Grade 3 infusion reactions occurring in 1% of patients. The most common symptoms included fever, chills, and hypertension. Bradycardia and hypotension also developed during infusions. In the trial, 5% of patients required interruption of the administration of EMPLICITI for a median of 25 minutes due to infusion reactions, and 1% of patients discontinued due to infusion reactions. Of the patients who experienced an infusion reaction, 70% (23/33) had them during the first dose. In the ELOQUENT-3 trial, the only infusion reaction symptom was chest discomfort (2%), which was Grade 1. All the patients who experienced an infusion reaction had them during the first treatment cycle.
Infections: In the ELOQUENT-2 trial (N=635), infections were reported in 81% of patients in the ERd arm and 74% in the Rd arm. Grade 3-4 infections were 28% (ERd) and 24% (Rd). Discontinuations due to infections were 3.5% (ERd) and 4.1% (Rd). Fatal infections were 2.5% (ERd) and 2.2% (Rd). Opportunistic infections were reported in 22% (ERd) and 13% (Rd). Fungal infections were 10% (ERd) and 5% (Rd). Herpes zoster was 14% (ERd) and 7% (Rd). In the ELOQUENT-3 trial (N=115), infections were reported in 65% of patients in both the EPd arm and the Pd arm. Grade 3-4 infections were reported in 13% (EPd) and 22% (Pd). Discontinuations due to infections were 7% (EPd) and 5% (Pd). Fatal infections were 5% (EPd) and 3.6% (Pd). Opportunistic infections were reported in 10% (EPd) and 9% (Pd). Herpes zoster was reported in 5% (EPd) and 1.8% (Pd). Monitor patients for development of infections and treat promptly.
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 with REVLIMID & POMALYST. DRESS may present with a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. These reactions can be fatal. Patients with a prior history of Grade 4 rash associated with thalidomide treatment should not receive REVLIMID. Consider REVLIMID & POMALYST interruption or discontinuation for Grade 2 or 3 skin rash. Permanently discontinue REVLIMID & POMALYST for Grade 4 rash, exfoliative or bullous rash, or for other severe cutaneous reactions such as SJS, TEN, or DRESS.
Tumor Lysis Syndrome (TLS): TLS may occur in patients treated with REVLIMID or POMALYST. Fatal instances of TLS have been reported during treatment with REVLIMID. Closely monitor patients at risk and take appropriate preventive approaches.
Hypersensitivity: Hypersensitivity including angioedema, anaphylaxis, and anaphylactic reactions to REVLIMID & POMALYST have been reported. Permanently discontinue REVLIMID & POMALYST for angioedema or anaphylaxis.
Dizziness & Confusional State: In patients taking POMALYST in clinical trials, 14% experienced dizziness (1% Grade 3 or 4) and 7% a confusional state (3% Grade 3 or 4). Instruct patients to avoid situations where dizziness or confusional state may be a problem and not to take other medications that may cause dizziness or confusional state without adequate medical advice.
Neuropathy: In patients taking POMALYST in clinical trials, 18% experienced neuropathy (2% Grade 3 in one trial) and 12% peripheral neuropathy.
Tumor Flare Reaction (TFR): Serious tumor flare reactions, 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.
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).
Interference with Determination of Complete Response: EMPLICITI is a humanized IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and possibly relapse from complete response in patients with IgG kappa myeloma protein.
ADVERSE REACTIONS
REVLIMID - Multiple Myeloma
POMALYST
EMPLICITI
DRUG INTERACTIONS
REVLIMID: 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.
POMALYST: Avoid concomitant use with strong inhibitors of CYP1A2. If concomitant use of a strong CYP1A2 inhibitor is unavoidable, reduce POMALYST dose to 2 mg.
USE IN SPECIFIC POPULATIONS
Please see full Prescribing Information for EMPLICITI, REVLIMID, and POMALYST, including Boxed WARNINGS for REVLIMID and POMALYST.
INDICATIONS
EMPLICITI® (elotuzumab) is indicated in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received one to three prior therapies.
EMPLICITI® (elotuzumab) is indicated in combination with POMALYST and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.
REVLIMID® (lenalidomide) is a thalidomide analogue indicated for the treatment of adult patients with multiple myeloma (MM) in combination with dexamethasone (dex).
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.
POMALYST® (pomalidomide) is a thalidomide analogue indicated, in combination with dexamethasone, for adult patients with MM who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy.
IMPORTANT SAFETY INFORMATION FOR REVLIMID, POMALYST & EMPLICITI
REVLIMID & POMALYST Boxed WARNINGS
WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, AND VENOUS and ARTERIAL THROMBOEMBOLISM
EMBRYO-FETAL TOXICITY: REVLIMID & POMALYST are thalidomide analogues and are contraindicated in pregnancy. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting treatment and use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping treatment. To avoid embryo-fetal exposure, REVLIMID and POMALYST are only available through their respective restricted distribution program Lenalidomide REMS and POMALYST REMS®.
Information about the Lenalidomide REMS program is available at www.lenalidomiderems.com or by calling 1-888-423-5436 and POMALYST REMS program is available at www.pomalystrems.com or by calling 1-888-423-5436.
HEMATOLOGIC TOXICITY: 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 & POMALYST have demonstrated a significantly increased risk of deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke in patients with MM. Thromboprophylaxis is recommended and the choice of regimen should be based on assessment of the patient’s underlying risk factors. 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.
CONTRAINDICATIONS
Pregnancy: See Boxed WARNINGS. REVLIMID & POMALYST can cause fetal harm when administered to a pregnant female and are contraindicated in females who are pregnant. If the patient becomes pregnant while taking REVLIMID or POMALYST, the patient should be apprised of the potential risk to the fetus.
Severe Hypersensitivity Reactions: REVLIMID & POMALYST are contraindicated in patients who have demonstrated severe hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis) to lenalidomide, pomalidomide, or any of the excipients.
REVLIMID, POMALYST & EMPLICITI WARNINGS AND PRECAUTIONS
Embryo-Fetal Toxicity & Females of Reproductive Potential: See Boxed WARNINGS. Females of reproductive potential must avoid pregnancy for at least 4 weeks before beginning REVLIMID or POMALYST.
REMS Program: See Boxed WARNINGS. Prescribers and pharmacies must be certified with the respective Lenalidomide or POMALYST REMS program by enrolling and complying with the REMS requirements; pharmacies must only dispense to patients who are authorized to receive REVLIMID or POMALYST. 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 & POMALYST can cause significant neutropenia and thrombocytopenia. Neutropenia, anemia, and thrombocytopenia were the most frequently reported Grade 3 or 4 adverse reactions in patients taking REVLIMID & POMALYST in clinical trials. Patients may require dose interruption and/or modification. For REVLIMID, monitor patients with neutropenia for signs of infection and advise patients to observe for bleeding or bruising, especially with use of concomitant medications that may increase risk of bleeding. Monitor complete blood counts (CBC) every 7 days for the first 2 cycles, on days 1 and 15 of cycle 3, and every 28 days thereafter. For POMALYST, monitor CBC weekly for the first 8 weeks and monthly thereafter.
Venous & Arterial Thromboembolism: See Boxed WARNINGS. Venous thromboembolic events (DVT and PE) and arterial thromboses (myocardial infarction [MI] and stroke [CVA]) are increased in patients treated with REVLIMID or POMALYST. Thromboprophylaxis is recommended and the regimen should be based on the patient’s underlying risks. 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). Erythropoietin-stimulating agents (ESAs) and estrogens may further increase the risk of thrombosis when used with REVLIMID 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. In patients taking REVLIMID, monitor for the development of SPM and take into account both the potential benefit of REVLIMID and risk of SPM when considering treatment. In patients receiving POMALYST as an investigational therapy outside of MM, cases of AML have been reported.
In the EMPLICITI ELOQUENT-2 trial (N=635), invasive second primary malignancies (SPM) were 9% (ERd) and 6% (Rd). The rate of hematologic malignancies was the same between ERd and Rd treatment arms (1.6%). Solid tumors were reported in 3.5% (ERd) and 2.2% (Rd). Skin cancer was reported in 4.4% (ERd) and 2.8% (Rd). In the ELOQUENT-3 trial (N=115), invasive SPMs were 0% (EPd) and 1.8% (Pd). Monitor patients for the development of SPMs.
Increased Mortality With Pembrolizumab: In clinical trials in patients with MM, the addition of pembrolizumab to a thalidomide analogue (REVLIMID or POMALYST) 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, have occurred in patients treated with REVLIMID + dexamethasone and POMALYST. Elevated levels of alanine aminotransferase and bilirubin have also been observed in patients treated with POMALYST. Monitor liver function tests monthly for POMALYST, and periodically for REVLIMID. Stop REVLIMID or POMALYST upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered.
In the ELOQUENT-2 trial (EMPLICITI + REVLIMID + dexamethasone vs REVLIMID + dexamethasone) (N=635), AST/ALT >3X the upper limit, total bilirubin >2X the upper limit, and alkaline phosphatase <2X the upper limit were 2.5% (EMPLICITI arm) vs 0.6% (control arm). Of 8 patients experiencing hepatotoxicity, 2 patients discontinued treatment while 6 patients had resolution and continued. Stop EMPLICITI upon ≥Grade 3 elevation of liver enzymes. Continuation of treatment may be considered after return to baseline values.
Infusion Reactions: Infusion reactions were reported in 10% of patients treated with EMPLICITI in the ELOQUENT-2 trial [EMPLICITI + REVLIMID + dexamethasone (ERd) vs REVLIMID + dexamethasone (Rd)] and 3.3% in the ELOQUENT-3 trial [EMPLICITI + POMALYST + dexamethasone (EPd) vs POMALYST + dexamethasone (Pd)]. In the ELOQUENT-2 trial, all infusion reactions were Grade 3 or lower, with Grade 3 infusion reactions occurring in 1% of patients. The most common symptoms included fever, chills, and hypertension. Bradycardia and hypotension also developed during infusions. In the trial, 5% of patients required interruption of the administration of EMPLICITI for a median of 25 minutes due to infusion reactions, and 1% of patients discontinued due to infusion reactions. Of the patients who experienced an infusion reaction, 70% (23/33) had them during the first dose. In the ELOQUENT-3 trial, the only infusion reaction symptom was chest discomfort (2%), which was Grade 1. All the patients who experienced an infusion reaction had them during the first treatment cycle.
Infections: In the ELOQUENT-2 trial (N=635), infections were reported in 81% of patients in the ERd arm and 74% in the Rd arm. Grade 3-4 infections were 28% (ERd) and 24% (Rd). Discontinuations due to infections were 3.5% (ERd) and 4.1% (Rd). Fatal infections were 2.5% (ERd) and 2.2% (Rd). Opportunistic infections were reported in 22% (ERd) and 13% (Rd). Fungal infections were 10% (ERd) and 5% (Rd). Herpes zoster was 14% (ERd) and 7% (Rd). In the ELOQUENT-3 trial (N=115), infections were reported in 65% of patients in both the EPd arm and the Pd arm. Grade 3-4 infections were reported in 13% (EPd) and 22% (Pd). Discontinuations due to infections were 7% (EPd) and 5% (Pd). Fatal infections were 5% (EPd) and 3.6% (Pd). Opportunistic infections were reported in 10% (EPd) and 9% (Pd). Herpes zoster was reported in 5% (EPd) and 1.8% (Pd). Monitor patients for development of infections and treat promptly.
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 with REVLIMID & POMALYST. DRESS may present with a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. These reactions can be fatal. Patients with a prior history of Grade 4 rash associated with thalidomide treatment should not receive REVLIMID. Consider REVLIMID & POMALYST interruption or discontinuation for Grade 2 or 3 skin rash. Permanently discontinue REVLIMID & POMALYST for Grade 4 rash, exfoliative or bullous rash, or for other severe cutaneous reactions such as SJS, TEN, or DRESS.
Tumor Lysis Syndrome (TLS): TLS may occur in patients treated with REVLIMID or POMALYST. Fatal instances of TLS have been reported during treatment with REVLIMID. Closely monitor patients at risk and take appropriate preventive approaches.
Hypersensitivity: Hypersensitivity including angioedema, anaphylaxis, and anaphylactic reactions to REVLIMID & POMALYST have been reported. Permanently discontinue REVLIMID & POMALYST for angioedema or anaphylaxis.
Dizziness & Confusional State: In patients taking POMALYST in clinical trials, 14% experienced dizziness (1% Grade 3 or 4) and 7% a confusional state (3% Grade 3 or 4). Instruct patients to avoid situations where dizziness or confusional state may be a problem and not to take other medications that may cause dizziness or confusional state without adequate medical advice.
Neuropathy: In patients taking POMALYST in clinical trials, 18% experienced neuropathy (2% Grade 3 in one trial) and 12% peripheral neuropathy.
Tumor Flare Reaction (TFR): Serious tumor flare reactions, 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.
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).
Interference with Determination of Complete Response: EMPLICITI is a humanized IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and possibly relapse from complete response in patients with IgG kappa myeloma protein.
ADVERSE REACTIONS
REVLIMID - Multiple Myeloma
POMALYST
EMPLICITI
DRUG INTERACTIONS
REVLIMID: 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.
POMALYST: Avoid concomitant use with strong inhibitors of CYP1A2. If concomitant use of a strong CYP1A2 inhibitor is unavoidable, reduce POMALYST dose to 2 mg.
USE IN SPECIFIC POPULATIONS
Please see full Prescribing Information for EMPLICITI, REVLIMID, and POMALYST, including Boxed WARNINGS for REVLIMID and POMALYST.