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Indications & Usage

INDICATIONS AND USAGE

EMPLICITI is a SLAMF7-directed immunostimulatory antibody indicated in

•        combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received one to three prior therapies.

•        combination with pomalidomide 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.

 

 

Please see full Prescribing Information for EMPLICITI and full Prescribing Information for POMALYST, including Boxed WARNINGS.

Dosage & Administration

DOSAGE AND ADMINISTRATION

•        With lenalidomide and dexamethasone: 10 mg/kg administered intravenously every week for the first two cycles and every 2 weeks thereafter until disease progression or unacceptable toxicity.

•        With pomalidomide and dexamethasone: 10 mg/kg administered intravenously every week for the first two cycles and 20 mg/kg every 4 weeks thereafter until disease progression or unacceptable toxicity.

•        Premedicate with dexamethasone, diphenhydramine, H2 blocker and acetaminophen.

 

DOSAGE FORMS AND STRENGTHS

For Injection:  300 mg or 400 mg lyophilized powder in a single-dose vial for reconstitution.

 

 

Please see full Prescribing Information for EMPLICITI and full Prescribing Information for POMALYST, including Boxed WARNINGS.

Contraindications

CONTRAINDICATIONS

None.

 

 

Please see full Prescribing Information for EMPLICITI and full Prescribing Information for POMALYST, including Boxed WARNINGS.

Warnings & Precautions

WARNINGS AND PRECAUTIONS

•        Infusion reactions: Premedication is required. Interrupt EMPLICITI (elotuzumab) for Grade 2 or higher and permanently discontinue for severe infusion reaction.

•        Infections: Monitor for fever and other signs of infection and treat promptly.

•        Second Primary Malignancies (SPM): Higher incidences of SPM were observed in a controlled clinical trial of patients with multiple myeloma receiving EMPLICITI.

•        Hepatotoxicity: Monitor liver function and stop EMPLICITI if hepatotoxicity is suspected.

•        Interference with determination of complete response: EMPLICITI can interfere with assays used to monitor M-protein. This interference can impact the determination of complete response.

 

 

Please see full Prescribing Information for EMPLICITI and full Prescribing Information for POMALYST, including Boxed WARNINGS.

Adverse Reactions

ADVERSE REACTIONS

Most common adverse reactions (20% or higher)

•        with lenalidomide and dexamethasone are fatigue, diarrhea, pyrexia, constipation, cough, peripheral neuropathy, nasopharyngitis, upper respiratory tract infection, decreased appetite, pneumonia.

•        with pomalidomide and dexamethasone are constipation and hyperglycemia.

To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

 

Please see full Prescribing Information for EMPLICITI and full Prescribing Information for POMALYST, including Boxed WARNINGS.

EMPLICITI® and its associated logo are registered trademarks of Bristol-Myers Squibb Company.

POMALYST®, its associated logo, and POMALYST REMS® are registered trademarks of Celgene Corporation, a Bristol Myers Squibb company.

© 2022 Bristol-Myers Squibb Company.          689-US-2200046      12/22   

 

Please see full Prescribing Information for EMPLICITI and full Prescribing Information for POMALYST, including Boxed WARNINGS.

INDICATIONS 

 

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.

 

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 POMALYST & EMPLICITI

 

POMALYST Boxed WARNINGS

WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISM

EMBRYO-FETAL TOXICITY: POMALYST is a thalidomide analogue and is 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, POMALYST is only available through its restricted distribution program, POMALYST REMS® .

Information about the POMALYST REMS programs is available at www.celgeneriskmanagement.com or by calling 1-888-423-5436.

VENOUS AND ARTERIAL THROMBOEMBOLISM: POMALYST has 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. POMALYST can cause fetal harm when administered to a pregnant female and is contraindicated in females who are pregnant. If the patient becomes pregnant while taking POMALYST, the patient should be apprised of the potential risk to the fetus.


Severe Hypersensitivity Reactions: POMALYST is contraindicated in patients who have demonstrated severe hypersensitivity (e.g., angioedema, anaphylaxis) to pomalidomide, or any of the excipients. 

 

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 POMALYST.

  • Males: POMALYST 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 POMALYST even if they have undergone a successful vasectomy. This protective measure must be followed for up to 4 weeks after discontinuing POMALYST. Males must not donate sperm while taking POMALYST.
  • Blood Donation: Patients must not donate blood during treatment with POMALYST and for 4 weeks following discontinuation of the drug, as the blood might be given to a pregnant female patient whose fetus must not be exposed to POMALYST.

 

REMS Program: See Boxed WARNINGS. 
          -Prescribers and pharmacies must be certified with the POMALYST REMS program by enrolling and complying with the REMS requirements; pharmacies must only dispense to patients who are authorized to receive 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.
          -Further information about the POMALYST REMS program is available at www.CelgeneRiskManagement.com or by telephone at 1-888-423-5436. 

 

Hematologic Toxicity: POMALYST can cause significant neutropenia (46%) and thrombocytopenia. Neutropenia, anemia, and thrombocytopenia were the most frequently reported Grade 3 or 4 adverse reactions in patients taking POMALYST in clinical trials. Patients may require dose interruption and/or modification. 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 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).

 

Second Primary Malignancies (SPM): In patients receiving POMALYST as an investigational therapy outside of MM, cases of AML have been reported.
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 (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 POMALYST. Elevated levels of alanine aminotransferase and bilirubin have also been observed in patients treated with POMALYST. Monitor liver function tests monthly for POMALYST. Stop POMALYST upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered.  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 3.3% in the ELOQUENT-3 trial [EMPLICITI + POMALYST + dexamethasone (EPd) vs POMALYST + dexamethasone (Pd)]. 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. The most common symptoms included fever, chills, and hypertension. Bradycardia and hypotension also developed during infusions.
  • If a Grade 2 or higher infusion reaction occurs, interrupt the EMPLICITI infusion and institute appropriate medical and supportive measures. If the infusion reaction recurs, stop the EMPLICITI infusion and do not restart it on that day. Severe infusion reactions may require permanent discontinuation of EMPLICITI therapy and emergency treatment.
  • Premedicate with dexamethasone, H1 blocker, H2 blocker, and acetaminophen prior to EMPLICITI infusion.

Infections

  • 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 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. Consider POMALYST interruption or discontinuation for Grade 2 or 3 skin rash. Permanently discontinue 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 POMALYST. Patients at risk are those with high tumor burden prior to treatment. Closely monitor patients at risk and take appropriate preventive approaches.

Hypersensitivity: Hypersensitivity including angioedema, anaphylaxis, and anaphylactic reactions to POMALYST have been reported. Permanently discontinue 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.


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

POMALYST

  • The most common adverse reactions for POMALYST (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain, and pyrexia.
  • In the phase III trial, nearly all patients treated with POMALYST + low-dose dex experienced at least one adverse reaction (99%). Adverse reactions (≥15% in the POMALYST + low-dose dex arm and ≥2% higher than control) included neutropenia (51%), fatigue and asthenia (47%), upper respiratory tract infection (31%), thrombocytopenia (30%), pyrexia (27%), dyspnea (25%), diarrhea (22%), constipation (22%), back pain (20%), cough (20%), pneumonia (19%), bone pain (18%), edema peripheral (17%), peripheral neuropathy (17%), muscle spasms (15%), and nausea (15%). Grade 3 or 4 adverse reactions (≥15% in the POMALYST + low-dose dex arm and ≥1% higher than control) included neutropenia (48%), thrombocytopenia (22%), and pneumonia (16%).

EMPLICITI

  • ELOQUENT-3 trial: Serious adverse reactions were 70% (EPd) and 60% (Pd). The most frequent serious adverse reactions in the EPd arm compared to the Pd arm were: pneumonia (13%, 11%) and respiratory tract infection (7%, 3.6%). The most common adverse reactions in EPd arm (≥20% EPd) and Pd, respectively, were constipation (22%, 11%) and hyperglycemia (20%, 15%).

 

DRUG INTERACTIONS

  • 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

  • Pregnancy: See Boxed WARNINGS for POMALYST. 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 POMALYST pregnancy exposure registry that monitors pregnancy outcomes in females exposed to POMALYST during pregnancy as well as female partners of male patients who are exposed to POMALYST. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure of the drug to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation, a Bristol Myers Squibb company, at 1-888-423-5436.
  • Pregnancy and EMPLICITI Use: There are no available data on EMPLICITI use in pregnant women to inform a drug-associated risk of major defects and miscarriage.
  • Lactation: There is no information regarding the presence of pomalidomide or elotuzumab in human milk, the effects of POMALYST or EMPLICITI on the breastfed child, or the effects of POMALYST, REVLIMID or EMPLICITI on milk production. Pomalidomide was excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for adverse reactions in a breastfed child from POMALYST or REVLIMID, advise women not to breastfeed during treatment.
  • Pediatric Use: Safety and effectiveness of POMALYST or in combination with EMPLICITI have not been established in pediatric patients.
  • Geriatric Use: No dose adjustment is required for POMALYST based on age. Patients >65 years of age were more likely than patients ≤65 years of age to experience pneumonia.
  • Renal Impairment: For POMALYST in patients with severe renal impairment requiring dialysis, reduce the recommended dosage to 3 mg orally daily. Take dose of POMALYST following hemodialysis on hemodialysis days.
  • Hepatic Impairment: In patients with mild to moderate hepatic impairment, reduce POMALYST dosage to 3 mg orally daily and to 2 mg orally daily in patients with severe hepatic impairment.
  • Smoking Tobacco: Advise patients that smoking may reduce the efficacy of POMALYST. Cigarette smoking reduces pomalidomide AUC due to CYP1A2 induction.

 

Please see full Prescribing Information for POMALYST and EMPLICITI, including Boxed WARNINGS, for POMALYST.