Generic Name: Elotuzumab
Class: Antineoplastic Agents
Elotuzumab is an antineoplastic agent.
Uses for Empliciti
Elotuzumab has the following uses:
Elotuzumab is a SLAMF7-directed immunostimulatory antibody indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior therapies.1
Empliciti Dosage and Administration
Elotuzumab is available in the following dosage form(s) and strength(s):
For Injection: 300 mg or 400 mg lyophilized powder in a single-dose vial for reconstitution.1
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
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. 1
Premedicate with dexamethasone, diphenhydramine, ranitidine and acetaminophen. 1
Cautions for Empliciti
Elotuzumab can cause infusion reactions. Infusion reactions were reported in approximately 10% of patients treated with elotuzumab with lenalidomide and dexamethasone in the randomized trial in multiple myeloma. All reports of infusion reaction were Grade 3 or lower. Grade 3 infusion reactions occurred in 1% of patients. The most common symptoms of an infusion reaction included fever, chills, and hypertension. Bradycardia and hypotension also developed during infusions.1
In the trial, 5% of patients required interruption of the administration of elotuzumab 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.1
Administer premedication consisting of dexamethasone, antihistamines (H1 and H2 blockers) and acetaminophen prior to elotuzumab infusion.1
Interrupt elotuzumab infusion for Grade 2 or higher infusion reactions and institute appropriate medical management.1
In a clinical trial of patients with multiple myeloma (N=635), infections were reported in 81.4% of patients in the elotuzumab combined with lenalidomide and dexamethasone (E-Ld) arm and 74.4% in lenalidomide and dexamethasone (Ld). Grade 3 to 4 infections were noted in 28% and 24.3% of E-Ld- and Ld-treated patients, respectively. Discontinuations due to infections occurred in 3.5% of E-Ld-treated and 4.1% of Ld-treated patients. Fatal infections were reported in 2.5% and 2.2% of E-Ld- and Ld-treated patients.1
Opportunistic infections were reported in 22% of patients in the E-Ld arm and 12.9% of patients in the Ld arm. Fungal infections occurred in 9.7% of patients in the E-Ld arm and 5.4% of patients in the Ld arm. Herpes zoster was reported in 13.5% of patients treated with E-Ld and 6.9% of patients treated with Ld. Monitor patients for development of infections and treat promptly.1
Second Primary Malignancies
In a clinical trial of patients with multiple myeloma (N=635), invasive second primary malignancies (SPM) have been observed in 9.1% of patients treated with E-Ld and 5.7% of patients treated with Ld. The rate of hematologic malignancies were the same between E-Ld and Ld treatment arms (1.6%). Solid tumors were reported in 3.5% and 2.2% of E-Ld- and Ld-treated patients, respectively. Skin cancer was reported in 4.4% and 2.8% of patients treated with E-Ld and Ld, respectively. Monitor patients for the development of second primary malignancies.1
Elevations in liver enzymes (aspartate transaminase/alanine transaminase [AST/ALT] greater than 3 times the upper limit, total bilirubin greater than 2 times the upper limit, and alkaline phosphatase less than 2 times the upper limit) consistent with hepatotoxicity were reported in 2.5% and 0.6% of E-Ld- and Ld-treated patients in a clinical trial of patients with multiple myeloma (N=635). Two patients experiencing hepatotoxicity were not able to continue treatment; however, 6 out of 8 patients had resolution and were able to continue treatment. Monitor liver enzymes periodically. Stop elotuzumab upon Grade 3 or higher elevation of liver enzymes. After return to baseline values, continuation of treatment may be considered.1
Interference With Determination Of Complete Response
Elotuzumab is a humanized IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPEP) and immunofixation (IFE) 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.1
There are no studies with elotuzumab with pregnant women to inform any drug associated risks. Animal reproduction studies have not been conducted with elotuzumab.1
Elotuzumab is administered in combination with lenalidomide and dexamethasone. Lenalidomide can cause embryo-fetal harm and is contraindicated for use in pregnancy. Refer to the lenalidomide and dexamethasone prescribing information for additional information. Lenalidomide is only available through a REMS program.1
The background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.1
There is no information on the presence of elotuzumab in human milk, the effect on the breast-fed infant, or the effect on milk production. Because of the potential for serious adverse reactions in breast-fed infants from elotuzumab administered with lenalidomide/dexamethasone, breastfeeding is not recommended. Refer to the lenalidomide and dexamethasone prescribing information for additional information.1
Females And Males Of Reproductive Potential
Refer to the lenalidomide labeling for pregnancy testing requirements prior to initiating treatment in females of reproductive potential.1
When elotuzumab is used with lenalidomide, there is a risk of fetal harm, including severe life-threatening human birth defects associated with lenalidomide, and the need to follow requirements regarding pregnancy avoidance, including testing.1
Refer to the lenalidomide labeling for contraception requirements prior to initiating treatment in females of reproductive potential and males.1
Lenalidomide is present in the blood and semen of patients receiving the drug. Refer to the lenalidomide full prescribing information for requirements regarding contraception and the prohibitions against blood and/or sperm donation due to presence and transmission in blood and/or semen and for additional information.1
Safety and effectiveness have not been established in pediatric patients.1
Of the 646 patients across treatment groups in the randomized trial in multiple myeloma, 57% were 65 years of age or older; the number of patients 65 years or older was similar between treatment groups. No overall differences in efficacy or safety were observed between patients 65 years or older and younger patients (less than 65 years of age).1
Common Adverse Effects
Most common adverse reactions (20% or higher) are fatigue, diarrhea, pyrexia, constipation, cough, peripheral neuropathy, nasopharyngitis, upper respiratory tract infection, decreased appetite, pneumonia. 1
It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:
Please see product labeling for drug interaction information.
Mechanism Of Action
Elotuzumab is a humanized IgG1 monoclonal antibody that specifically targets the SLAMF7 (Signaling Lymphocytic Activation Molecule Family member 7) protein. SLAMF7 is expressed on myeloma cells independent of cytogenetic abnormalities. SLAMF7 is also expressed on Natural Killer cells, plasma cells, and at lower levels on specific immune cell subsets of differentiated cells within the hematopoietic lineage.1
Elotuzumab directly activates Natural Killer cells through both the SLAMF7 pathway and Fc receptors. Elotuzumab also targets SLAMF7 on myeloma cells and facilitates the interaction with Natural Killer cells to mediate the killing of myeloma cells through antibody-dependent cellular cytotoxicity (ADCC). In preclinical models, the combination of elotuzumab and lenalidomide resulted in enhanced activation of Natural Killer cells that was greater than the effects of either agent alone and increased anti-tumor activity in vitro and in vivo .1
Advice to Patients
Advise the patient to read the FDA-approved patient labeling .1
Elotuzumab may cause infusion reactions. Advise patients to contact their healthcare provider if they experience signs and symptoms of infusion reactions, including fever, chills, rash, or breathing problems within 24 hours of infusion.1
Advise patients that they will be required to take the following oral medications prior to elotuzumab dosing to reduce the risk of infusion reaction: Dexamethasone orally as prescribed; H1 blocker: diphenhydramine or equivalent (if oral); H2 blocker: ranitidine or equivalent (if oral); Acetaminophen (650-1000 mg orally).1
Advise patients that lenalidomide has the potential to cause fetal harm and has specific requirements regarding contraception, pregnancy testing, blood and sperm donation, and transmission in sperm. Lenalidomide is only available through a REMS program.1
Inform patients of the risk of developing infections during treatment with elotuzumab, and to report any symptoms of infection.1
Second Primary Malignancies
Inform patients of the risk of developing SPM during treatment with elotuzumab.1
Inform patients of the risk of hepatotoxicity during treatment with elotuzumab and to report any signs and symptoms associated with this event to their healthcare provider for evaluation.1
AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Injection, Powder, Lyophilized, For Solution
E.R. Squibb & Sons L.L.C.
E.R. Squibb & Sons L.L.C.
AHFS Drug Information. © Copyright 2016, Selected Revisions September 12, 2016. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. E.R. Squibb & Sons, L.L.C.. EMPLICITI (elotuzumab) INTRAVENOUS prescribing information.