Elotuzumab Intravenous
Elotuzumab, a recombinant humanized monoclonal antibody that is an antagonist of signaling lymphocytic activation molecule (SLAM) family member 7 (SLAMF7), is an antineoplastic agent;[1][6] the drug also is referred to as an anti-CS1 (anti-CD2 subset 1) monoclonal antibody.[2][10][11][12][16]
Brand Name: Empliciti intravenous
Class: Antineoplastic Agents (10:00)
Table of Contents
Uses
Multiple Myeloma
Elotuzumab is used in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma in patients who have received 1-3 prior therapies.[1][2][14] Elotuzumab has been designated an orphan drug by FDA for the treatment of this cancer.[3] In patients with relapsed or refractory multiple myeloma, combined therapy with elotuzumab, lenalidomide, and dexamethasone has been shown to prolong progression-free survival and increase response rate compared with lenalidomide and dexamethasone alone.[1][2]
The current indication for elotuzumab is based principally on the results of a randomized, open-label, multicenter, phase 3 study (ELOQUENT-2) in adults with relapsed or refractory multiple myeloma who had received 1-3 prior therapies.[1][2] Patients were enrolled if they had documented disease progression following their most recent therapy.[1][2] In this study, 646 adults were randomized in a 1:1 ratio to receive either elotuzumab (10 mg/kg IV on days 1, 8, 15, and 22 during cycles 1 and 2, followed by 10 mg/kg on days 1 and 15 during cycle 3 and onward) in combination with lenalidomide (25 mg orally on days 1-21) and dexamethasone (28 mg of dexamethasone orally plus 8 mg of dexamethasone phosphate IV on days 1, 8, 15, and 22 during cycles 1 and 2, followed by 28 mg orally plus 8 mg IV on days 1 and 15 and 40 mg orally on days 8 and 22 during cycle 3 and onward) or lenalidomide (25 mg orally on days 1-21) in combination with dexamethasone (40 mg orally on days 1, 8, 15, and 22).[1][2] Therapy was administered in 4-week cycles until disease progression or unacceptable toxicity occurred.[1][2] Prior to each elotuzumab infusion, patients also received acetaminophen, a histamine H2-receptor antagonist, and a histamine H1-receptor antagonist as prophylaxis for infusion-related reactions.[2] All enrolled patients were required to receive thromboprophylaxis.[2] The primary end points of this study were progression-free survival and overall response rate, which was assessed by a blinded independent review committee according to the European Group for Blood and Marrow Transplantation (EBMT) response criteria.[1][2]
The median age of patients enrolled in the ELOQUENT-2 study was 66 years (range: 37-91 years); 84% of patients were white, 91% had an ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1, 43% had stage I disease according to the International Staging System (ISS), 32% had stage II disease, and 21% had stage III disease.[1][2] Patients enrolled in the study had received a median of 2 prior therapies; 70% of patients had previously received bortezomib, 65% had received melphalan, 48% had received thalidomide, 6% had received lenalidomide, and 55% had undergone stem cell transplantation.[1][2] Approximately 65 or 35% of patients had relapsed or refractory disease, respectively.[1] High-risk cytogenetic features, t(4;14) translocation or 17p deletion, were present in 9 or 32% of patients, respectively.[1][2]
At a median follow-up of 24.5 months, median progression-free survival was prolonged in patients who received elotuzumab in combination with lenalidomide and dexamethasone compared with those who received lenalidomide and dexamethasone alone (19 versus 15 months; hazard ratio: 0.7).[1][2] The rates of 1- and 2-year progression-free survival were higher in patients receiving elotuzumab in combination with lenalidomide and dexamethasone (68 and 41%, respectively) compared with those receiving lenalidomide and dexamethasone alone (57 and 27%, respectively).[1][2] In addition, patients receiving elotuzumab in combination with lenalidomide and dexamethasone had higher overall response rates (79 versus 66%) and more-durable responses (21 versus 17 months) compared with those receiving lenalidomide and dexamethasone alone.[1][2] Median overall survival had not been reached at the time of the analysis.[2] Results of a subgroup analysis (based on age, disease stage, baseline β2-microglobulin concentration, response to most recent line of therapy, prior exposure to bortezomib or an immunomodulatory agent, prior stem cell transplantation, presence of high-risk cytogenetic features, baseline creatinine clearance) suggested that the drug's effect on progression-free survival was consistent across all subgroups.[2]
Dosage And Administration
General
Clinicians should consult the respective manufacturers' labelings for information on the dosage and method of administration of other antineoplastic agents used in combination regimens.[1]
To minimize the risk of infusion-related events associated with elotuzumab, the manufacturer recommends premedication with oral acetaminophen 650 mg to 1 g, an oral or IV histamine H2-receptor antagonist (e.g., ranitidine 50 mg IV or 150 mg orally or equivalent), an oral or IV histamine H1-receptor antagonist (e.g., diphenhydramine hydrochloride 25-50 mg or equivalent), and IV dexamethasone phosphate 8 mg administered 45-90 minutes prior to each elotuzumab infusion.[1]
Restricted Distribution Program
Elotuzumab can only be obtained through select specialty distributors.[4] Clinicians may consult the Empliciti® website for specific availability information (https://www.emplicitihcp.com/ordering).[4]
Administration
Elotuzumab is administered by IV infusion using a sterile, nonpyrogenic, low-protein-binding, 0.2- to 1.2-mcm inline filter.[1] Solutions of the drug should be administered via an infusion pump.[1] Other drugs should not be administered simultaneously through the same IV line with elotuzumab infusion.[1]
Prior to administration, commercially available elotuzumab lyophilized powder for injection must be reconstituted and diluted using proper aseptic technique.[1]
Unreconstituted elotuzumab lyophilized powder for injection should be stored in unopened vials at 2-8°C, and should not be frozen or shaken.[1] Unopened vials should be retained in the original package for protection from light.[1]
Reconstitution
The manufacturer recommends use of a 15- to 18-gauge needle for preparation.[1] The lyophilized powder is reconstituted by adding 13 mL of sterile water for injection to a vial labeled as containing 300 mg of elotuzumab or by adding 17 mL of sterile water for injection to a vial labeled as containing 400 mg of elotuzumab to provide a solution containing 25 mg/mL.[1] The 300- and 400-mg vials are formulated to provide a slight overfill when reconstituted as directed.[1] Slight back pressure may occur when injecting the diluent into the vial.[1] The vials should be held upright and swirled to facilitate dissolution of the lyophilized powder, which should dissolve in less than 10 minutes, and then inverted a few times to facilitate dissolution of lyophilized powder that may be present on top of the vial or on the stopper.[1] The vials should not be shaken or vigorously agitated.[1] The contents of the reconstituted vials should not be removed until all of the solids have completely dissolved and the solution has been allowed to stand for about 5-10 minutes.[1] The reconstituted solution should be inspected visually for particulate matter and discoloration prior to dilution and should not be used if particles are present or if the solution appears discolored.[1] The resulting solution should be colorless to slightly yellow and clear to slightly opalescent.[1]
Commercially available elotuzumab lyophilized powder for injection contains no preservatives and is intended for single use; any partially used vials should be discarded.[1]
Dilution
The appropriate dose (10 mg/kg) of reconstituted elotuzumab solution (containing 25 mg/mL) should be withdrawn and added to a polyvinylchloride (PVC) or non-PVC (polyolefin) infusion bag containing 230 mL of 0.9% sodium chloride or 5% dextrose injection.[1] The volume of 0.9% sodium chloride or 5% dextrose injection may be adjusted to avoid exceeding 5 mL of fluid per kg of patient weight.[1]
If immediate administration is not possible, diluted solutions of the drug should be protected from light and stored at 2-8°C for up to 24 hours; however, diluted solutions of the drug may be stored at 20-25°C under room light for up to 8 hours during the 24-hour period.[1] Infusion of diluted elotuzumab solutions should be completed within 24 hours of reconstitution.[1]
Elotuzumab should not be admixed with any other drug.[1]
Rate of Administration
The initial elotuzumab dose (day 1 of cycle 1) should be infused IV at an initial rate of 0.5 mL/minute; if infusion-related reactions do not occur, the infusion rate may be doubled every 30 minutes up to a maximum rate of 2 mL/minute.[1] The second dose of elotuzumab (day 8 of cycle 1) should be infused at an initial rate of 1 mL/minute; if infusion-related reactions do not occur within 30 minutes of initiating the infusion, the infusion rate may be increased to 2 mL/minute.[1] Subsequent doses of elotuzumab should be infused at a rate of 2 mL/minute.[1] The maximum infusion rate should not exceed 2 mL/minute; however, in patients who have received 4 cycles of elotuzumab, the infusion rate may be increased to a maximum infusion rate of 5 mL/minute.[1]
If infusion-related reactions occur, elotuzumab therapy should be interrupted and the infusion rate should be reduced depending on the severity of the reaction, and appropriate symptomatic and supportive therapy should be provided as clinically indicated.[1] If the infusion-related reaction is grade 2 or greater in severity, therapy with elotuzumab should be interrupted and appropriate medical treatment should be provided; once the reaction has resolved to grade 1 or less, the infusion may be resumed at a rate of 0.5 mL/minute and may be increased as tolerated in increments of 0.5 mL/minute every 30 minutes to the rate at which the infusion-related reaction occurred.[1] If infusion-related reactions do not recur, the infusion rate may be increased in increments and intervals appropriate for the treatment cycle dose (as described in the previous paragraph).[1] (See Infusion-related Effects under Cautions: Warnings/Precautions.) If infusion-related reactions recur, elotuzumab therapy should be interrupted and not restarted on that same day.[1] If severe infusion-related reactions occur, permanent discontinuance of elotuzumab therapy may be necessary and emergency treatment should be provided.[1]
Dosage
Multiple Myeloma
For use in combination with lenalidomide and dexamethasone in the treatment of multiple myeloma in adults who have received 1-3 prior therapies, the recommended dosage of elotuzumab is 10 mg/kg administered IV once weekly (days 1, 8, 15, and 22) with lenalidomide 25 mg administered orally once daily on days 1-21 and dexamethasone 28 mg administered orally on days 1, 8, 15, and 22 of each 28-day cycle during cycles 1 and 2.[1] During cycle 3 and onward, the recommended dosage of elotuzumab is 10 mg/kg administered IV every 2 weeks (days 1 and 15) with lenalidomide 25 mg administered orally once daily on days 1-21 and dexamethasone 28 mg administered orally on days 1 and 15 and 40 mg administered orally on days 8 and 22 of each 28-day cycle.[1] The oral dexamethasone dose (28 versus 40 mg) varies according to whether elotuzumab is administered that day.[1] On days that elotuzumab is not administered but dexamethasone is scheduled, a 40-mg oral dexamethasone dose is administered.[1] On days that elotuzumab is administered, dexamethasone 28 mg is administered orally 3-24 hours prior to administration of elotuzumab, with an additional 8-mg IV dose of dexamethasone phosphate given as premedication.[1] To minimize the risk of infusion-related events associated with elotuzumab, appropriate premedications (including IV dexamethasone phosphate) should be administered 45-90 minutes prior to administration of elotuzumab.[1] (See Dosage and Administration: General.)
Therapy should be continued until disease progression or unacceptable toxicity occurs.[1]
Dosage Modification
If administration of one drug in the combination regimen is delayed, interrupted, or discontinued, therapy with the other drugs may be continued; however, since dexamethasone also is used to reduce the risk of infusion-related events associated with elotuzumab, clinical judgment should be used in deciding whether elotuzumab should be continued without dexamethasone.[1] Clinicians should consult the respective manufacturers' labelings for information on recommended dosage modifications for lenalidomide and dexamethasone.[1]
Special Populations
The manufacturer makes no special population dosage recommendations at this time.[1] (See Specific Populations under Cautions: Warnings/Precautions.)
Cautions
Contraindications
The manufacturer states there are no known contraindications to the use of elotuzumab.[1]
Warnings/Precautions
Combination Therapy
When elotuzumab is used in combination with lenalidomide and dexamethasone, the usual cautions, precautions, and contraindications associated with lenalidomide and dexamethasone must be considered in addition to those associated with elotuzumab.[1] For further information regarding warnings and precautions associated with lenalidomide and dexamethasone, see Cautions in Lenalidomide 10:00 and also in the Corticosteroids General Statement 68:04.
Infusion-related Effects
Infusion-related reactions have been reported in patients receiving elotuzumab in combination with lenalidomide and dexamethasone.[1][2] Infusion-related reactions generally occurred more frequently during the first infusion.[1] In the ELOQUENT-2 study, infusion reactions were reported in approximately 10% (grade 3 in 1%) of patients receiving elotuzumab in combination with lenalidomide and dexamethasone; the most common infusion-related reactions were pyrexia, chills, and hypertension.[1] Infusion-related reactions also have included bradycardia and hypotension.[1] Infusion-related reactions requiring temporary interruption or discontinuance of elotuzumab therapy occurred in 5 or 1%, respectively, of patients; the median time for temporarily interrupting elotuzumab therapy was 25 minutes.[1]
To minimize the risk of infusion-related reactions, patients receiving elotuzumab should be premedicated with acetaminophen, a histamine H2-receptor antagonist, histamine H1-receptor antagonist, and dexamethasone prior to administration of the drug.[1] (See Dosage and Administration: General.)
If infusion-related reactions occur, elotuzumab therapy should be interrupted and the infusion rate should be reduced depending on the severity of the reaction, and appropriate symptomatic and supportive therapy should be provided as clinically indicated.[1] (See Rate of Administration under Dosage and Administration: Administration.) In patients who experience infusion-related reactions, vital signs should be monitored every 30 minutes for 2 hours following the end of the infusion.[1] If severe infusion-related reactions occur, permanent discontinuance of elotuzumab therapy may be necessary and emergency treatment should be provided.[1]
Infectious Complications
Infections, sometimes fatal or requiring discontinuance of therapy, have been reported in patients receiving elotuzumab in combination with lenalidomide and dexamethasone.[1][2] In the ELOQUENT-2 study, infection was reported in 81.4% (grade 3 or 4 in 28%) of patients receiving elotuzumab in combination with lenalidomide and dexamethasone compared with 74.4% (grade 3 or 4 in 24.3%) of those receiving lenalidomide and dexamethasone alone.[1] Opportunistic infections, fungal infections, and herpes zoster occurred in 22, 9.7, and 13.5%, respectively, of elotuzumab-treated patients compared with 12.9, 5.4, and 6.9%, respectively, of patients receiving lenalidomide and dexamethasone alone.[1] Fatal infections occurred in 2.5% of elotuzumab-treated patients compared with 2.2% of patients receiving lenalidomide and dexamethasone alone.[1]
Patients should be monitored for signs and symptoms of infection.[1] If an infection develops, therapy should be initiated promptly.[1]
Development of Second Primary Malignancy
Second primary malignancies have been reported in patients receiving elotuzumab in combination with lenalidomide and dexamethasone.[1] In the ELOQUENT-2 study, invasive second primary malignancies were reported more frequently in patients receiving elotuzumab in combination with lenalidomide and dexamethasone compared with those receiving lenalidomide and dexamethasone alone (9.1 versus 5.7%).[1] In this study, solid tumors and skin cancer occurred in 3.5 and 4.4%, respectively, of elotuzumab-treated patients compared with 2.2 and 2.8%, respectively, of those receiving lenalidomide and dexamethasone alone; however, the incidence of hematologic malignancies was similar between elotuzumab-treated patients and those receiving lenalidomide and dexamethasone alone (1.6%).[1]
Patients should be monitored for development of second primary malignancies.[1]
Hepatic Effects
Liver function test abnormalities have been reported in patients receiving elotuzumab in combination with lenalidomide and dexamethasone.[1] In the ELOQUENT-2 study, concurrent elevations in ALT or AST (exceeding 3 times the upper limit of normal [ULN]) and total bilirubin concentrations (exceeding 2 times the ULN) with normal alkaline phosphatase concentrations (less than 2 times the ULN) occurred in 2.5% of patients receiving elotuzumab in combination with lenalidomide and dexamethasone and in 0.6% of those receiving lenalidomide and dexamethasone alone.[1] Hepatotoxicity resolved in 6 of 8 elotuzumab-treated patients and resulted in permanent discontinuance of therapy in 2 patients.[1]
Liver function tests should be evaluated periodically during therapy with the drug.[1] If grade 3 or greater elevations in ALT or AST occur, elotuzumab therapy should be interrupted.[1] Once the toxicity has completely resolved, resumption of elotuzumab therapy may be considered.[1]
Interference with Serum Protein Electrophoresis and Immunofixation Assays
Elotuzumab is a human IgG kappa immunoglobulin; therefore, the drug may be detected on serum protein electrophoresis (SPEP) and immunofixation (IFE) assays, particularly in patients with IgA, IgM, IgD, or lambda light chain-restricted endogenous monoclonal immunoglobulins (M-protein).[1] Elotuzumab also comigrates with IgG kappa M-protein; therefore, the drug may mask clearance of endogenous M-protein resulting in false-positive SPEP and IFE assay results and misinterpretation of tumor response.[1][15]
Immunogenicity
There is potential for immunogenicity with the use of therapeutic proteins such as elotuzumab.[1][2] Anti-elotuzumab antibodies were detected by electrochemiluminescent immunoassay in 72 of 390 patients (18.5%) treated with elotuzumab in clinical studies.[1][2][10] In 63 (88%) of these patients, anti-elotuzumab antibodies developed during the first 2 months of elotuzumab therapy; anti-elotuzumab antibodies were resolved by 2-4 months in 49 (78%) of these patients.[1] In the ELOQUENT-2 study, neutralizing antibodies were detected in 19 of 299 patients (6%).[1]
Specific Populations
Pregnancy
There are no adequate and well-controlled studies of elotuzumab in pregnant women.[1] Animal reproduction studies have not been performed to date with the drug.[1]
Because elotuzumab is administered in combination with lenalidomide and dexamethasone, clinicians must consider that lenalidomide is contraindicated in pregnant women.[1][5] (See Combination Therapy under Cautions: Warnings/Precautions.)
Lactation
It is not known whether elotuzumab is distributed into milk.[1] Because of the potential for serious adverse reactions in nursing infants, women should be advised to discontinue nursing during combination therapy with elotuzumab, lenalidomide, and dexamethasone.[1] The effects of elotuzumab on nursing infants or on milk production are unknown.[1]
Pediatric Use
Safety and efficacy of elotuzumab have not been established in pediatric patients.[1]
Geriatric Use
In the phase 3 clinical trial evaluating elotuzumab in combination with lenalidomide and dexamethasone for the treatment of relapsed or refractory multiple myeloma, 57% of patients were 65 years of age or older.[1] No overall differences in safety or efficacy were observed between geriatric patients and younger adults.[1]
Hepatic Impairment
The pharmacokinetic profile of elotuzumab has not been established in patients with moderate to severe hepatic impairment.[1]
In a population pharmacokinetic analysis, systemic exposure to elotuzumab in patients with mild hepatic impairment was similar to that observed in patients with normal hepatic function.[1][6]
Renal Impairment
In a population pharmacokinetic analysis, systemic exposure to elotuzumab in patients with severe renal impairment (creatinine clearance less than 30 mL/minute) or end-stage renal disease requiring dialysis was similar to that observed in patients with normal renal function.[1][6][13]
Common Adverse Effects
Adverse effects reported in 10% or more of patients receiving elotuzumab in combination with lenalidomide and dexamethasone for the treatment of previously treated multiple myeloma and at an incidence that is at least 5% higher than that reported with lenalidomide and dexamethasone alone include fatigue,[1][2] diarrhea,[1][2] pyrexia,[1][2] constipation,[1][2] cough,[1][2] peripheral neuropathy,[1] nasopharyngitis,[1][2] upper respiratory tract infection,[1] loss of appetite,[1] pneumonia,[1] extremity pain,[1] headache,[1] vomiting,[1] weight loss,[1] lymphopenia,[1] cataracts,[1] and oropharyngeal pain.[1]
Laboratory abnormalities reported in 10% or more of patients receiving elotuzumab in combination with lenalidomide and dexamethasone and at an incidence that is at least 5% higher than that reported with lenalidomide and dexamethasone alone include lymphopenia,[1] leukopenia,[1] thrombocytopenia,[1][2] hypoalbuminemia,[1] elevated concentrations of alkaline phosphatase,[1] hyperglycemia,[1] hypocalcemia,[1] decreased serum bicarbonate concentrations,[1] and hyperkalemia.[1]
Drug Interactions
No formal drug interactions studies have been performed to date.[1]
Description
Elotuzumab, a recombinant humanized monoclonal antibody that is an antagonist of signaling lymphocytic activation molecule (SLAM) family member 7 (SLAMF7), is an antineoplastic agent;[1][6] the drug also is referred to as an anti-CS1 (anti-CD2 subset 1) monoclonal antibody.[2][10][11][12][16] The drug is an IgG1 kappa immunoglobulin produced by recombinant DNA technology in NS0 mouse myeloma-based cell culture.[1][6][7] Elotuzumab binds specifically to SLAMF7, a glycoprotein expressed on the surface of normal and malignant plasma cells, natural killer (NK) cells, and, at lower levels, specific immune cell subsets of differentiated cells within the hematopoietic lineage (e.g., CD8+ T cells[8][16] ).[1][9][11][16] Following binding of elotuzumab to SLAMF7 on myeloma cells and direct activation of NK cells via the SLAMF7 pathway, the Fc domain triggers host immune responses (i.e., antibody-dependent cell-mediated cytotoxicity [ADCC]) causing lysis of myeloma cells.[1][11][12][16] In preclinical models, concomitant use of elotuzumab and lenalidomide enhanced activation of NK cells compared with either drug alone and also demonstrated increased antitumor activity in vitro and in vivo.[1][12]
Areas under the serum concentration-time curve (AUCs) of elotuzumab are more than dose proportional over the dose range of 0.5-20 mg/kg, indicating target-mediated clearance.[1][6][10] Pharmacokinetic simulations indicate that following administration of elotuzumab 10 mg/kg IV once weekly for two 28-day cycles followed by 10 mg/kg IV every 2 weeks thereafter, plasma concentrations of elotuzumab increase for approximately 8 weeks after initiation of elotuzumab administration and steady-state concentrations are reached by 2-4 weeks following initiation of administration every 2 weeks.[6] Within about 3 months (geometric mean: 82.4 days) following discontinuance of combination therapy with elotuzumab, lenalidomide, and dexamethasone, elotuzumab concentrations are predicted to decline by approximately 97% from peak steady-state values.[1][17]
Data from a population pharmacokinetic analysis indicate that age (25-88 years), gender, race, baseline LDH concentrations, and albumin concentrations do not have clinically important effects on the pharmacokinetics of elotuzumab.[1][6][17]
Advice To Patients
Risk of infusion-related reactions; importance of reporting signs and symptoms of such reactions, including fever, chills, rash, or breathing difficulty, that occur during or within 24 hours of an infusion of the drug.[1] Importance of taking premedications as directed to minimize risk of infusion-related reactions.[1]
Risk of fetal harm when used in combination with lenalidomide.[1] Importance of advising women of childbearing potential and men who are partners of such women to take precautions to avoid fetal exposure to lenalidomide.[1] (See Combination Therapy under Cautions: Warnings/Precautions.) Importance of women informing a clinician immediately if they are or plan to become pregnant.[1]
Importance of advising women to avoid breast-feeding while receiving elotuzumab.[1] Importance of women informing a clinician if they plan to breast-feed.[1]
Risk of infection.[1] Importance of reporting signs or symptoms of infection (e.g., cough, fever, flu-like symptoms, shortness of breath, painful rash, burning on urination).[1]
Risk of developing a second primary malignancy.[1]
Risk of hepatotoxicity and importance of periodic liver function test monitoring.[1] Importance of reporting any manifestations of hepatotoxicity (e.g., jaundice, weakness, loss of appetite, fatigue, confusion, abdominal swelling, unusually colored stool).[1]
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.[1]
Importance of informing patients of other important precautionary information.[1] (See Cautions.)
Preparations
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.
Distribution of elotuzumab is restricted.[4] (See Restricted Distribution Program under Dosage and Administration: General.)
| Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
| Parenteral | For injection, for IV infusion | 300 mg | Empliciti® | Bristol-Myers Squibb |
| 400 mg | Empliciti® | Bristol-Myers Squibb |
1. Bristol-Myers Squibb. Empliciti® (elotuzumab) for injection prescribing information. Princeton, NJ; 2015 Nov.
2. Lonial S, Dimopoulos M, Palumbo A et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015; 373:621-31. (DOI: 10.1056/NEJMoa1505654) (PubMed: 26035255)
3. Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. Accessed 2016 Jun 10. (http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm)
4. Bristol-Myers Squibb. How to order empliciti. From Bristol-Myers Squibb for US Healthcare Professionals website. Accessed 2016 Jun 8. (http://www.emplicitihcp.com/ordering)
5. Celgene. Revlimid® (lenalidomide) capsules prescribing information. Summit, NJ; 2015 Feb.
6. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 761035Orig1s000: Clinical pharmacology and biopharmaceutics review(s). From FDA website. (http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/761035Orig1s000ClinPharmR.pdf)
7. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 761035Orig1s000: Chemistry review(s). From FDA website. (http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/761035Orig1s000ChemR.pdf)
8. Lonial S, Vij R, Harousseau JL et al. Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma. J Clin Oncol. 2012; 30:1953-9. (DOI: 10.1200/JCO.2011.37.2649) (PubMed: 22547589)
9. Guo H, Cruz-Munoz ME, Wu N et al. Immune cell inhibition by SLAMF7 is mediated by a mechanism requiring src kinases, CD45, and SHIP-1 that is defective in multiple myeloma cells. Mol Cell Biol. 2015; 35:41-51. (DOI: 10.1128/MCB.01107-14) (PubMed: 25312647)
10. Zonder JA, Mohrbacher AF, Singhal S et al. A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma. Blood. 2012; 120:552-9. (DOI: 10.1182/blood-2011-06-360552) (PubMed: 22184404)
11. Collins SM, Bakan CE, Swartzel GD et al. Elotuzumab directly enhances NK cell cytotoxicity against myeloma via CS1 ligation: evidence for augmented NK cell function complementing ADCC. Cancer Immunol Immunother. 2013; 62:1841-9. (DOI: 10.1007/s00262-013-1493-8) (PubMed: 24162108)
12. Balasa B, Yun R, Belmar NA et al. Elotuzumab enhances natural killer cell activation and myeloma cell killing through interleukin-2 and TNF-α pathways. Cancer Immunol Immunother. 2015; 64:61-73. (DOI: 10.1007/s00262-014-1610-3) (PubMed: 25287778)
13. Berdeja J, Jagannath S, Zonder J et al. Pharmacokinetics and safety of elotuzumab combined with lenalidomide and dexamethasone in patients with multiple myeloma and various levels of renal impairment: results of a phase Ib study. Clin Lymphoma Myeloma Leuk. 2016; 16:129-38. (DOI: 10.1016/j.clml.2015.12.007) (PubMed: 26795075)
14. Richardson PG, Jagannath S, Moreau P et al. Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma: final phase 2 results from the randomised, open-label, phase 1b-2 dose-escalation study. Lancet Haematol. 2015; 2:e516-27. (DOI: 10.1016/S2352-3026(15)00197-0) (PubMed: 26686406)
15. Afifi S, Michael A, Lesokhin A. Immunotherapy: A new approach to treating multiple myeloma with daratumumab and elotuzumab. Ann Pharmacother. 2016; 50:555-68. (DOI: 10.1177/1060028016642786) (PubMed: 27083916)
16. Lonial S, Kaufman J, Laubach J et al. Elotuzumab: a novel anti-CS1 monoclonal antibody for the treatment of multiple myeloma. Expert Opin Biol Ther. 2013; 13:1731-40. (DOI: 10.1517/14712598.2013.847919) (PubMed: 24151843)
17. Gibiansky L, Passey C, Roy A et al. Model-based pharmacokinetic analysis of elotuzumab in patients with relapsed/refractory multiple myeloma. J Pharmacokinet Pharmacodyn. 2016; 43:243-57. (DOI: 10.1007/s10928-016-9469-x) (PubMed: 26993283)
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