area of expertise [90:<60 bpm 66 31.3 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity to Empliciti. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to Empliciti in the studies described below with the incidences of antibodies in other studies or to other products may be misleading. Of 390 patients across four clinical studies who were treated with Empliciti and evaluable for the presence of anti-product antibodies, 72 patients (18.5%) tested positive for treatment-emergent anti-product antibodies by an electrochemiluminescent (ECL) assay. In 63 (88%) of these 72 patients, anti-product antibodies occurred within the first 2 months of the initiation of Empliciti treatment. Anti-product antibodies resolved by 2 to 4 months in 49 (78%) of these 63 patients. Neutralizing antibodies were detected in 19 of 299 patients in the randomized trial in multiple myeloma. Drug Interactions Drug Interactions For important drug interactions involving lenalidomide and dexamethasone, refer to their respective prescribing information. Laboratory Test Interference Empliciti may be detected in the SPEP and serum immunofixation assays of myeloma patients and could interfere with correct response classification. A small peak in the early gamma region on SPEP that is IgGƙ on serum immunofixation may potentially be attributed to Empliciti, particularly in patients whose endogenous myeloma protein is IgA, IgM, IgD, or lambda light chain restricted. This interference can impact the determination of complete response and possibly relapse from complete response in patients with IgG kappa myeloma protein [ see Warnings and Precautions (5.3) ]. USE IN SPECIFIC POPULATIONS Pregnancy Risk Summary There are no studies with Empliciti with pregnant women to inform any drug associated risks. Animal reproduction studies have not been conducted with elotuzumab. Empliciti 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. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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. Lactation Risk Summary There is no information on the presence of Empliciti 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 and dexamethasone, breastfeeding is not recommended. Refer to the lenalidomide and dexamethasone prescribing information for additional information. Females and Males of Reproductive Potential Pregnancy Testing Refer to the lenalidomide labeling for pregnancy testing requirements prior to initiating treatment in females of reproductive potential. When Empliciti 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. Contraception Refer to the lenalidomide labeling for contraception requirements prior to initiating treatment in females of reproductive potential and males. 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. Pediatric Use Safety and effectiveness have not been established in pediatric patients. Geriatric Use 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). Overdosage The dose of Empliciti at which severe toxicity occurs is not known. Empliciti does not appear to be removed by dialysis as determined in a study of patients with renal impairment. In case of overdosage, monitor patients closely for signs or symptoms of adverse reactions and institute appropriate symptomatic treatment. Empliciti Description Elotuzumab is a humanized recombinant monoclonal antibody directed to SLAMF7, a cell surface glycoprotein. Elotuzumab consists of the complementary determining regions (CDR) of the mouse antibody, MuLuc63, grafted onto human IgG1 heavy and kappa light chain frameworks. Elotuzumab is produced in NS0 cells by recombinant DNA technology. Elotuzumab has a theoretical mass of 148.1 kDa for the intact antibody. Empliciti (elotuzumab) is a sterile, nonpyrogenic, preservative-free lyophilized powder that is white to off-white, whole or fragmented cake in single-dose vials. Empliciti for Injection is supplied as 300 mg per vial and 400 mg per vial and requires reconstitution with Sterile Water for Injection, USP (13 mL and 17 mL, respectively) to obtain a solution with a concentration of 25 mg/mL. After reconstitution, each vial contains overfill to allow for withdrawal of 12 mL (300 mg) and 16 mL (400 mg). The reconstituted solution is colorless to slightly yellow, clear to slightly opalescent. Prior to intravenous infusion, the reconstituted solution is diluted with 230 mL of either 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP [ see Dosage and Administration (2.4) ]. Each 300 mg single-dose vial of Empliciti also contains the following inactive ingredients: citric acid monohydrate (2.44 mg), polysorbate 80 (3.4 mg), sodium citrate (16.6 mg), and sucrose (510 mg). Each 400 mg single-dose vial of Empliciti also contains the following inactive ingredients: citric acid monohydrate (3.17 mg), polysorbate 80 (4.4 mg), sodium citrate (21.5 mg), and sucrose (660 mg). Empliciti - Clinical Pharmacology 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. 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 . Pharmacodynamics Cardiac Electrophysiology Empliciti does not prolong the QT interval to any clinically relevant extent when administered with lenalidomide and dexamethasone at the recommended dose or as monotherapy (at a dose 2 times the recommended dose). Pharmacokinetics Elotuzumab exhibits nonlinear pharmacokinetics (PK) resulting in greater than proportional increases in area under the concentration-time curve (AUC) indicative of target-mediated clearance. The administration of the recommended 10 mg/kg Empliciti regimen with lenalidomide and dexamethasone is predicted to result in geometric mean (CV%) steady-state trough concentrations of 194 μg/mL (52%). Elimination The clearance of elotuzumab decreased from a geometric mean (CV%) of 17.5 (21.2%) to 5.8 (31%) mL/day/kg with an increase in dose from 0.5 (i.e., 0.05 times the recommended dosage) to 20 mg/kg (i.e., 2 times the recommended dosage). When elotuzumab is administered with lenalidomide and dexamethasone, approximately 97% of the maximum steady-state concentration is predicted to be eliminated with a geometric mean (CV%) of 82.4 (48%) days. Specific Populations Clinically significant differences were not observed in the PK of elotuzumab based on age (37 to 88 years), sex, race, baseline lactate dehydrogenase, albumin, renal impairment (creatinine clearance (CLcr) 15 to 89 mL/min), end-stage renal disease (CLcr> <15 mL/min) with or without hemodialysis, and mild hepatic impairment (total bilirubin upper limit of normal (ULN) and aspartate transaminase (AST) > ULN OR total bilirubin 1 to 1.5 times the ULN and AST any value). The PK of elotuzumab in patients with moderate (total bilirubin > 1.5 to 3 times the ULN and AST any value) to severe (total bilirubin > 3 times the ULN and AST any value) hepatic impairment is unknown. The clearance of elotuzumab increased with increasing body weight supporting a weight-based dose. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment of Fertility No carcinogenicity or mutagenicity data are available for elotuzumab in animals or humans. Fertility studies have not been performed for elotuzumab. Clinical Studies The efficacy and safety of Empliciti in combination with lenalidomide and dexamethasone were evaluated in a randomized, open-label trial in patients with multiple myeloma who had received one to three prior therapies and had documented progression following their most recent therapy. Eligible patients were randomized in a 1:1 ratio to receive either Empliciti in combination with lenalidomide and low-dose dexamethasone or lenalidomide and low-dose dexamethasone. Treatment was administered in 4-week cycles until disease progression or unacceptable toxicity. Empliciti 10 mg/kg was administered intravenously each week for the first 2 cycles and every 2 weeks thereafter. Prior to Empliciti infusion, dexamethasone was administered as a divided dose: an oral dose of 28 mg and an intravenous dose of 8 mg. In the control group and on weeks without Empliciti, dexamethasone 40 mg was administered as a single oral dose weekly. Lenalidomide 25 mg was taken orally once daily for the first 3 weeks of each cycle. Assessment of tumor response was conducted every 4 weeks. A total of 646 patients were randomized to receive treatment: 321 to Empliciti in combination with lenalidomide and low-dose dexamethasone and 325 to lenalidomide and low-dose dexamethasone. Demographics and baseline disease characteristics were balanced between treatment arms. The median age was 66 years (range, 37-91); 57% of patients were 65 years or older; 60% of patients were male; whites comprised 84% of the study population, Asians 10%, and blacks 4%. The ECOG performance status was 0 in 47%, 1 in 44%, and 2 in 9% of patients, and ISS Stage was I in 43%, II in 32%, and III in 21% of patients. The cytogenetic categories of del 17p and t(4;14) were present in 32% and 9% of patients, respectively. The median number of prior therapies was 2. Thirty-five percent (35%) of patients were refractory (progression during or within 60 days of last therapy) and 65% were relapsed (progression after 60 days of last therapy). Prior therapies included stem cell transplant (55%), bortezomib (70%), melphalan (65%), thalidomide (48%), and lenalidomide (6%). The efficacy of Empliciti was evaluated by progression-free survival (PFS) as assessed by hazard ratio, and overall response rate (ORR) as determined by a blinded Independent Review Committee using the European Group for Blood and Marrow Transplantation (EBMT) response criteria. Efficacy results are shown in Table 7 and Figure 1. The median number of treatment cycles was 19 for the Empliciti group and 14 for the comparator arm with a minimum follow-up of two years. Overall survival (OS) results at interim analysis are shown in Table 7 and Figure 2. The OS results at interim analysis did not reach statistical significance. Table 7: Efficacy Results Empliciti + Lenalidomide/ Dexamethasone N=321 Lenalidomide/ Dexamethasone N=325 PFS * p-value based on the log-rank test stratified by ß2 microglobulins (> <3.5 mg/L vs ≥3.5 mg/L), number of prior lines of therapy (1 vs 2 or 3), and prior immunomodulatory therapy (no vs prior thalidomide only vs other). † European Group for Blood and Marrow Transplantation (EBMT) criteria. ‡ p-value based on the Cochran-Mantel-Haenszel chi-square test stratified by ß2 microglobulins (> <3.5 mg/L vs ≥3.5 mg/L), number of prior lines of therapy (1 vs 2 or 3), and prior immunomodulatory therapy (no vs prior thalidomide only vs other). Complete response (CR) + stringent complete response (sCR). Empliciti s interference with the assessment of myeloma protein with immunofixation and serum protein electrophoresis assay may interfere with correct response classification [see Drug Interactions (7) ]. g A pre-specified interim analysis for OS was performed based on a minimum follow-up time of 35.4 months. Hazard Ratio [95% CI] 0.70 [0.57, 0.85] Stratified log-rank test p-value* 0.0004 Median PFS in months [95% CI] 19.4 [16.6, 22.2] 14.9 [12.1, 17.2] Response Overall Response (ORR) † n (%) [95% CI] 252 (78.5) [73.6, 82.9] 213 (65.5) [60.1, 70.7] p-value ‡ 0.0002 Complete Response (CR + sCR) †, n (%) 14 (4.4) 24 (7.4) Very Good Partial Response (VGPR) † n (%) 91 (28.3) 67 (20.6) Partial Response (PR) † n (%) 147 (45.8) 122 (37.5) Overall Survival g Hazard Ratio [95% CI] 0.77 [0.61, 0.97] Median OS in months [95% CI] 43.7 [40.3, NE] 39.6 [33.3, NE] Figure 1: Progression-Free Survival The 1- and 2-year rates of PFS for Empliciti in combination with lenalidomide and dexamethasone treatment were 68% and 41%, respectively, compared with 57% and 27%, respectively, for lenalidomide and dexamethasone treatment. Figure 2: Study 1 Overall Survival How Supplied/Storage and Handling Empliciti (elotuzumab) is white to off-white lyophilized powder available as follows: Carton Content NDC One 300 mg single-dose vial 0003-2291-11 One 400 mg single-dose vial 0003-4522-11 Store Empliciti under refrigeration at 2 C to 8 C (36 F-46 F). Protect Empliciti from light by storing in the original package until time of use. Do not freeze or shake. Patient Counseling Information Advise the patient to read the FDA-approved patient labeling (Patient Information) . Infusion Reactions • Empliciti 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 [ see Warnings and Precautions (5.1) ]. • Advise patients that they will be required to take the following oral medications prior to Empliciti dosing to reduce the risk of infusion reaction [ see Dosage and Administration (2.2) ]: • Dexamethasone orally as prescribed • H1 blocker: diphenhydramine or equivalent (if oral) • H2 blocker: ranitidine or equivalent (if oral) • Acetaminophen (650 to 1000 mg orally) Pregnancy • 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 [ see Use in Specific Populations (8.1) ]. Infections • Inform patients of the risk of developing infections during treatment with Empliciti, and to report any symptoms of infection [ see Warnings and Precautions (5.2) ]. Second Primary Malignancies • Inform patients of the risk of developing SPM during treatment with Empliciti [ see Warnings and Precautions (5.3) ]. Hepatotoxicity • Inform patients of the risk of hepatotoxicity during treatment with Empliciti and to report any signs and symptoms associated with this event to their healthcare provider for evaluation [ see Warnings and Precautions (5.4) ]. Patient Information Empliciti (em-plis-city) (elotuzumab) for injection Empliciti is used with two other prescription medicines called REVLIMID (lenalidomide) and dexamethasone. Read the Medication Guide that comes with REVLIMID. You can ask your healthcare provider or pharmacist for information about dexamethasone. What is Empliciti? Empliciti is a prescription medicine used to treat multiple myeloma in combination with the medicines REVLIMID (lenalidomide) and dexamethasone in people who have received one to three prior treatments for their multiple myeloma. It is not known if Empliciti is safe and effective in children. Before you receive Empliciti, tell your healthcare provider about all of your medical conditions, including if you: • have an infection • are pregnant or plan to become pregnant. It is not known if Empliciti may harm your unborn baby. However, REVLIMID may cause birth defects or death of an unborn baby. o Before receiving Empliciti with REVLIMID and dexamethasone, females and males must agree to the instructions in the REVLIMID REMS program. The REVLIMID REMS program has specific requirements about birth control (contraception), pregnancy testing, blood donation, and sperm donation that you need to know. Talk to your healthcare provider to learn more about REVLIMID. • are breastfeeding or plan to breastfeed. It is not known if Empliciti passes into breast milk. You should not breastfeed during treatment with Empliciti and REVLIMID and dexamethasone. • Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. How will I receive Empliciti? • Empliciti will be given to you by intravenous (IV) infusion into your vein. • Your Empliciti treatment schedule is divided into cycles that are 28 days (4 weeks) long. A cycle includes the number of days you are on treatment and also the time you spend resting in between treatments. • Empliciti with REVLIMID and dexamethasone is usually given as follows: o Cycles 1 and 2 (28 days per cycle), you will receive Empliciti one time every week. o Cycles 3 and up (28 days per cycle), you will receive Empliciti one time every 2 weeks. • Your healthcare provider will decide how many treatments you will receive. • Before every Empliciti infusion, you will receive medicines to help reduce the risk of infusion reactions. • If you miss any appointments call your healthcare provider as soon as possible. What are the possible side effects of Empliciti? Empliciti may cause serious side effects, including: • Infusion reactions. Infusion reactions can happen during your infusion or within 24 hours after your infusion of Empliciti. Your healthcare provider will give you medicines before each infusion of Empliciti to help reduce the risk of an infusion reaction. If you have an infusion reaction while receiving Empliciti, your healthcare provider will slow or stop your infusion and treat your reaction. If you have a severe infusion reaction, your healthcare provider may stop your treatment completely. Tell your healthcare provider or get medical help right away if you have any of these symptoms after your infusion with Empliciti: o fever o chills o rash o trouble breathing o dizziness o light-headedness • Infections. People with multiple myeloma who receive Empliciti with REVLIMID and dexamethasone may develop infections that can be serious. Tell your healthcare provider right away if you have any signs and symptoms of an infection, including: o fever o flu-like symptoms o cough o shortness of breath o burning with urination o a painful skin rash • Risk of new cancers (malignancies). People with multiple myeloma who receive Empliciti with REVLIMID and dexamethasone have a risk of developing new cancers. Talk with your healthcare provider about your risk of developing new cancers if you receive Empliciti. Your healthcare provider will check you for new cancers during your treatment with Empliciti. • Liver problems. Empliciti may cause liver problems. Your healthcare provider will do blood tests to check your liver during treatment with Empliciti. Tell your healthcare provider if you have signs and symptoms of liver problems, including: tiredness, weakness, loss of appetite, yellowing of your skin or eyes, color changes in your stools, confusion, or swelling of the stomach area. The most common side effects of Empliciti include: • fatigue • diarrhea • fever • constipation • cough • numbness, weakness, tingling, or burning pain in your arms or legs • sore throat or runny nose • upper respiratory tract infection • decreased appetite • pneumonia These are not all of the possible side effects of Empliciti. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Bristol-Myers Squibb at 1-800-721-5072. General information about the safe and effective use of Empliciti Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your pharmacist or healthcare provider for information about Empliciti that is written for health professionals. What are the ingredients of Empliciti? Active ingredient: elotuzumab Inactive ingredients: citric acid monohydrate, polysorbate 80, sodium citrate, sucrose For more information, call 1-844-Empliciti (844-367-5424) or visit Empliciti.com. Empliciti is a trademark of Bristol-Myers Squibb Company. REVLIMID is a registered trademark and REVLIMID REMS is a trademark of Celgene Corporation. Manufactured by: Bristol-Myers Squibb Company, Princeton, NJ 08543 USA U.S. License No. 1713 This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 5/2017 Empliciti 300 mg Representative Packaging NDC 0003-2291-11 Rx only Empliciti TM (elotuzumab) for Injection 300 mg per vial For intravenous Infusion Only Reconstitute and Further Dilute Prior to Use Single-Dose Vial. Discard Unused Portion. Bristol-Myers Squibb Empliciti 400 mg Representative Packaging NDC 0003-4522-11 Rx only Empliciti TM (elotuzumab) for Injection 400 mg per vial For intravenous Infusion Only Reconstitute and Further Dilute Prior to Use Single-Dose Vial. Discard Unused Portion. Bristol-Myers Squibb Empliciti elotuzumab injection, powder, lyophilized, for solution Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0003-2291 Route of Administration INTRAVENOUS DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ELOTUZUMAB (ELOTUZUMAB) ELOTUZUMAB 300 mg Inactive Ingredients Ingredient Name Strength CITRIC ACID MONOHYDRATE 2.44 mg POLYSORBATE 80 3.4 mg SODIUM CITRATE, UNSPECIFIED FORM 16.6 mg SUCROSE 510 mg Packaging # Item Code Package Description 1 NDC:0003-2291-11 1 VIAL, SINGLE-USE in 1 CARTON 1 1 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION in 1 VIAL, SINGLE-USE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date BLA BLA761035 11/30/2015 Empliciti elotuzumab injection, powder, lyophilized, for solution Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0003-4522 Route of Administration INTRAVENOUS DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ELOTUZUMAB (ELOTUZUMAB) ELOTUZUMAB 400 mg Inactive Ingredients Ingredient Name Strength CITRIC ACID MONOHYDRATE 3.17 mg POLYSORBATE 80 4.4 mg SODIUM CITRATE, UNSPECIFIED FORM 21.5 mg SUCROSE 660 mg Packaging # Item Code Package Description 1 NDC:0003-4522-11 1 VIAL, SINGLE-USE in 1 CARTON 1 1 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION in 1 VIAL, SINGLE-USE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date BLA BLA761035 11/30/2015 Labeler - E.R. Squibb & Sons, L.L.C. (011550092) Revised: 05/2017 E.R. Squibb & Sons, L.L.C. Next Interactions Print this page Add to My Med List More about Empliciti (elotuzumab) Side Effects During Pregnancy Dosage Information Drug Interactions Support Group Pricing & Coupons En Español 0 Reviews Add your own review/rating Drug class: miscellaneous antineoplastics Consumer resources Empliciti Empliciti (Advanced Reading) Professional resources Empliciti (AHFS Monograph) Related treatment guides Multiple Myeloma> ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Manufacturers Bristol-Myers Squibb Company AbbVie Inc. Drug Class Miscellaneous antineoplastics Related Drugs miscellaneous antineoplastics tretinoin , Revlimid , Zytiga , Accutane , isotretinoin , irinotecan Multiple Myeloma dexamethasone , Decadron , Revlimid , cyclophosphamide , Cytoxan , Adriamycin , doxorubicin , Velcade , Doxil , vincristine , lenalidomide , Pomalyst , thalidomide , bortezomib , carfilzomib , Kyprolis , Ninlaro , daratumumab , melphalan , Thalomid , Dexasone , pomalidomide , carmustine , ixazomib , More... Empliciti Rating No Reviews - Be the first! No Reviews - Be the first! Not Rated - Be the first!} } a chosen
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