Elotuzumab

Elotuzumab is used for: Multiple myeloma

Multiple Myeloma Indicated in combination with lenalidomide and dexamethasone for multiple myeloma in patients who have received 1-3 prior therapies 10 mg/kg IV qWeek for first two 28-day cycles; thereafter, administer 10 mg/kg IV q2Week (on days 1 and 15) Continue treatment until disease progression or unacceptable toxicity Hepatic impairment Mild: No dose adjustment required Moderate-to-severe: Not studied

Renal impairment Mild-to-severe (CrCl 15-89 mL/min) or ESRD (CrCl <15 mL/min) with or without hemodialysis: No dose adjustment required

IV Preparation Reconstitution Calculate the dose (mg) and determine the number of vials needed for the 10-mg/kg dosage based on patient weight Reconstitute vial with sterile water for injection (SWI) Aseptically reconstitute each vial with a syringe of adequate size and an 18-gauge or smaller needle Hold the vial upright and swirl the solution by rotating the vial to dissolve the lyophilized cake Invert the vial a few times in order to dissolve any powder that may be present on top of the vial or the stopper Avoid vigorous agitation; DO NOT SHAKE The lyophilized powder should dissolve in <10 minutes After the remaining solids are completely dissolved, allow the reconstituted solution to stand for 5-10 minutes The reconstituted preparation results in a colorless to slightly yellow, clear to slightly opalescent solution Inspect visually for particulate matter and discoloration prior to administration, whenever solution and container permit Discard the solution if any particulate matter or discoloration is observed 300-mg vial reconstitution SWI required for reconstitution: 13 mL Deliverable volume of reconstituted drug in vial: 12 mL Postreconstitution concentration: 25 mg/mL 400-mg vial SWI required for reconstitution: 17 mL Deliverable volume of reconstituted drug in vial: 16 mL Postreconstitution concentration: 25 mg/mL Dilution Once the reconstitution is completed, withdraw the necessary volume for the calculated dose from each vial, up to a maximum of 16 mL from 400-mg vial and 12 mL from 300-mg vial Further dilute with 230 mL of either 0.9% NaCl or D5W into an infusion bag made of polyvinyl chloride or polyolefin The volume of 0.9% NaCl or D5W can be adjusted so as not to exceed 5 mL/kg of patient weight at any given dose of elotuzumab IV Administration Administer the entire dose with an infusion set and a sterile, nonpyrogenic, low protein-binding filter (with a pore size of 0.2-1.2 micrometer) using an automated infusion pump Do not mix or administer with other medicinal products Complete IV infusion within 24 hr of reconstitution and dilution IV infusion rate Initiate IV infusion at a rate of 0.5 mL/min; may increase infusion rate in a stepwise fashion described below; not to exceed 5 mL/min Adjust rate if infusion reaction ?grade 2 occurs Cycle 1, dose 1 0-30 min: 0.5 mL/min 30-60 min: 1 mL/min ?60 min: 2 mL/min Cycle 1, dose 2 0-30 min: 3 mL/min ?30 min: 4 mL/min Cycle 1, dose 3 and 4 and all subsequent cycles 5 mL/min Premedication Complete administration of the following premedications 45-90 min before elotuzumab infusion Dexamethasone 8 mg IV Diphenhydramine 25-50 mg PO or IV (or equivalent H1 blocker) Ranitidine 50 mg IV (or equivalent H2 blocker) Acetaminophen 650-1000 mg PO

None for elotuzumab

Infusion reactions can occur and may include fever, chills, and hypertension (see Dosage Modifications) Infections reported, including opportunistic infections (eg, fungal infections, herpes zoster) Second primary malignancies reported, including solid tumors and skin cancers Elevations in liver enzymes (AST/ALT >3 x ULN, TB >2 x ULN, and alkaline phosphatase <2 x ULN) consistent with hepatotoxicity were reported; monitor liver enzymes periodically; stop elotuzumab for ≥grade 3 elevation of liver enzymes; may consider treatment continuation after return to baseline values

Pregnancy No available data on use in pregnant women to inform a drug associated risk of major birth defects and miscarriage Therapy is administered in combination with lenalidomide and dexamethasone or pomalidomide and dexamethasone, which can cause embryo-fetal harm and are contraindicated for use in pregnancy; refer to lenalidomide, pomalidomide and dexamethasone prescribing information for additional information; lenalidomide and pomalidomide are only available through REMS program Contraception Refer to lenalidomide and pomalidomide labeling for contraception requirements prior to initiating treatment in females of reproductive potential Lactation There are no data on presence of drug in human milk, effects on breastfed child, or on milk production; because of potential for serious adverse reactions in breastfed child from elotuzumab Administered in combination with lenalidomide and dexamethasone or pomalidomide and dexamethasone, advise lactating women not to breastfeed during treatment; refer to lenalidomide, pomalidomide and dexamethasone

Side effects of Elotuzumab : >10% Heart rate <60 bpm (66%) Fatigue (61.1%) Heart rate ≥100 bpm (47.8%) Diarrhea (46.9%) Pyrexia (37.4%) Cough (34.3%) Systolic blood pressure ≥160 mmHg (33.3%) Systolic blood pressure <90 mmHg (28.9%) Infections, grades 3-4 (28%) Peripheral neuropathy (26.7%) Nasopharyngitis (24.5%) Upper respiratory tract infection (22.6%) Opportunistic infections, all (22%) Decreased appetite (20.8%) Pneumonia (20.1%) Diastolic blood pressure ≥100 mmHg (17.3%) Pain in extremities (16.4%) Headache (15.4%) Vomiting (14.5%) Pneumonia, grades 3-4 (14.2%) Decreased weight (13.8%) Herpes zoster infections (13.5%) Lymphopenia (13.2%) Fatigue, grades 3-4 (12.6%) Cataracts (11.9%) Oropharyngeal pain (10.1%) 1-10% Infusion related reactions (10%) Fungal infections (9.7%) Secondary primary malignancies (9.1%) Lymphopenia, grades 3-4 (8.8%) Cataracts, grades 3-4 (6.3%) Diarrhea, grades 3-4 (5%) Peripheral neuropathy, grades 3-4 (3.8%) Pyrexia, grades 3-4 (2.5%) Hepatotoxicity (2.5%) Constipation, grades 3-4 (1.3%) Decreased weight, grades 3-4 (1.3%) Infusion reactions, grade 3 (1%)

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; 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 antitumor activity in vitro and in vivo