Dosing and uses of Empliciti (elotuzumab)
Adult dosage forms and strengths
injection, powder for reconstitution
- 300mg/vial
- 400mg/vial
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
Note: Premedicate before each dose (see Administration)
Lenalidomide and dexamethasone dosage regimen
- Lenalidomide: 25 mg PO qDay on days 1-21
- Dexamethasone (on days that elotuzumab is administered): 28 mg PO between 3 and 24 hr before elotuzumab dose plus 8 mg IV between 45 and 90 minutes before elotuzumab dose (IV dose is part of premedication regimen)
- Dexamethasone (on days that elotuzumab is NOT administered [days 8 and 22 of cycle 3 and all subsequent cycles]): 40 mg PO
Dosage modifications
If the dose of 1 drug in the regimen is delayed, interrupted, or discontinued, the treatment with the other drugs may continue as scheduled
If dexamethasone is delayed or discontinued, base the decision whether to administer elotuzumab on clinical judgment (ie, risk of hypersensitivity)
Dose delays and modifications for dexamethasone and lenalidomide should be performed as recommended in their prescribing information
Infusion reaction
- ≥Grade 2: Interrupt infusion and institute appropriate medical and supportive measures; upon resolution to ≤grade 1, restart at 0.5 mL/min and gradually increase at a rate of 0.5 mL/min q30min as tolerated to the rate at which the infusion reaction occurred; resume escalation if there is no recurrence of the infusion reaction
- If the infusion reaction recurs, stop the infusion and do not restart on that day
- In patients who experience an infusion reaction, monitor vital signs q30min for 2 hr after the end of the infusion
- Severe infusion reactions may require permanent discontinuation of therapy and emergency treatment
Renal impairment
- Mild-to-severe (CrCl 15-89 mL/min) or ESRD (CrCl <15 mL/min) with or without hemodialysis: No dose adjustment required
Hepatic impairment
- Mild: No dose adjustment required
- Moderate-to-severe: Not studied
Pediatric dosage forms and strengths
Safety and efficacy not established
Empliciti (elotuzumab) adverse (side) effects
Adverse reaction percentages listed are for all grades of toxicity unless otherwise stated
>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%)
Warnings
Contraindications
None for elotuzumaB
See lenalidomide and dexamethasone prescribing information
Cautions
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
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
Pregnancy and lactation
Pregnancy
There are no studies with elotuzumab with pregnant women to inform any drug associated risks
Animal reproduction studies have not been conducted with elotuzumaB
Lenalidomide (part of the combination regimen) can cause embryo-fetal harm and is contraindicated for use in pregnancy
Contraception
- Women of childbearing age and men with partners of childbearing potential must use effect contraception beginning 4 weeks prior to initiating treatment with lenalidomide, during treatment, treatment interruptions, and for 28 days following cessation of treatment with lenalidomide
- Females of reproductive potential must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously (1 highly effective form of contraception – tubal ligation, IUD, hormonal (birth control pills, injections, hormonal patches, vaginal rings or implants), or partner’s vasectomy and 1 additional effective contraceptive method – male latex or synthetic condom, diaphragm, or cervical cap
- Lenalidomide is present in the semen of males; therefore, males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking lenalidomide, during dose interruptions, and for up to 28 days after discontinuing lenalidomide, even if they have undergone a successful vasectomy
- Males taking lenalidomide must not donate sperm
Lactation
Unknown if distributed in human breast milk
Breast feeding is not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Empliciti (elotuzumab)
Mechanism of action
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
Pharmacokinetics
Trough concentration: 194 mcg/mL
Clearance: 17.5 mL/day/kg
Administration
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; not to exceed 2 mL/min
- Infusion rate titration
- 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 – 1 mL/min; &ge030 min – 2 mL/min
- Cycle 1, doses 3 and 4 and all subsequent cycles: 2 mL/min
- Infusion rate may be increased to a maximum of 5 mL/min in patients who have received 4 cycles of treatment
- Adjust the infusion rate following a grade 2 or higher infusion reaction
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
Storage
Unopened vials
- Refrigerate at 2-8ºC (36-46ºF)
- Protect from light by storing in the original package until time of use
- Do not freeze or shake
Diluted infusion
- Refrigerate at 2-8ºC (36-46ºF), protected from light, for up to 24 hr
- A maximum of 8 hr of the total 24 hr can be at room temperature 20-25ºC (68-77ºF) and room light
