Elotuzumab is a humanized IgG1 monoclonal antibody that specifically targets the Signaling Lymphocytic Activation Molecule Family member 7 (SLAMF7) protein, which is present on myeloma cells and natural killer cells. It is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received 1 to 3 prior therapies or in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor. Severe and fatal infection has been reported with elotuzumab therapy; monitor patients and treat infection promptly.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Emetic Risk
-Low
-Administer routine antiemetic prophylaxis prior to treatment.
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Premedication with acetaminophen PO, an IV or PO H1-blocker (e.g., diphenhydramine), an IV or PO H2-blocker, and IV dexamethasone is required prior to each infusion; hold therapy for grade 2 or higher infusion-related reactions.
-Do not mix with other drugs or infuse with other drugs through the same IV line.
Reconstitution:
-Calculate the appropriate dose and reconstitute (using an 18-gauge or smaller needle) the 300-mg vial with 13 mL of Sterile Water for injection and the 400-mg vial with 17 mL of Sterile Water for injection.
-Following reconstitution, each vial contains overfill to allow for a maximum withdrawal of 12 mL for the 300-mg vial and 16 mL for the 400-mg vial; the final vial concentration is 25 mg/mL.
-Swirl the solution by rotating the vial; invert the vial a few times to dissolve the powder. Do NOT agitate or shake to reconstitute.
-The lyophilized powder should dissolve within 10 minutes; allow the reconstituted solution to stand for 5 to 10 minutes after all powder is dissolved.
Dilution:
-Withdraw the appropriate amount (mL) from the elotuzumab 25 mg/mL vials for the calculated dose; do not exceed a maximum withdrawal of 12 mL for the 300-mg vial and of 16 mL for the 400-mg vial; discard any unused portion left in the vial.
-Add the calculated amount of elotuzumab to an infusion bag made of polyvinyl chloride or polyolefin and then add enough 0.9% Sodium Chloride for injection or 5% Dextrose injection so that the final diluted admixture concentration is between 1 and 6 mg/mL.
-Do NOT exceed 5 mL/kg of patient weight at any given dose.
-Storage following dilution: The diluted admixture may be stored for up to 24 hours when refrigerated (2 to 8 degrees C or 36 to 46 degrees F) and protected from light; a maximum of 8 hours (of the total 24 hours) may be at room temperature (20 to 25 degrees C or 68 to 77 degrees F).
Intravenous Infusion:
-Administer the diluted admixture using an infusion-set and a sterile, non-pyrogenic, low protein-binding filter (pore size of 0.2 to 1.2 micrometer); use an automated infusion pump.
-For the 10 mg/kg dose, administer the diluted infusion intravenously at the appropriate infusion rate as follows:
Cycle 1, dose 1: start at 0.5 mL/minute for 30 minutes, increase to 1 mL/minute for 30 minutes, then increase to a maximum rate of 2 mL/minute.
Cycle 1, dose 2: start at 3 mL/minute for 30 minutes, then increase to a maximum rate of 4 mL/minute.
Cycle 1, doses 3 and 4, and all subsequent cycles: 5 mL/minute; do not exceed this rate.
-For the 20 mg/kg dose, administer the diluted infusion intravenously at the appropriate infusion rate as follows:
Dose 1: start at 3 mL/minute for 30 minutes, then increase to a maximum rate of 4 mL/minute.
Dose 2 and all subsequent doses: 5 mL/minute; do not exceed this rate.
-Up-titration of the infusion rate may be considered only in the absence of infusion reactions.
-Complete the infusion within 24 hours from reconstitution.
Altered mood occurred in 5% or greater of patients with relapsed or refractory multiple myeloma who received elotuzumab in combination with lenalidomide and dexamethasone or pomalidomide and dexamethasone in clinical trials.
Infection was reported in relapsed or refractory multiple myeloma patients who received elotuzumab, lenalidomide, and dexamethasone in a clinical trial; some cases resulted in death. Monitor patients for signs and symptoms of infections; treat promptly if an infection develops. Infection (81% vs. 74%) including opportunistic infections (22% vs. 13%), fungal infections (10% vs. 5%), herpes zoster infection (14% vs. 7%), upper respiratory tract infection (23% vs. 17%), naso-pharyngitis (25% vs. 19%), and pneumonia (20% vs. 14%) occurred more often with elotuzumab, lenalidomide, and dexamethasone (n = 318) compared with lenalidomide and dexamethasone alone (n = 317) in patients with relapsed or refractory multiple myeloma in a randomized, phase 3 trial. Additionally, grade 3 and 4 infections (28%) including upper respiratory tract infection (0.6%) and pneumonia (14%) and fatal infections (2.5%) were reported in elotuzumab-treated patients. Opportunistic infections (10% vs. 9%), herpes zoster infection (5% vs. 1.8%), upper respiratory tract infection (17% vs. 9%), and pneumonia (18% vs. 13%) occurred more often with elotuzumab, pomalidomide, and dexamethasone (n = 60) compared with pomalidomide and dexamethasone alone (n = 55) in patients with relapsed or refractory multiple myeloma in a randomized, phase 2 trial; infection was reported in 65% of patients in both treatment arms. Additionally, grade 3 and 4 infections (13%) including pneumonia (10%) and fatal infections (5%) were reported in elotuzumab-treated patients. Types of pneumonia reported in these clinical trials were atypical pneumonia, bronchopneumonia, lobar pneumonia, bacterial pneumonia, fungal pneumonia, influenza pneumonia, and pneumococcal pneumonia.
New primary malignancy has been reported in patients with relapsed or refractory multiple myeloma who received elotuzumab in combination with lenalidomide and dexamethasone or pomalidomide and dexamethasone in clinical trials. Monitor patients for signs and symptoms of new primary malignancies. Invasive second primary malignancy (9% vs. 6%) including solid tumors (3.5% vs. 2.2%) and skin cancer (4.4% vs. 2.8%) occurred more often with elotuzumab, lenalidomide, and dexamethasone (n = 318) compared with lenalidomide and dexamethasone alone (n = 317) in patients with relapsed or refractory multiple myeloma in a randomized, phase 3 trial. Hematologic malignancies were reported in 1.6% of patients in each treatment arm. Invasive second primary malignancy was not reported in patients with relapsed or refractory multiple myeloma who received elotuzumab, pomalidomide, and dexamethasone (n = 60) in a randomized, phase 2 trial.
Hepatotoxicity (e.g., elevated hepatic enzymes, hyperbilirubinemia) was reported in relapsed or refractory multiple myeloma patients who received elotuzumab, lenalidomide, and dexamethasone in a clinical trial. Monitor liver function tests periodically. Hold elotuzumab in patients who develop grade 3 or higher elevated hepatic enzymes during therapy. Consider restarting elotuzumab therapy when hepatic enzymes return to baseline values. Hepatotoxicity (defined as an AST or ALT level greater than 3 times the upper limit of normal (ULN), a total bilirubin level greater than 2 times the ULN, and an alkaline phosphatase (AP) level less than 2 times the upper limit) occurred in 2.5% of patients who received elotuzumab, lenalidomide, and dexamethasone (n = 318) compared with 0.6% of patients who received lenalidomide and dexamethasone alone (n = 317) for the treatment of relapsed or refractory multiple myeloma in a randomized, phase 3 trial. In clinical trials, laboratory abnormalities that worsened from baseline included hypoalbuminemia (73%; grade 3 or 4, 3.9%) and elevated AP levels (39%; grade 3 or 4, 1.3%) in patients who received elotuzumab, lenalidomide, and dexamethasone (n = 318) and hypoalbuminemia (65%; grade 3 or 4, 1.7%) in patients who received elotuzumab, pomalidomide, and dexamethasone (n = 60).
Anorexia/decreased appetite (21% vs. 13%), constipation (36% vs. 27%), diarrhea (47% vs. 36%), and vomiting (14% vs. 9%) occurred more often with elotuzumab, lenalidomide, and dexamethasone (n = 318) compared with lenalidomide and dexamethasone alone (n = 317) in patients with relapsed or refractory multiple myeloma in a randomized, phase 3 trial; grade 3 and 4 anorexia (1.6%), constipation (1.3%), diarrhea (5%), and vomiting (0.3%) were also reported in elotuzumab-treated patients. Constipation (22% vs. 11%) and diarrhea (18% vs. 9%) occurred more often with elotuzumab, pomalidomide, and dexamethasone (n = 60) compared with pomalidomide and dexamethasone alone (n = 55) in patients with relapsed or refractory multiple myeloma in a randomized, phase 2 trial; grade 3 or 4 constipation was reported in 1.7% of elotuzumab-treated patients.
Lymphopenia (13% vs. 7%) and serious anemia (2.8% vs. 1.9%) occurred more often with elotuzumab, lenalidomide, and dexamethasone (n = 318) compared with lenalidomide and dexamethasone alone (n = 317) in patients with relapsed or refractory multiple myeloma in a randomized, phase 3 trial; grade 3 and 4 lymphopenia was reported in 9% of elotuzumab-treated patients. Lymphopenia occurred in 10% of patients who received elotuzumab, pomalidomide, and dexamethasone (n = 60) compared with 1.8% of patients who received pomalidomide and dexamethasone alone (n = 55) for the treatment of relapsed or refractory multiple myeloma in a randomized, phase 2 trial; grade 3 or 4 lymphopenia was reported in 8% of elotuzumab-treated patients. In clinical trials, laboratory abnormalities that worsened from baseline included lymphopenia (99%; grade 3 or 4, 77%), leukopenia (91%; grade 3 or 4, 32%), and thrombocytopenia (84%; grade 3 or 4, 19%) in patients who received elotuzumab, lenalidomide, and dexamethasone (n = 318) and lymphopenia (98%; grade 3 or 4, 70%), leukopenia (80%; grade 3 or 4, 52%), and thrombocytopenia (78%; grade 3 or 4, 17%) in patients who received elotuzumab, pomalidomide, and dexamethasone (n = 60).
Weight loss occurred in 14% of patients who received elotuzumab, lenalidomide, and dexamethasone (n = 318) compared with 6% of patients who received lenalidomide and dexamethasone alone (n = 317) for the treatment of relapsed or refractory multiple myeloma in a randomized, phase 3 trial; grade 3 and 4 weight loss was reported in 1.3% of elotuzumab-treated patients.
Cataracts occurred in 12% of patients who received elotuzumab, lenalidomide, and dexamethasone (n = 318) compared with 6% of patients who received lenalidomide and dexamethasone alone (n = 317) for the treatment of relapsed or refractory multiple myeloma in a randomized, phase 3 trial; grade 3 and 4 cataracts was reported in 6% of elotuzumab-treated patients.
Fatigue/asthenia occurred in 62% of patients who received elotuzumab, lenalidomide, and dexamethasone (n = 318) compared with 52% of patients who received lenalidomide and dexamethasone alone (n = 317) for the treatment of relapsed or refractory multiple myeloma in a randomized, phase 3 trial; grade 3 and 4 fatigue/asthenia was reported in 13% of elotuzumab-treated patients.
Fever occurred in 37% of patients who received elotuzumab, lenalidomide, and dexamethasone (n = 318) compared with 25% of patients who received lenalidomide and dexamethasone alone (n = 317) for the treatment of relapsed or refractory multiple myeloma in a randomized, phase 3 trial; grade 3 and 4 fever was reported in 2.5% of elotuzumab-treated patients.
Cough occurred in 34% of patients who received elotuzumab, lenalidomide, and dexamethasone (n = 318) compared with 19% of patients who received lenalidomide and dexamethasone alone (n = 317) for the treatment of relapsed or refractory multiple myeloma in a randomized, phase 3 trial; grade 3 and 4 cough was reported in 0.3% of elotuzumab-treated patients. Dyspnea occurred in 15% of patients who received elotuzumab, pomalidomide, and dexamethasone (n = 60) compared with 7% of patients who received pomalidomide and dexamethasone alone (n = 55) for the treatment of relapsed or refractory multiple myeloma in a randomized, phase 2 trial; grade 3 or 4 dyspnea was reported in 3.3% of elotuzumab-treated patients.
Headache occurred in 15% of patients who received elotuzumab, lenalidomide, and dexamethasone (n = 318) compared with 8% of patients who received lenalidomide and dexamethasone alone (n = 317) for the treatment of relapsed or refractory multiple myeloma in a randomized, phase 3 trial; grade 3 and 4 headache was reported in 0.3% of elotuzumab-treated patients.
Peripheral neuropathy (27% vs. 21%), extremity pain (16% vs. 10%), and oropharyngeal pain (10% vs. 4%) occurred more often with elotuzumab, lenalidomide, and dexamethasone (n = 318) compared with lenalidomide and dexamethasone alone (n = 317) in patients with relapsed or refractory multiple myeloma in a randomized, phase 3 trial; grade 3 and 4 peripheral neuropathy (3.8%) and extremity pain (0.9%) were also reported in elotuzumab-treated patients. Types of peripheral neuropathy reported in the clinical trial were axonal neuropathy, peripheral motor neuropathy, peripheral sensory neuropathy, and polyneuropathy. Hypoesthesia occurred in 5% or greater of patients who received elotuzumab in combination with lenalidomide and dexamethasone or pomalidomide and dexamethasone in clinical trials.
Hyperglycemia occurred in 20% of patients who received elotuzumab, pomalidomide, and dexamethasone (n = 60) compared with 15% of patients who received pomalidomide and dexamethasone alone (n = 55) for the treatment of relapsed or refractory multiple myeloma in a randomized, phase 2 trial; grade 3 or 4 hyperglycemia was reported in 8% of elotuzumab-treated patients. In clinical trials laboratory abnormalities that worsened from baseline included hyperglycemia (89%; grade 3 or 4, 17%), hyperkalemia (32%; grade 3 or 4, 7%), hypocalcemia (78%; grade 3 or 4, 11%) and metabolic acidosis/low bicarbonate level (63%; grade 3 or 4, 0.4%) in patients who received elotuzumab, lenalidomide, and dexamethasone (n = 318) and hyperglycemia (40%; grade 3 or 4, 3.3%), hyperkalemia (23%; grade 3 or 4, 5%), hypocalcemia (58%; grade 3 or 4, 3.3%), and hyponatremia (40%; grade 3 or 4, 5%) in patients who received elotuzumab, pomalidomide, and dexamethasone (n = 60).
Night sweats occurred in 5% or greater of patients with relapsed or refractory multiple myeloma who received elotuzumab in combination with lenalidomide and dexamethasone or pomalidomide and dexamethasone in clinical trials.
Chest pain (unspecified) occurred in 5% or greater of patients with relapsed or refractory multiple myeloma who received elotuzumab in combination with lenalidomide and dexamethasone or pomalidomide and dexamethasone in clinical trials.
Infusion-related reactions have been reported with elotuzumab therapy; most reactions occur during the first infusion. Observe patients during the elotuzumab infusion for signs and symptoms of infusion-related reactions (e.g., chest discomfort, fever, chills, hypertension or hypotension, and bradycardia); monitor vital signs every 30 minutes for 2 hours after the end of the infusion in patients who develop a reaction. Hold therapy and initiate appropriate medical support if a grade 2 or higher infusion-related reaction occurs; an infusion rate reduction or therapy discontinuation may be necessary depending on the severity of the reaction. Premedication with acetaminophen PO, an H1-blocker PO or IV (e.g., diphenhydramine), an H2-blocker PO or IV (e.g., ranitidine), and dexamethasone IV is required prior to each infusion. All patients should receive an additional oral dose of dexamethasone within 3 to 24 hours prior to every infusion. If dexamethasone is delayed or discontinued, consider the risk of a reaction versus the benefit of therapy when determining if a dose of elotuzumab should be administered. Infusion-related reactions were reported in 10% of relapsed or refractory multiple myeloma patients who received elotuzumab, lenalidomide, and dexamethasone (n = 318) in a randomized, phase 3 trial and 3.3% of relapsed or refractory multiple myeloma patients who received elotuzumab, pomalidomide, and dexamethasone (n = 60) in a randomized, phase 2 trial. Chest discomfort during the infusion was reported in 2% of patients who received elotuzumab, pomalidomide, and dexamethasone. Additionally, hypersensitivity occurred in 5% or greater of patients who received elotuzumab in these trials.
Antibody formation, evaluated using an electrochemiluminescent (ECL) assay, was observed in 18.5% of patients who received elotuzumab in pooled results from 4 clinical studies (n = 390); 88% of these patients developed antibodies within the first 2 months after starting elotuzumab and most antibodies disappeared within 2 to 4 months. Neutralizing antibodies developed in 6.4% of evaluable patients who received elotuzumab in this analysis. Additionally, antibody formation occurred in 36% of patients with multiple myeloma who received elotuzumab, pomalidomide, and dexamethasone in a randomized, phase 2 trial (n = 60); antibody formation occurred within the first 2 months of therapy and resolved within 2 to 3 months in most patients. Neutralizing antibodies developed in 3.8% of evaluable patients who received elotuzumab in this study.
Peripheral edema occurred in 13% of patients who received elotuzumab, pomalidomide, and dexamethasone (n = 60) compared with 7% of patients who received pomalidomide and dexamethasone alone (n = 55) for the treatment of relapsed or refractory multiple myeloma in a randomized, phase 2 trial.
Pulmonary embolism occurred in 3.1% of patients who received elotuzumab, lenalidomide, and dexamethasone (n = 318) compared with 2.5% of patients who received lenalidomide and dexamethasone alone (n = 317) for the treatment of relapsed or refractory multiple myeloma in a randomized, phase 3 trial.
Acute renal failure (unspecified) occurred in 2.5% of patients who received elotuzumab, lenalidomide, and dexamethasone (n = 318) compared with 1.9% of patients who received lenalidomide and dexamethasone alone (n = 317) for the treatment of relapsed or refractory multiple myeloma in a randomized, phase 3 trial.
Bone pain (15% vs. 9%) and muscle cramps/spasms (13% vs. 5%) occurred more often with elotuzumab, pomalidomide, and dexamethasone (n = 60) compared with pomalidomide and dexamethasone alone (n = 55) in patients with relapsed or refractory multiple myeloma in a randomized, phase 2 trial; grade 3 or 4 bone pain was reported in 3.3% of elotuzumab-treated patients.
Infusion-related reactions (e.g., chest discomfort, fever, chills, hypertension or hypotension, and bradycardia) have been reported with elotuzumab therapy; most infusion-related reactions occurred with the first infusion. Observe patients during the elotuzumab infusion for signs and symptoms of infusion-related reactions; monitor vital signs every 30 minutes for 2 hours after the end of the infusion in patients who develop a reaction. Hold therapy and initiate appropriate medical support if an infusion-related reaction occurs; an infusion rate reduction or therapy discontinuation may be necessary depending on the severity of the reaction. Premedication with acetaminophen PO, an H1-blocker PO or IV (e.g., diphenhydramine), an H2-blocker PO or IV (e.g., ranitidine), and dexamethasone IV is required prior to each infusion. All patients should receive an additional oral dose of dexamethasone within 3 to 24 hours prior to every infusion. If dexamethasone is delayed or discontinued, consider the risk of a reaction versus the benefit of therapy when determining if a dose of elotuzumab should be administered.
Infection (e.g., opportunistic, fungal, and viral infections) has been reported with elotuzumab therapy; some cases resulted in death. Monitor patients for signs and symptoms of infections; treat promptly if an infection develops.
New primary malignancy (e.g., solid tumors, hematologic malignancies, skin cancer) has been reported with elotuzumab therapy. Monitor patients for signs and symptoms of new primary malignancies.
Hepatotoxicity (e.g., elevated hepatic enzymes) has been reported with elotuzumab use. Monitor liver function tests periodically. Hold elotuzumab in patients who develop grade 3 or higher elevated hepatic enzymes during therapy. Consider restarting elotuzumab therapy when hepatic enzymes return to baseline values. No initial elotuzumab dosage adjustment appears necessary in patients with mild hepatic impairment. Use elotuzumab with caution in patients with moderate or severe hepatic disease; elotuzumab has not been studied in this patient population.
Elotuzumab can be detected on both the serum protein electrophoresis (SPEP) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This laboratory test interference may affect the determination of complete response or disease progression in some patients with IgG kappa myeloma protein. Especially in patients with an endogenous myeloma protein of IgA, IgM, IgD, or lambda light chain restricted, elotuzumab may cause a small peak in the early gamma region on SPEP that is IgG kappa on IFE.
The risk of fetal harm with elotuzumab use during pregnancy is unknown; elotuzumab has not been evaluated in pregnant women or in animal reproduction studies. Elotuzumab is given as part of a 3-drug combination regimen with lenalidomide and dexamethasone or pomalidomide and dexamethasone for the treatment of multiple myeloma; lenalidomide and pomalidomide may result in embryo-fetal harm and are contraindicated for use in pregnancy.
According to the manufacturer, breast-feeding is not recommended in women who are taking the 3-drug combination regimen of elotuzumab, lenalidomide, and dexamethasone or elotuzumab, pomalidomide, and dexamethasone due to a potential for serious adverse reactions in breast-fed infants. It is not known if elotuzumab is secreted in human milk or if it affects the breast-fed infant or milk production.
For the treatment of multiple myeloma:
NOTE: The FDA has designated elotuzumab as an orphan drug for the treatment of multiple myeloma.
-for the treatment of multiple myeloma in patients who have received 1 to 3 prior therapies, in combination with lenalidomide and dexamethasone:
Intravenous dosage:
Adults: 10 mg/kg IV once weekly on cycles 1 and 2 (on days 1, 8, 15, and 22), then every 2 weeks (on days 1 and 15) thereafter. Administer in combination with lenalidomide 25 mg orally daily on days 1 through 21 and dexamethasone 28 mg orally (taken 3 to 24 hours prior to elotuzumab) on days 1, 8, 15, and 22 on cycles 1 and 2 and on days 1 and 15 of subsequent cycles; give dexamethasone 40 mg orally on days 8 and 22 of cycles 3 and beyond. Repeat treatment cycles every 28 days until disease progression. Hold elotuzumab if a grade 2 or higher infusion-related reaction occurs; an infusion rate reduction or therapy discontinuation may be necessary depending on the severity of the reaction. Administer the following premedications 45 to 90 minutes prior to each elotuzumab infusion: acetaminophen 650 to 1,000 mg PO, diphenhydramine 25 to 50 mg PO or IV (or equivalent), an IV or oral H2-blocker, and dexamethasone 8 mg IV. At a median follow-up time of 24.5 months, the median progression-free survival time was significantly improved with elotuzumab plus lenalidomide and dexamethasone (median duration of therapy, 17 months) compared with lenalidomide and dexamethasone alone (19.4 months vs. 14.9 months; hazard ratio (HR) = 0.7; 95% CI, 0.57 to 0.85; p less than 0.001) in patients with relapsed and/or refractory multiple myeloma in a planned interim analysis of a multicenter, randomized, open-label, phase 3 trial (n = 646; the ELOQUENT-2 trial). In this study, patients had received a median of 2 prior therapies (range, 1 to 4 therapies); 35% of patients had refractory disease to the last therapy and 54% of patients had previously received an autologous stem cell transplantation. The overall survival time was improved in the elotuzumab-containing arm (48.3 months vs. 39.6 months; HR = 0.82; 95% CI, 0.68 to 1) at the final analysis (minimum follow-up time of 70.6 months). In subgroup analyses, the median OS times were significantly improved in elotuzumab-treated patients who had received 2 or 3 prior therapies (51 months vs. 33.6 months; HR = 0.71; 95% CI, 0.54 to 0.92), were refractory to their most recent therapy (40.4 months vs. 25.9 months; HR = 0.67; 95% CI, 0.49 to 0.91), or were less than 65 years of age (63.5 months vs. 47.7 months; HR = 0.7; 95% CI, 0.52 to 0.96).
-for the treatment of multiple myeloma in patients who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor, in combination with pomalidomide and dexamethasone:
Intravenous dosage:
Adults: 10 mg/kg IV once weekly on cycles 1 and 2 (on days 1, 8, 15, and 22), then give 20 mg/kg IV every 4 weeks (on day 1) starting on cycle 3. Administer elotuzumab in combination with pomalidomide 4 mg orally daily on days 1 through 21 and oral dexamethasone (age 75 years or less, 28 mg; age over 75 years, 8 mg) at 3 to 24 hours prior to elotuzumab on days 1, 8, 15, and 22 on cycles 1 and 2 and on day 1 of subsequent cycles. Additionally, give oral dexamethasone (age 75 years or less, 40 mg; age over 75 years, 20 mg) at 3 to 24 hours prior to elotuzumab on days 8, 15, and 22 of cycles 3 and beyond. Repeat treatment cycles every 28 days until disease progression. Hold elotuzumab if a grade 2 or higher infusion-related reaction occurs; an infusion rate reduction or therapy discontinuation may be necessary depending on the severity of the reaction. Administer the following premedications 45 to 90 minutes prior to each elotuzumab infusion: acetaminophen 650 to 1,000 mg PO, diphenhydramine 25 to 50 mg PO or IV (or equivalent), an IV or oral H2-blocker, and dexamethasone 8 mg IV. At a minimum follow-up time of 9.1 months, the median investigator-assessed progression-free survival time was significantly improved with elotuzumab plus pomalidomide and dexamethasone (median number of treatment cycles, 9) compared with pomalidomide and dexamethasone alone (10.3 months vs. 4.7 months; hazard ratio (HR) = 0.54; 95% CI, 0.34 to 0.86; p = 0.008) in patients with relapsed or refractory multiple myeloma in a multicenter, randomized, phase 2 trial (n = 117; the ELOQUENT-3 trial). In this study, patients had received a median of 3 (range, 2 to 8) prior therapies; 70% of patients had refractory disease after both lenalidomide and a proteasome inhibitor and 55% of patients had previously received a stem-cell transplantation. At a minimum follow-up time of 45 months, the median overall survival time was significantly improved in the elotuzumab arm (29.8 months vs. 17.41 months; HR = 0.59; 95% CI, 0.37 to 0.93).
Therapeutic Drug Monitoring:
Management of Treatment-Related Toxicity
NOTE: Refer to the lenalidomide and dexamethasone prescribing information for recommended dose delays and adjustments for these agents. The treatment with the other drugs in the regimen may continue as scheduled if one drug is held or discontinued.
Infusion-Related Reactions
Grade 2 or higher toxicity: stop the elotuzumab infusion until symptoms resolve to grade 1 or lower; resume the infusion at 0.5 mL/minute and increase the rate by 0.5 mL/minute every 30 minutes as tolerated until reaching the rate at which the infusion reaction occurred. If the patient does not experience any further reaction symptoms, continue to escalate the rate as tolerated (infusions 1 to 4, MAX rate of 2 mL/minute; subsequent infusions, MAX rate of 5 mL/minute). If the infusion reaction recurs, stop the infusion and do not restart the infusion that day. Severe infusion reactions may require permanent discontinuation.
Maximum Dosage Limits:
-Adults
20 mg/kg IV.
-Geriatric
20 mg/kg IV.
-Adolescents
Safety and efficacy not established.
-Children
Safety and efficacy not established.
-Infants
Safety and efficacy not established.
Patients with Hepatic Impairment Dosing
No elotuzumab dosage adjustment is necessary in patients with mild hepatic impairment based on data from a pharmacokinetic population analysis. Elotuzumab has not been studied in patients with moderate (total bilirubin level greater than 1.5- to 3-times the upper limit of normal (ULN) and any AST level) or severe (total bilirubin level greater than 3-times the ULN and any AST level) hepatic impairment. Hold elotuzumab in patients who develop grade 3 or higher elevated hepatic enzymes during therapy. Consider restarting elotuzumab therapy when hepatic enzymes return to baseline values.
Patients with Renal Impairment Dosing
No elotuzumab dosage adjustment is necessary in patients with renal impairment (creatinine clearance (CrCl) of 15 to 89 mL/min) or end-stage renal disease (CrCl less than 15 mL/min) with or without hemodialysis based on data from a pharmacokinetic population analysis.
*non-FDA-approved indication
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Elotuzumab is a humanized IgG1 monoclonal antibody that binds to the Signaling Lymphocytic Activation Molecule family member 7 (SLAMF7), a cell surface glycoprotein receptor, and interacts with Fc receptors on effector cells. It works by activating natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. SLAMF7 is highly expressed in multiple myeloma cells and is also expressed in mature NK cells. It appears that elotuzumab does not induce complement-dependent cytotoxicity. In preclinical models, synergistic cytotoxic effects in multiple myeloma cell lines and enhanced NK cell activation have been observed with the combination of elotuzumab and lenalidomide. In vivo, elotuzumab increased anti-tumor activity when used in combination with pomalidomide.
Elotuzumab is administered as an IV infusion. The pharmacokinetic (PK) parameters of elotuzumab were evaluated in 35 adult patients with previously treated advanced multiple myeloma in a phase I dose escalation study. In 4 patients that received elotuzumab 10 mg/kg, the mean Vd was 2.98 +/- 0.37 L, the mean clearance was 15.3 +/- 8.6 mL/hour, and the mean half-life was 4.6 +/- 0.1 days following the first dose. Based on a population PK models, about 97% of the maximum steady-state elotuzumab concentration is predicted to be eliminated at a geometric mean of 82.4 days (coefficient of variance (CV), 48%) when elotuzumab is administered in combination with lenalidomide and dexamethasone and at a geometric mean of 78 days (CV, 42%) when elotuzumab is administered in combination with pomalidomide and dexamethasone. When given in combination with lenalidomide and dexamethasone, elotuzumab clearance decreased from a geometric mean of 17.5 mL/day/kg (CV, 21.2%) to 5.8 mL/day/kg (CV, 31%) with increasing doses from 0.5 mg/kg to 20 mg/kg.
-Route-Specific Pharmacokinetics
Intravenous Route
Following the fourth dose of elotuzumab 10 mg/kg IV given every 2 weeks, the Cmax of 216.6 +/- 37.2 micrograms (mcg)/mL was achieved at a Tmax of 4.8 +/- 1.4 hours in a phase I dose escalation study in patients with advanced multiple myeloma; additionally, the AUCinf value was 27,220 mcg X hour/mL. Elotuzumab exhibits nonlinear pharmacokinetics (PK) demonstrated by greater than proportional increases in AUC values. Based on population PK models, the geometric mean steady-state trough concentration is about 194 mcg/mL (CV, 52%) when elotuzumab is administered in combination with lenalidomide and dexamethasone and about 124 mcg/mL (CV, 59%) when elotuzumab is administered in combination with pomalidomide and dexamethasone.
-Special Populations
Hepatic Impairment
Mild hepatic impairment did not clinically affect the pharmacokinetic parameters of elotuzumab in a population analysis. Elotuzumab has not been studied in patients with moderate or severe hepatic impairment.
Renal Impairment
Renal impairment (creatinine clearance (CrCl) of 15 to 89 mL/min) or end-stage renal disease (CrCl less than 15 mL/min) with or without hemodialysis did not clinically affect the pharmacokinetic parameters of elotuzumab in a population analysis.
Geriatric
Age (range, 37 to 88 years) did not clinically affect the pharmacokinetic (PK) parameters of elotuzumab in a population PK analysis.
Gender Differences
Gender did not clinically affect the pharmacokinetic (PK) parameters of elotuzumab in a population PK analysis.
Ethnic Differences
Race did not clinically affect the pharmacokinetic (PK) parameters of elotuzumab in a population PK analysis.
Obesity
Increased elotuzumab clearance correlates with increased body weight.
Other
Lactate Dehydrogenase (LDH) or Albumin levels
Baseline LDH or albumin concentrations did not clinically affect the pharmacokinetic (PK) parameters of elotuzumab in a population PK analysis.