In late 2018, elotuzumab was approved for use in combination with pomalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.1
Supporting Efficacy Data
Approval was based on the findings of improved progression-free survival and overall response rate in the open-label phase II ELOQUENT-3 trial.1,2 In the trial, 117 patients were randomly assigned to receive elotuzumab with pomalidomide and low-dose dexamethasone (n = 60) or pomalidomide and low-dose dexamethasone (n = 57).
Treatment was administered in 4-week cycles until disease progression or unacceptable toxicity. Elotuzumab was given at 10 mg/kg each week for the first two cycles and 20 mg/kg every 4 weeks thereafter. Dexamethasone was administered prior to elotuzumab infusion.
The median number of prior therapies was three. Overall, 87% were refractory to lenalidomide; 80%, to a proteasome inhibitor; and 70%, to both lenalidomide and a proteasome inhibitor. Prior therapies included stem cell transplantation (55%), bortezomib (100%), lenalidomide (99%), cyclophosphamide (66%), melphalan (63%), carfilzomib (21%), and daratumumab (3%).
Minimum follow-up was 9 months. Median progression-free survival was 10.25 months in the elotuzumab group vs 4.67 months in the control group (hazard ratio = 0.54, P = .0078). Overall response rates were 53.3% vs 26.3% (P = .0029).
How It Works
Elotuzumab is a humanized IgG1 monoclonal antibody directed against signaling lymphocyte activation molecule family 7 (SLAMF7). SLAMF7 is present on myeloma cells independent of cytogenetic abnormalities and is also expressed on natural killer cells, plasma cells, and, at lower levels, on specific immune cell subsets of differentiated cells in the hematopoietic lineage.
Elotuzumab directly activates natural killer cells through both the SLAMF7 pathway and Fc receptors. It targets SLAMF7 on myeloma cells and facilitates interaction with natural killer cells to mediate killing of myeloma cells through antibody-dependent cellular cytotoxicity. In preclinical models, the combination of elotuzumab and lenalidomide resulted in natural killer cell activation greater than that with either alone and increased antitumor activity in vitro and in vivo.
How It Is Used
The recommended dosage of elotuzumab when given in combination with pomalidomide and low-dose dexamethasone is 10 mg/kg via intravenous (IV) infusion every week for the first two 28-day cycles. Starting at cycle 3, it is given at 20 mg/kg via IV infusion every 4 weeks. Product labeling provides specific instructions for the administration of elotuzumab in conjunction with pomalidomide and low-dose dexamethasone. Treatment should be continued until disease progression or unacceptable toxicity.
At 45 to 90 minutes prior to infusion, patients should receive premedication with the following: 8 mg of IV dexamethasone, an H1 blocker consisting of diphenhydramine (25 to 50 mg orally or IV) or an equivalent, an H2 blocker consisting of ranitidine (50 mg IV) or an equivalent, and acetaminophen (650 to 1,000 mg orally).
Product labeling provides detailed instructions on infusion rates for elotuzumab at 10 mg/kg and 20 mg/kg. For the 10-mg/kg dose, infusion is started at a rate of 0.5 mL/minute and can be increased in a stepwise fashion in the absence of an infusion reaction. The maximum infusion rate should not exceed 5 mL/min. For the 20-mg/kg dose, infusion should start at a rate of 3 mL/min and can be increased in stepwise fashion in the absence of an infusion reaction. The maximum infusion rate should not exceed 5 mL/min. Patients for whom administration has been escalated to 5 mL/min at the 10-mg/kg dose must have the rate decreased to 3 mL/min for the first infusion at 20 mg/kg.
If the dose of one drug in the regimen is delayed, interrupted, or discontinued, treatment with the other drugs may continue as scheduled. However, if dexamethasone is delayed or discontinued, the decision as to whether to administer elotuzumab should be based on clinical judgment regarding the risk of hypersensitivity.
For grade ≥ 2 infusion reactions, the infusion should be interrupted, and appropriate medical and supportive measures instituted. Upon resolution to grade ≤ 1, infusion can be restarted at 0.5 mL/min and gradually increased at a rate of 0.5 mL/min every 30 minutes as tolerated to the rate at which the infusion reaction occurred. The escalation regimen can be resumed if there is no recurrence of an infusion reaction.
In patients who experience an infusion reaction, vital signs should be monitored every 30 minutes for 2 hours after the end of infusion. If the infusion reaction recurs, infusion should be stopped and not restarted on that day. Severe infusion reactions may require permanent discontinuation of elotuzumab and emergency treatment.
In ELOQUENT-3, the most common adverse events of any grade occurring in ≥ 10% of the elotuzumab group and at an incidence ≥ 5% higher than in the pomalidomide/dexamethasone group included constipation (22% vs 11%), hyperglycemia (20% vs 15%), pneumonia (18% vs 13%), diarrhea (18% vs 9%), respiratory tract infection (17% vs 9%), bone pain (15% vs 9%), and dyspnea (15% vs 7%). The most common grade 3 or 4 adverse events included lymphopenia (8% vs 1.8%), bone pain (3.3% vs 0%), and dyspnea (3.3% vs 1.8%). The most common grade 3 or 4 laboratory abnormalities in the elotuzumab group were lymphopenia (70% vs 35%), leukopenia (52% vs 35%), and thrombocytopenia (17% vs 20%).
Serious adverse events occurred in 22% vs 15% of patients, with the most common in the elotuzumab group being pneumonia (13% vs 11%) and respiratory tract infection (7% vs 3.6%). Adverse events led to discontinuation of any component of study treatment in 5.0% vs 1.8%.
Elotuzumab carries warnings and precautions for infusion reactions, infections, second primary malignancies, hepatotoxicity, and interference with determination of complete response (through interference with assays used to monitor M-protein). Patients should be monitored for fever and other signs of infection. Patients should be monitored for liver function and treatment stopped if hepatotoxicity is suspected.
A higher incidence of second primary malignancies was observed in the elotuzumab group in the ELOQUENT-2 trial comparing elotuzumab plus lenalidomide vs lenalidomide in multiple myeloma (9% vs 6%). In ELOQUENT-3, second primary malignancy rates were 1.9% vs 0%.
Animal reproduction studies have not been conducted with elotuzumab. Elotuzumab is approved for use with lenalidomide and dexamethasone or pomalidomide and dexamethasone. Lenalidomide and pomalidomide can cause embryofetal harm and are contraindicated for use during pregnancy.
1. Empliciti (elotuzumab) for injection prescribing information, Bristol-Myers Squibb Company, November 2018. Available at www.emplicitihcp.com. Accessed November 11, 2019.
2. Dimopoulos MA, Dytfeld D, Grosicki S, et al: Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma. N Engl J Med 379:1811-1822, 2018.