Empliciti (elotuzumab) is a humanized monoclonal antibody used in combination with Revlimid (lenalidomide) and dexamethasone, and in combination with Pomalyst (pomalidomide) and dexamethasone for the treatment of relapsed and refractory multiple myeloma (RRMM) patients who have undergone two or three previous therapies. Empliciti is an intravenous injection marketed by Bristol Myers Squibb.
How does Empliciti work?
The signaling lymphocytic activation molecule F7 (SLAMF7, also called CS1) is a glycoprotein receptor found at high levels on the surface of myeloma cells, natural killer (NK) cells, and other immune cells. Empliciti specifically targets SLAMF7 molecules and works in two ways: It binds to SLAMF7 on myeloma cells and renders them vulnerable to recognition and killing by NK cells, and it activates NK cells and other immune cells that produce SLAMF7.
Empliciti in clinical trials
Results of a multicenter, open-label, dose-escalation Phase 1 clinical trial were reported in the journal Blood. A total of 35 RRMM patients received up to six doses (0.5, 1, 2.5, 5, 10, or 20 mg/kg) of Empliciti by intravenous (into-the-vein) infusion once every 14 days for eight weeks. Patients who did not show evidence of relapse at eight weeks had the option to receive a second eight-week treatment course. After completion of the treatment, patients were evaluated for adverse events 30 days and 60 days after the last dose. Empliciti was well tolerated, and the adverse events reported were mild to moderate and mostly linked to the infusion. They included cough, headache, back pain, fever, and chills.
A Phase 1 study (NCT00742560) evaluated the safety and efficacy of a combined treatment of Empliciti, Revlimid, and dexamethasone in 28 RRMM patients who had been treated with two or three prior therapies. Three patients received 5 mg/kg, three patients received 10 mg/kg, and 22 patients received 20 mg/kg of Empliciti intravenously on days one, eight, 15, and 22 of a 28-day cycle in the first two cycles, and on days one and 15 in the subsequent cycles. All patients also received 25 mg of oral Revlimid on days one to 21, and 40 mg oral dexamethasone once a week. The primary outcome measures included the percentage of patients with dose-limiting toxicities during the first cycle and the percentage of patients showing clinical responses during each cycle.
Study results, reported in the Journal of Clinical Oncology, showed that the triple-combination therapy was well tolerated, and no dose-limiting toxicities were observed. The most frequent adverse events included low neutrophil and platelet counts. Two patients experienced serious infusion reactions during the first treatment cycle. Of the 28 patients, 23 (82%) had objective responses. Patients treated with 20 mg/Kg of Empliciti did not show disease progression until a median of 16.4 months.
A randomized, multicenter, open-label, dose-escalation Phase 2 trial (NCT00742560) was conducted at 17 hospitals in the U.S., Canada, France, and Germany. Some 73 RRMM patients who had previously received one to three therapies were randomly assigned to either 10 mg/kg or 20 mg/kg of intravenous Empliciti, plus 25 mg of oral Revlimid and 40 mg of dexamethasone. Empliciti was given on days one, eight, 15, and 22 in the first cycle and on days one and 15 in subsequent cycles. Revlimid was given on days one to 21, and dexamethasone was given once per week. The treatment was carried out in 28-day cycles until disease progression was observed. The primary measure was objective response.
Results of the study, reported in the journal Lancet Hematology, showed that the safety of the combination therapy was acceptable. The efficacy was better than previously noted with the combination of Revlimid and dexamethasone. At data cutoff (nearly four years after the start of treatment), 13 of 79 patients remained on the treatment. A total of 33 patients in the 10 mg/kg group and 28 patients in the 20 mg/kg group achieved an objective response. The most common treatment-related adverse events included diarrhea, muscle spasms, and fatigue. The most common severe, or grade 3, adverse events included lymphopenia and neutropenia.
A randomized, open-label Phase 3 trial (NCT01239797) called ELOQUENT-2 investigated whether the addition of Empliciti to a combination of Revlimid and dexamethasone would improve progression-free survival (PFS) — the length of time a person lives without disease worsening — in RRMM patients. For the trial, 321 patients were randomly assigned to the Empliciti group (Empliciti plus Revlimid and dexamethasone) and 325 patients to the control group (Revlimid plus dexamethasone). The primary objectives were PFS and the overall response rate (ORR).
Interim results, reported in the New England Journal of Medicine, showed that RRMM patients who received a combination of the three treatments had a relative reduction of 30% in the risk of disease progression or death compared with the group who received the dual-combo therapy. Median PFS was 19.4 months in the first group, and 14.9 months in the second group. The ORR was 79% in the first group, compared with 66% in the control group. The most common severe or life-threatening (grade 3 or 4) adverse events were lymphopenia, neutropenia, fatigue, and pneumonia. Infusion reactions occurred in 33 patients in the Empliciti group, but these were mostly mild or moderate (grade 1 or 2).
Extended four-year follow-up results, reported in the journal Cancer, were similar to those reported at two or three years. The Empliciti group showed a 29% lower risk of disease progression or death compared with the control group, and long-term safety was maintained. The relative PFS benefit for Empliciti-treated patients was more than 50 months.
A randomized, open-label, Phase 2 trial (NCT02654132) called ELOQUENT-3 investigated whether adding Empliciti to a combination of Pomalist and dexamethasone was more effective in extending PFS compared with Pomalyst and dexamethasone alone. A total of 60 patients were randomly assigned to the first group, and 57 patients were assigned to the second group.
Results of this study, reported in the New England Journal of Medicine, found that the median PFS was 10.3 months in the Empliciti group, compared with 4.7 months in the control group. The ORR was 53% in the Empliciti group and 26% in the control group. The most common grade 3 or 4 adverse events were neutropenia, anemia, and hyperglycemia. At least 65% of the patients in each group had infections, and infusion reactions were reported in three patients in the Empliciti group.
The U.S. Food and Drug Administration approved Empliciti for the treatment of RRMM patients in combination with Revlimid and dexamethasone in November 2015 based on the results of the ELOQUENT-2 trial, and in combination with Pomalyst and dexamethasone in November 2018 based on the results of the ELOQUENT-3 trial.
Last updated: Jan. 9, 2020
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