ELOQUENT-3: Adding Elotuzumab to Pomalidomide, Dexamethasone Improves PFS in R/R Multiple Myeloma

David Bai, PharmD

ELOQUENT-3 trial results found that adding elotuzumab to pomalidomide and dexamethasone improved progression-free survival (PFS) and overall response rate (ORR) in patients with multiple myeloma that had relapsed from or were refractory to (R/R) lenalidomide and a proteasome inhibitor.

Immunomodulatory agents and proteasome inhibitors are the mainstay for treatment of multiple myeloma. Once patients relapse or become refractory, prognosis becomes extremely poor, with overall survival averaging 9 months. The triplet regimen of elotuzumab in combination with lenalidomide and dexamethasone, which combines an immunomodulatory agent with elotuzumab in patients with multiple myeloma who have progressed after at least 1 previous therapy, was approved in 2015.

Elotuzumab is a humanized monoclonal antibody that binds to signaling lymphocytic activation molecule F7 (SLAMF7) on the surface of myeloma cells and natural killer cells to initiate natural killer cell–mediated cellular cytotoxicity or macrophage-mediated killing on myeloma cells. Because pomalidomide also affects the immune system, investigators said that a combination of elotuzumab and pomalidomide will work synergistically and enhance cell-mediated killing of myeloma cells. In the phase 2 ELOQUENT-3 study, the efficacy and safety of elotuzumab plus pomalidomide and dexamethasone are compared with pomalidomide and dexamethasone in patients with refractory or R/R multiple myeloma who already received lenalidomide and a proteasome inhibitor.

Patients who were refractory or R/R to lenalidomide and a proteasome inhibitor were randomized in a 1:1 ratio to receive either elotuzumab plus pomalidomide and dexamethasone (elotuzumab group) or pomalidomide and dexamethasone (control group). Median PFS was 10.3 months in the elotuzumab group compared with 4.7 months in the control group (hazard ratio, 0.54, 95% CI, 0.34-0.86; P = .008). The addition of elotuzumab was beneficial across all key patient subgroups, including patients who received at least 4 previous lines of therapy and patients with at least one cytogenetic abnormalities (eg chromosome 17p deletion). ORR was also higher in the elotuzumab group (53%) than the control group (26%), with 20% of patients in the elotuzumab group having a very good partial response or better compared with 9% in the control group. Median duration of response was not reached in the elotuzumab group and 8.3 months in the control group.

Reported AEs were similar between the 2 groups. The most common grade 3 or 4 adverse events (AEs) in the elotuzumab and control group, respectively, were neutropenia (13% vs 27%), anemia (10% vs 20%), infections (13% vs 22%), and hyperglycemia (8% vs 7%). AEs that led to discontinuation occurred in 18% of the patients in the elotuzumab group compared with 24% of the patients in the control group.
Elotuzumab in combination with pomalidomide and dexamethasone is shown to be effective and safe and can be considered for patients who progressed after lenalidomide and a proteasome inhibitor.

Dimopoulos MA, Dytfeld D, Grosicki S, et al. Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma. N Engl J Med. 2018;379(19):1811-1822. doi: 10.1056/NEJMoa1805762.
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