Elotuzumab induces NK cell activation in PBMC/myeloma cell coculture in vitro and in patients with MM when combined with lenalidomide and dexamethasone. (A-B) PBMCs from healthy donors were incubated alone or with OPM-2 cells for 4 hours (A) or 20 hours (B) in the presence of either hIgG1 or increasing doses of elotuzumab (Elo). Surface expression of CD107a, CD69, and CD54 and intracellular levels of IFN-γ and TNF-α were determined by using flow cytometry with gating on live CD56^dimCD3⁻ lymphocytes. Results are representative of at least 4 donors. (C) Culture supernatant was collected at 20 hours, and NK-secreted IFN-γ, TNF-α, MIP-1α, and MIP-1β levels were measured by CBA. Data are presented as fold change comparing the cytokine levels in the presence of elotuzumab with those obtained in the presence of hIgG1. Differences were assessed by using a Student t test. (D-E) Analysis of bone marrow samples taken at time of screening (SCRN, gray box) and at C1D22 (red box) in patients with RRMM treated with ELd. (D) Median fluorescence intensity (MFI) of CD54 on CD56^dimCD16⁺CD3⁻ cells; n = 44 (P < .01). (E) Percentage of plasma cells (CD45^dimCD138⁺) from bone marrow; n = 44 (P = .026). *P < .05; **P < .01; ***P < .001.