Talquetamab-mediated lysis of primary MM cells. BM-MNCs obtained from 13 NDMM, 17 daratumumab-naïve RRMM, and 15 daratumumab-refractory RRMM patients were incubated with solvent control, serial dilutions of talquetamab (0.00128-4.0 µg/mL), and control antibodies (4.0 µg/mL) for 48 hours, after which surviving CD138⁺ MM cells (A), as well as T and NK cells (B), were enumerated using flow cytometric analysis. Lysis (y-axis) of MM cells (red), T cells (orange) and NK cells (gray) is depicted in the graphs. Negative lysis values indicate that cell numbers are higher when compared with solvent control. (C) Talquetamab-mediated tumor cell lysis in samples obtained from NDMM (lime green), daratumumab-naïve RRMM (light blue), and daratumumab-refractory RRMM (magenta) patients was compared using nonlinear regression analysis. EC₅₀ values are provided for each patient category. (D) Talquetamab-mediated activation and degranulation of CD4⁺ T cells, CD8⁺ T cells, and NK cells were assessed after a 48-hour culture in all 45 patient samples by flow cytometric analysis of CD25 and CD107a cell surface expression, respectively. Data represent mean ± SEM; experiments performed in duplicate. Representative flow cytometry histogram overlays depict cell surface expression of CD25 (green) and CD107a (purple) on CD4⁺ and CD8⁺ T cells treated with talquetamab (4.0 µg/mL) for 48 hours, compared with solvent control (gray). (E) T-cell activation and T-cell degranulation were also assessed per patient category (NDMM [lime green], daratumumab-naïve RRMM [light blue], and daratumumab-refractory RRMM [magenta]), and compared using nonlinear regression analysis. (F) Granzyme B and cytokines were measured in the cell-culture supernatants of BM-MNCs treated with solvent control or talquetamab for 48 hours. BM-MNCs were obtained from 5 daratumumab-naïve RRMM and 1 daratumumab-refractory RRMM patient. Data are depicted as different symbols, representing the mean of 4 measurements per patient, with box and whiskers, representing median values, 25th-75th percentile, and range. Data were normalized to solvent control. GZMB, granzyme B.