Co-incubation with daratumumab (DARA) or pomalidomide (POM) enhances talquetamab-mediated lysis. (A) BM-MNCs obtained from 8 NDMM, 11 daratumumab-naïve RRMM. and 6 daratumumab-refractory RRMM patients were incubated for 48 hours with serial dilutions of talquetamab (0.00128-0.8 µg/mL) with or without daratumumab 0.1 µg/mL. Surviving MM cells were enumerated using flow cytometry. (B) The effect of talquetamab with or without daratumumab on the frequency of CD38⁺ T cells, CD38⁺ CD4⁺ T cells, and CD38⁺ CD8⁺ T cells was assessed by flow cytometric analysis. (C) The impact of talquetamab with or without daratumumab on T-cell lysis, T-cell activation (CD25 positivity), and T-cell degranulation (CD107a positivity) was determined by flow cytometry. (D) For pomalidomide experiments, BM-MNCs obtained from 5 NDMM, 1 RRMM, and 7 DARA-R MM patients were incubated for 48 hours with serial dilutions of talquetamab (0.00128-4.0 µg/mL) with or without pomalidomide (2 µM). MM cell lysis was assessed by flow cytometry. (E) T-cell lysis, T-cell activation (CD25 positivity) and T-cell degranulation (CD107a positivity) were measured by flow cytometry. (F) Granzyme B concentration was measured in the cell-culture supernatants of BM-MNCs, obtained from 5 patients, treated for 48 hours with serial dilutions of talquetamab (0.00128-0.8 µg/mL) with or without pomalidomide (2 µM). Granzyme B concentrations are depicted as fold change compared with solvent control. (B-C,E-F) Results of talquetamab monotherapy were compared with combinatorial treatment by nonlinear regression analysis with matched 2-way ANOVA and Sidak’s posttest. (A-F) Data are depicted as mean ± SEM of individual experiments, performed in duplicate. *P < .05; **P < .01; ***P < .001; ****P < .0001.