ISB 1342 maintains high potency to kill tumor cells from patients previously treated with daratumumab. (A-C) Representative cytotoxicity curves of CD138⁺ MM cells by ISB 1342 and daratumumab at 18 to 24 hours in samples from patients not previously treated with daratumumab (dara-naïve, patient sample 4) (A), previously treated with daratumumab (dara-exposed, patient sample 15) (B), and dara-naïve plasma cell leukemia (PCL; patient sample 1) (C). Data are mean (A-B) or mean ± SEM of replicates (C) analyzed using nonlinear regression analysis. (D) Maximal cytotoxicity of CD138⁺ tumor cells with ISB 1342 (10-100 nM) or daratumumab (100 nM) in samples from dara-naïve patients (filled symbols) vs dara-exposed (open symbols). Dots represent individual samples, and data are mean ± SD compared using 1-way ANOVA followed by Dunnett multiple comparison analysis to daratumumab on dara-naïve samples. (E) Radar plot of average values for CD8⁺ T cells, NK cells, and monocytes/macrophages ratio to CD138⁺ MM cells in samples from dara-naïve patients (blue) vs dara-exposed ones (pink). (F) Representative CD8⁺ T-cell activation with ISB 1342 and isotype control measured by flow cytometry with expression of CD69 (blue) and CD25 (pink) in PCL. Data are mean ± SEM of replicates analyzed using nonlinear regression analysis. (G) Maximum T-cell activation (CD25 and CD69) and degranulation (CD107a) on dara-naïve vs dara-exposed patient samples with ISB 1342. Data are mean ± SD compared using unpaired t test.