SAR442085 displays a better antitumor activity than daratumumab and isatuximab in vivo. (A-D) HuCD38-EL-4 cell line was injected IV into huFcgR mice that were treated with SAR442085, daratumumab, or isatuximab (IP; 10 mg/kg [B] or 1.25 mg/kg [C]). Isotype control was used at 10 mg/kg, and the same group is represented in panels B and C. (A) Experimental design. (B-C) Kaplan-Meier survival curves showing the survival of mice after treatment with the indicated mAbs at 10 mg/kg (B) or 1.25 mg/kg (C). Statistical analyses were performed using log-rank tests and after Bonferonni Holm correction. **: P < .01 vs control group; ns = non-significant vs control; ^##: P < .01 vs daratumumab; x: P < .05 vs isatuximab. (D) The percentages of the indicated splenic immune cell populations were determined for the indicated groups of mice. Data are pooled from 10 mg/kg and 1.25 mg/kg mAb treated mice. Statistical analyses were performed using Kruskal-Wallis test followed by Dunn’s tests for pairwise comparisons. P values < 0.05 were considered statistically significant. *: P < .05; ***: P < .001; ns = non-significant. (E-G) Purified NK cell from huFcgR mice were injected into Rag2^−/−IL2rg^−/− mice. Seven days after mice were challenged with Vk12653-huCD38 cells (2 × 10⁶; IV) and subsequently treated as specified with 1 mg/Kg of SAR442085, daratumumab, isatuximab, or isotype. (E) Experimental design. (F-G) Representative picture (F) and Graph (G) of serum protein electrophoresis 35 days post-MM challenge. Statistical analyses were performed using Kruskal-Wallis test followed by Dunn’s tests for pairwise comparisons. *P < .05; **P < .01, ***P < .001. (H) Kaplan-Meier curves showing the evolution of paraproteinemia-free mice for the indicated groups of mice. n = 22-24 mice pooled from 5 independent experiments. Statistical analyses were performed using log-rank tests followed by a Holm-Sidak correction for multiplicity. **P < .01, ***P < .001