Combination of forimtamig with SoC agents. (A-D) Total BM cells from 4 (carfi) or 11 (dara and pom) patients with NDMM were cultured in the presence of 1 nM forimtamig, 10 nM daratumumab, 1 μM pomalidomide (48 hours before incubation), 3 nM carfilzomib, or combination of forimtamig with either of the SoC agents for 48 hours, and tumor cell lysis as well as expression of CD69, CD25, CD137, and PD-1 by CD8⁺ lymphocytes was measured by flow cytometry; tumor cell lysis was calculated by the percentage reduction of CD38⁺CD138⁺ double-positive cells in relation to untreated TCB control; and graphs summarizing the mean ± SEM expression and statistical differences against forimtamig monotherapy were determined by 1-way ANOVA with Tukey posttest analysis. ∗P < .05; ∗∗P < .005; ∗∗∗P < .0005; ∗∗∗∗P < .0001. (E-G)Humanized NSG (huNSG) mice were subcutaneously implanted with NCI-H929 tumor cells and when tumors reached 200 mm³ injected once weekly with 0.1 mg/kg forimtamig or combination of forimtamig with 8 mg/kg dara (once weekly, IV), 10 mg/kg pomalidomide (every day, by mouth [po]), or 3 mg/kg carfi (twice weekly, IV). Tumor volume was measured over time using a caliper; treatment was stopped after 6 cycles and mice were monitored for at least 2 additional weeks to check for tumor relapse; each group includes 10 animals and is presented as mean + SEM. (H-J) Serum was harvested from n = 5 animals 48 hours after first forimtamig and 24 hours after first SoC dosing and cytokine levels were measured by bioplex analysis; graphs summarizing the mean ± SEM expression and statistical differences between multiple groups were determined by1e-way ANOVA with Tukey posttest analysis. ∗P < .05; ∗∗P < .005; ∗∗∗P < .0005; ∗∗∗∗P < .0001. hu, human; TNF-α, tumor necrosis factor α.