My-DST distinguishes between resistance and sensitivity to the monoclonal antibody Dara. (A) Primary MM cells exhibit a dose-dependent reduction in viable MM cells after 48 hours ex vivo culture in the presence of Dara. (B) Waterfall plot of the ex vivo response to 20 nM Dara among newly diagnosed samples (blue bars) is similar to relapsed, Dara-naive patients (magenta bars), but Dara-exposed patients exhibited much less response (green bars). (C) The ex vivo sensitivity in Dara-naive samples was significantly better than samples from patients with prior exposure. (D) The CD38 expression levels were significantly higher in MM cells from samples scored as Dara sensitive than in MM cells that were scored as Dara resistant. (E) Ex vivo reduction of primary MM cells exposed to Dara correlated with the level of CD38 expression by flow cytometry. (F) The ex vivo daratumumab reduction in primary MM cells was largely reversed by macrophage deactivation with clodronate-containing liposomes (CL). Data represent means ± SD, comparisons by 2-tailed Student t test. *P < .05; **P < .01; ***P < .001. The blue line in panel E represents linear regression results, with the r and P values from Pearson’s correlations. Dx, diagnosis; MFI, median fluorescence intensity; NPC, nonplasma cells.