Figure 2 Expression of... | American Society of Hematology

Figure 2

$Figure 2. Expression of complement-inhibitory proteins and susceptibility to daratumumab-mediated CDC. (A) Susceptibility of 33 MM and lymphoma cell lines toward daratumumab-mediated CDC according to expression levels of CD38, CD46, CD55, and CD59 as determined by flow cytometry. Daratumumab induced CDC in 6 of 33 cell lines (white bars), whereas the others were completely resistant (black bars). Shown are mean ± SEM of 6 experiments. (B) Expression levels of CD38, CD55, and CD59 on 14 MM and lymphoma cell lines, after incubation with solvent control (white bar) or phospholipase-C (black bar) for 30 minutes. Shown are mean ± SEM. P values between the indicated groups were calculated using paired Student t tests. (C) CDC assays were performed with the same 14 cell lines as shown in B, which were pretreated with phospholipase-C (black bars) or solvent control (white bars) for 30 minutes. CDC assays were performed with 10 μg/mL daratumumab or IgG1-b12 control antibody as described in Materials and methods. Shown are mean ± SEM of 3 experiments. P values between the indicated groups were calculated using a paired Student t test; *P < .05, **P < .01, ***P < .001, ns, not significant. (D) Positive correlation between CD38 expression levels on primary MM cells and CDC mediated by 10 μg/mL daratumumab at 1 hour (n = 32 MM patients). No significant correlation between CD55, CD59, and CD46 expression levels on primary MM cells and CDC mediated by 10 μg/mL daratumumab at 1 hour (n = 32 MM patients). Expression levels were determined by flow cytometry. CDC assays were performed as described in Materials and methods. Correlations between variables were analyzed using the Spearman’s rank correlation coefficient. (E) CD46, CD55, and CD59 expression levels were analyzed by flow cytometry in 102 BM samples obtained from relapsed/refractory MM patients before start of treatment with daratumumab monotherapy at a dose of 16 mg/kg in the GEN501 and SIRIUS studies. Shown are median, 25th-75th percentile (box), and minimum and maximum value (whiskers). CD46, CD55, and CD59 expression levels on MM cells were compared between responders (defined as PR or better) and nonresponders. P values between the indicated groups were calculated using the Mann-Whitney U test. Every dot represents a patient.$

Expression of complement-inhibitory proteins and susceptibility to daratumumab-mediated CDC. (A) Susceptibility of 33 MM and lymphoma cell lines toward daratumumab-mediated CDC according to expression levels of CD38, CD46, CD55, and CD59 as determined by flow cytometry. Daratumumab induced CDC in 6 of 33 cell lines (white bars), whereas the others were completely resistant (black bars). Shown are mean ± SEM of 6 experiments. (B) Expression levels of CD38, CD55, and CD59 on 14 MM and lymphoma cell lines, after incubation with solvent control (white bar) or phospholipase-C (black bar) for 30 minutes. Shown are mean ± SEM. P values between the indicated groups were calculated using paired Student t tests. (C) CDC assays were performed with the same 14 cell lines as shown in B, which were pretreated with phospholipase-C (black bars) or solvent control (white bars) for 30 minutes. CDC assays were performed with 10 μg/mL daratumumab or IgG1-b12 control antibody as described in Materials and methods. Shown are mean ± SEM of 3 experiments. P values between the indicated groups were calculated using a paired Student t test; *P < .05, **P < .01, ***P < .001, ns, not significant. (D) Positive correlation between CD38 expression levels on primary MM cells and CDC mediated by 10 μg/mL daratumumab at 1 hour (n = 32 MM patients). No significant correlation between CD55, CD59, and CD46 expression levels on primary MM cells and CDC mediated by 10 μg/mL daratumumab at 1 hour (n = 32 MM patients). Expression levels were determined by flow cytometry. CDC assays were performed as described in Materials and methods. Correlations between variables were analyzed using the Spearman’s rank correlation coefficient. (E) CD46, CD55, and CD59 expression levels were analyzed by flow cytometry in 102 BM samples obtained from relapsed/refractory MM patients before start of treatment with daratumumab monotherapy at a dose of 16 mg/kg in the GEN501 and SIRIUS studies. Shown are median, 25th-75th percentile (box), and minimum and maximum value (whiskers). CD46, CD55, and CD59 expression levels on MM cells were compared between responders (defined as PR or better) and nonresponders. P values between the indicated groups were calculated using the Mann-Whitney U test. Every dot represents a patient.

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