T-cell response after 2 doses of SARS-CoV-2 vaccination. (A) Receptor-binding domain (RBD)-specific spot-forming units (SFUs) per 3 × 10⁵ peripheral blood mononuclear cells (PMBCs) stratified for healthy controls (Ctrl) vs patients with MM for quantification of IFN-γ-mediated T-cell response. (B) S2-specific SFUs and (C) CEF/CEFT-specific SFUs per 3 × 10⁵ PBMCs stratified for Ctrls vs patients with MM. SFUs in the negative control were subtracted from all RBD, S2, and CEF/CEFT-peptide treated conditions to normalize for unspecific IFN-γ secretion. Dashed horizontal lines indicate cutoff, determined by ROC analysis for T-cell response (D). The graph shows the tests sensitivity plotted against the specificity (100% − proportion of false positives) measured by the IFN-γ response of healthy individuals before and after SARS-CoV-2 vaccination (T1 and T3) upon stimulation with S2 and RBD peptides (area = 0.7767; 95% confidence interval, 0.6431-0.9121, P = .002). We selected a cutoff value of 55 SFU per 3 × 10⁵ PBMCs because this value still yields a specificity >95% (95.5%), whereas the sensitivity is >50% (53.8%). (E) Representative images of IFN-γ ELISpot from patients with MM who did or did not respond in comparison with a healthy control who responded to the vaccination. (F) Spearman correlation matrix for levels of serologic response, T-cell response, and prevaccination immune cell status. The color axis corresponds to the Spearman correlation coefficient for each correlation. P values are reported as *<.05, **<0.01, ***<.001. (G) Multivariate logistic regression analysis for factors affecting achievement of T-cell response with numeric report of the odds ratio (OR) and P values <.05 are indicated with *.