Efficacy of SARS-CoV-2 vaccination in patients with monoclonal gammopathies: A cross sectional study

Abstract

SARS-CoV-2 vaccination is the most effective strategy to protect individuals with haematologic malignancies against severe COVID-19, while eliciting limited vaccine responses. We characterized the humoral responses following 3 mo after mRNA-based vaccines in individuals at different plasma-cell disease stages: monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma on first-line therapy (MM), compared with a healthy population. Plasma samples from uninfected MM patients showed lower SARS-CoV-2-specific antibody levels and neutralization capacity compared with MGUS, SMM, and healthy individuals. Importantly, COVID-19 recovered MM individuals presented significantly higher plasma neutralization capacity compared with their uninfected counterparts, highlighting that hybrid immunity elicit stronger immunity even in this immunocompromised population. No differences in the vaccine-induced humoral responses were observed between uninfected MGUS, SMM and healthy individuals. In conclusion, MGUS and SMM patients could be SARS-CoV-2 vaccinated following the vaccine recommendations for the general population, whereas a tailored monitoring of the vaccine-induced immune responses should be considered in uninfected MM patients.

Figure S1.. Flowchart of VAC-COV-GM HMAR study, including 59 patients with monoclonal gammopathies.

Figure 1.. Comparison of humoral response between uninfected and infected individuals suffering from monoclonal gammopathies compared with a control group (CG).

(A, B, C) Levels of specific SARS-CoV-2 immunoglobulins IgG (Panel A), IgA (Panel B), and IgM (Panel C) against S2+RBD proteins quantified in plasma from uninfected and infected participants by ELISA after 3 mo from SARS-CoV-2 vaccination. Panel (D) Neutralizing activity against WH1 virus after 3 mo of vaccine administration in infected and uninfected participants. Dotted line indicates the 25^th percentile of neutralization titer from CG. In all panels, median values are indicated and P-values were obtained from Mann–Whitney test for comparison between groups. Each symbol represents a participant, and are color-coding according to their disease group (MGUS, purple square; SMM, upper triangle turquoise; MM, lower triangle orange; and CG, blue diamond). Source data are available for this figure.

Figure 2.. Comparison of humoral response after 3 mo from mRNA vaccination in uninfected patients with monoclonal gammopathies compared with a control group (CG).

(A, B, C, D) Levels of specific SARS-CoV-2 immunoglobulins IgG (Panel A), IgA (Panel B), and IgM (Panel C) against S2+RBD proteins quantified and neutralizing activity against WH1 (Panel D) from MGUS, SMM, and MM patients and a control group (CG) after 3 mo of vaccine administration. (D) Dotted line indicates the 25^th percentile of neutralization titer from CG (Panel D). Panel (E) Ratio of plasma neutralization titer per total SARS-CoV-2 IgG antibodies. Median values are indicated; P-values were obtained from Kruskal–Wallis test for comparison between groups and the post hoc Dunn’s multiple comparison’s test. Only significant P-values are shown. Each symbol represents a participant, and are color-coding according to their disease group (MGUS, purple square; SMM, upper triangle turquoise; MM, lower triangle orange, and CG, blue diamond). Source data are available for this figure.

Figure S2.. Humoral responses in MM patients according to treatment.

(A, B) MM patients were sub-grouped according to their Daratumumab treatment to evaluate SARS-CoV-2–specific IgG antibody levels (Panel A) and neutralization capacity (Panel B). (C, D) In addition, MM patients were sub-grouped if they underwent autologous hematopoietic stem cell transplantation (auto-HSCT), to evaluate the impact in the SARS-CoV-2–specific IgG antibodies levels (Panel C) and neutralization capacity (Panel D). For all panels, median values are indicated and P-values were obtained from Mann–Whitney test for comparison between groups. For panels (B) and (D), dotted line indicates the 25th percentile of neutralization titer from CG.

Figure 3.. Correlations between variables.

Panel (A) Correlation matrix of relevant continuous variables including MGUS, SMM, MM, and CG participants. Spearman coefficients are indicated in the lower part of the panel, whereas P-values in the upper part. Only significant correlations are plotted (P < 0.05). Positive correlations are shown in blue, whereas negative in red. (B, C) Detail of the correlation between the levels of SARS-CoV-2–specific IgG (Panel B) and IgA (Panel C) antibodies and neutralization capacity. Each symbol represents a participant, and are color-coding according to their disease group (MGUS, purple square; SMM, upper triangle turquoise; MM, lower triangle orange, and CG, blue diamond). Correlation coefficient and P-values were obtained from Spearman correlation.