Safety and Immunogenicity of the BNT162b2 mRNA COVID-19 Vaccine in Patients after Allogeneic HCT or CD19-based CART therapy-A Single-Center Prospective Cohort Study

Abstract

Data are scarce regarding both the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing immune cell therapy; thus, we prospectively evaluated these two domains in patients receiving this vaccine after allogeneic hematopoietic cell transplantation (HCT; n = 66) or after CD19-based chimeric antigen receptor T cell (CART) therapy (n = 14). Overall, the vaccine was well tolerated, with mild non-hematologic vaccine-reported adverse events in a minority of the patients. Twelve percent of the patients after the first dose and 10% of the patients after the second dose developed cytopenia, and there were three cases of graft-versus-host disease exacerbation after each dose. A single case of impending graft rejection was summarized as possibly related. Evaluation of immunogenicity showed that 57% of patients after CART infusion and 75% patients after allogeneic HCT had evidence of humoral and/or cellular response to the vaccine. The Cox regression model indicated that longer time from infusion of cells, female sex, and higher CD19⁺ cells were associated with a positive humoral response, whereas a higher CD4⁺/CD8⁺ ratio was correlated with a positive cellular response, as confirmed by the ELISpot test. We conclude that the BNT162b2 mRNA COVID-19 vaccine has impressive immunogenicity in patients after allogeneic HCT or CART. Adverse events were mostly mild and transient, but some significant hematologic events were observed; hence, patients should be closely monitored.

Keywords: CART; COVID-19; HCT; Vaccination.

Figure 1

Intracellular cytokine staining. (A) Representative flow cytometry plots of convalescent stimulated peripheral blood mononuclear cells (PBMCs). Cells were stimulated overnight with the indicated peptide pools in the presence of brefeldin A. The following day, cells were fixed, permeabilized, and intracellularly stained for IL-2 and IFN-γ. Left columns show results of gated CD4s and right columns of gated CD8s. As can be seen, stimulation with pooled M peptides resulted in the highest IL-2 and IFN-γ staining in CD4⁺ cells, but the S peptide pool resulted in lower levels of secretion, which were even lower for the N peptide pool. Of note, CD8⁺ cells were negative for the stained cytokines, which could theoretically suggest that the peptide pools used preferentially bind to major histocompatibility complex II. (B) Bar graph showing the average percent of cytokine-positive cells within CD4⁺ T cells after stimulation of PBMCs with different mixed peptide pools (N, S, or M). The average of five convalescent donors is shown. Stimulation with the M peptide pool led to a significantly higher percent of IL-2⁺ and IFN-γ⁺ cells.

Figure 2

Disposition of patients.

Figure 3

Adverse events of vaccine.

Figure 4

(A) Skin rash consistent with dermal vasculitis after the first vaccine dose. (B) Hb, ANC, PLT, and percentage of donor chimerism in a patient with impending secondary graft rejection. Hb indicates hemoglobin; ANC, absolute neutrophil count; PLT, platelets; DLI indicates donor lymphocyte infusion.

Figure 5

Box plot of serology blood levels in patients after allogeneic HCT and after CART infusion.