Longitudinal SARS-CoV-2 mRNA Vaccine-Induced Humoral Immune Responses in Patients with Cancer

Abstract

Longitudinal studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced immune responses in patients with cancer are needed to optimize clinical care. In a prospective cohort study of 366 (291 vaccinated) patients, we measured antibody levels [anti-spike (IgG-(S-RBD) and anti-nucleocapsid immunoglobulin] at three time points. Antibody level trajectories and frequency of breakthrough infections were evaluated by tumor type and timing of treatment relative to vaccination. IgG-(S-RBD) at peak response (median = 42 days after dose 2) was higher (P = 0.002) and remained higher after 4 to 6 months (P = 0.003) in patients receiving mRNA-1273 compared with BNT162b2. Patients with solid tumors attained higher peak levels (P = 0.001) and sustained levels after 4 to 6 months (P < 0.001) compared with those with hematologic malignancies. B-cell targeted treatment reduced peak (P = 0.001) and sustained antibody responses (P = 0.003). Solid tumor patients receiving immune checkpoint inhibitors before vaccination had lower sustained antibody levels than those who received treatment after vaccination (P = 0.043). Two (0.69%) vaccinated and one (1.9%) unvaccinated patient had severe COVID-19 illness during follow-up. Our study shows variation in sustained antibody responses across cancer populations receiving various therapeutic modalities, with important implications for vaccine booster timing and patient selection. SIGNIFICANCE: Long-term studies of immunogenicity of SARS-CoV-2 vaccines in patients with cancer are needed to inform evidence-based guidelines for booster vaccinations and to tailor sequence and timing of vaccinations to elicit improved humoral responses.

Figure 1.

Trajectories of IgG (S-RBD) antibody levels after two-dose mRNA vaccination among cancer patients. Blue, data for patients with solid tumors; green, for patients with hematologic malignancies; red, for the referent population (HCW). Dotted red lines represent the minimal cutoff for seroconversion defined as IgG(S-RBD) = 50 AU/mL and correlate of neutralization [IgG(S-RBD) = 4,160 AU/mL].

Figure 2.

Post-vaccination IgG(S-RBD) antibody levels at peak and sustained time points among cancer patients by vaccine type: BNT162b2 vs. mRNA-1273 (A); tumor type: solid tumor vs. hematologic malignancy (B); treatment among individuals with B-cell malignancies: B-cell targeted vs. no B-cell targeted (C); and treatment among individuals with solid tumors: ICI, ICI + chemotherapy, chemotherapy vs. other (D). Dots in box plots depict IgG(S-RBD) antibody levels; boxes represent the first quartile, median, and third quartile; whiskers represent minimum and maximum values. Stacked bar chart denote seropositivity (high, solid blue; intermediate, light blue; none, white). Dotted red lines represent the minimal cutoff for seroconversion [IgG(S-RBD) = 50 AU/mL] and correlate of neutralization [IgG(S-RBD) = 4,160 AU/mL].

Figure 3.

Post-vaccination IgG(S-RBD) antibody levels at peak and sustained time points among patients with solid tumors treated with immune checkpoint inhibitors by timing of vaccination administration. Dots in box plots depict IgG(S-RBD) antibody levels; boxes represent the first quartile, median, and third quartile; whiskers represent minimum and maximum values. Stacked bar chart denote seropositivity (high, solid blue; intermediate, light blue; none, white). Dotted red lines represent the minimal cutoff for seroconversion [IgG(S-RBD) = 50 AU/mL] and correlate of neutralization [IgG(S-RBD) = 4,160 AU/mL].