Immunogenicity and safety of a third and subsequent COVID-19 vaccine doses in patients with plasma cell dyscrasias

ABSTRACT: Plasma cell dyscrasias (PCD) are a group of hematologic disorders associated with immune dysfunction from underlying disease and/or treatment. With the continued circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), optimizing and maintaining durable protection in this vulnerable population through vaccination remains important. A prospective cohort study was conducted between August 2021 and January 2023 across 12 sites in Canada to evaluate humoral immunity to COVID-19 vaccination in participants with hematologic malignancies. Participants were monitored longitudinally, and finger-prick dried blood spot cards were obtained at specific intervals based on vaccination. Serum antibodies against SARS-CoV-2 proteins after the third, fourth, and fifth dose were measured by high-throughput enzyme-linked immunosorbent assay. Differences in antispike (anti-S) seropositivity by vaccine dose number and clinical risk factors were analyzed by logistic regression. A total of 262 unique participants with 983 samples were included for analysis, among which 66% were diagnosed with PCD. Analysis of the predicted probability of immunity showed consistently higher proportions of participants with PCD with vaccine (anti-S) immunity compared with those with infection-derived (antinucleocapsid) immunity throughout the study. Although vaccine responses appeared to wane 6 months after dose 3 and, to a lesser extent, after dose 4, subsequent doses cumulatively increased anti-S immunity. Seropositivity decreased with anti-CD38 therapy and older age, although the receipt of additional vaccine doses significantly improved anti-S immunity. Overall, this study demonstrated that the third and subsequent COVID-19 vaccine doses could safely improve humoral immunity in participants with PCD. Although anti-CD38 therapy and age reduced seropositivity, antibody responses could still be enhanced with vaccine doses beyond the primary 3-dose series.