Immunogenicity and Safety of a Third and Subsequent COVID-19 Vaccine Doses in Patients with Plasma Cell Dyscrasias

Plasma cell dyscrasias (PCD) are a group of hematological disorders associated with immune dysfunction from underlying disease and/or treatment. With continued circulation of 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 hematological malignancies. Participants were monitored longitudinally, and finger-prick dried blood spot (DBS) cards were obtained at specific intervals based on vaccination. Serum antibodies against SARS-CoV-2 proteins after the 3rd, 4th and 5th dose were measured by high-throughput ELISA. Differences in anti-spike 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 PCD participants with vaccine (anti-S) immunity compared to those with infection-derived (anti-N) immunity throughout the study. While vaccine responses appeared to wane 6 months after dose 3 and, to a lesser extent, dose 4, subsequent doses cumulatively increased anti-S immunity. Seropositivity decreased with anti-CD38 therapy and older age, although 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 PCD participants. While anti-CD38 therapy and age reduced seropositivity, antibody responses could still be enhanced with vaccine doses beyond the primary three-dose series.