Impaired booster-induced SARS-CoV-2 antibody responses in rituximab-treated B-cell lymphoma patients despite peripheral B-cell recovery

Abstract

Background. Rituximab-treated patients with B-cell lymphoma exhibit profound B-cell depletion and impaired vaccine-induced antibody responses. However, it remains uncertain whether recovery of peripheral B-cell counts after rituximab is sufficient to restore effective humoral immunity following booster vaccination.

Patients and methods. In this prospective, single-centre observational study at the Institute of Oncology Ljubljana, adult B-cell lymphoma patients treated with or previously exposed to rituximab received the Comirnaty® mRNA COVID-19 vaccine. Antibody responses to the SARS-CoV-2 spike and nucleoprotein were measured at baseline, 14 days after the second dose, and at 3, 6, 9, and 12 months. A third dose was given at 6 months. T-cell responses (IFN-γ release) were assessed in patients before and after the primary series and booster dose. Lymphocyte subsets were analysed pre-vaccination. Adverse events and nutritional status were monitored.

Results. Patients undergoing anti-CD20 therapy showed absent antibody responses. Longer intervals since rituximab correlated with peripheral B-cell repopulation. However, even after reaching normal B-cell counts, patients’ antibody responses after revaccination remained significantly lower than in controls.

Conclusion. Rituximab is associated with impaired vaccine-induced antibody responses. Despite recovery of peripheral B-cell counts, patients with B-cell lymphoma show reduced humoral responses compared with healthy individuals following booster COVID-19 vaccination.