Vaccine Efficacy after Rituximab Exposure: First Interim Analysis of Virtue Project on Behalf of West Midlands Research Consortium, UK

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.196-196
• Main Authors: Shields, Adrian M, Venkatachalam, Srinivasan, Paneesha, Shankara, Ford, Mark, Sheeran, Tom, Kelly, Melanie, Karim, Farheen, Qureshi, Iman, Salhan, Beena, DeSilva, Neelakshi, Stones, Jacqueline, Lee, Sophie, Khawaja, Jahanzeb, Kaudlay, Praveen Kumar, Whitmill, Richard, Nabikakepoto, Ghulam, Faustini, Sian E, Richter, Alex G, Drayson, Mark T, Basu, Supratik
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-150220

▪ Background: Anti-CD20 B cell depleting agents are amongst the most commonly used immunotherapeutics employed in the treatment of haematological malignancy and autoimmune diseases. By inducing peripheral B cell aplasia, anti-CD20 depleting agents are hypothesised to significantly impair serological responses to neoantigens, including the SARS-CoV-2 spike glycoprotein within SARS-CoV-2 vaccines. Seropositivity following SARS-CoV-2 is the strongest, measurable correlate of protection from severe COVID-19. Understanding the kinetics of B cell reconstitution and vaccine responsiveness following exposure to B cell depleting agents is essential to maximise vaccine efficacy in patients vulnerable to severe COVID-19. Methods: 80 patients with underlying haematological malignancy and 38 patients with underlying rheumatological disease previously treated with anti-CD20 B cell depleting agents were studied following their second dose of a SARS-CoV-2 vaccine (median time to sampling: 46.5d, IQR: 33.8-63.3). Lymphocyte subset (CD4, CD8, CD19, CD56/16) enumeration was performed using 6 colour flow cytometry (BD Trucount). Total anti-SARS-CoV-2 spike glycoprotein antibodies were measured by enzyme-linked immunosorbent assay (The Binding Site, Human Anti-IgG/A/M SARS-CoV-2-ELISA). The relationship between immune reconstitution following B cell depletion and vaccine responsiveness was explored. Results: In the haematology cohort (median age 70y, IQR 60.3-76.0, 62.5% male), overall seropositivity following vaccination was 60.0%. Individuals on active chemotherapy had significantly lower seroprevalence than those vaccinated following the completion of chemotherapy (22.7% vs 74.1%, p