SEROLOGICAL RESPONSES AFTER SARS‐COV‐2 VACCINATION FIRST DOSE IN PATIENTS WITH LYMPHOID MALIGNANCY: FIRST INTERIM ANALYSIS OF THE UK PROSECO STUDY

Abstract

Introduction: A population-wide SARS-CoV-2 vaccination programme commenced in the UK in December 2020. Two vaccines have been widely deployed; BNT162b2 (Pfizer) and a ChAdOx1 nCoV-19 (Astra Zeneca) both encoding the full length of the spike (S) protein. The vaccines are administered in two doses 12 weeks apart, as opposed to 3-weekly in other countries. Studies in healthy individuals indicate that a single dose of the vaccine induces detectable anti-S IgG antibodies in most adults. Patients with lymphoid malignancies risk more severe COVID-19 and are also likely to be poor vaccine responders. PROSECO is a prospective observational study to evaluate the robustness and persistence of SARS-CoV-2 vaccine responses, and identify baseline clinical parameters correlated to vaccine responses. Methods: Patients with a confirmed lymphoma diagnosis undergo blood sampling prior to vaccination, 4 weeks after the first dose, and 2-4 weeks, 6 and 12 months after the second dose. IgG to SARS-CoV-2 Spike, Receptor Binding Domain (RBD) and nucleocapsid protein are tested using a qualified electrochemiluminescent assay (Meso-Scale Discovery®) calibrated to the WHO International reference serum (NIBSC 20/136) and compared to responses in healthy volunteers. T-cell reactivity against spike protein will be assessed by ELISpot. Results: This first interim analysis reports the serological response of 44 participants with lymphoma (6 Hodgkin lymphoma, 12 diffuse large B cell lymphoma, 16 follicular lymphoma, 2 mantle cell lymphoma, 2 chronic lymphocytic leukaemia, 2 marginal zone lymphoma, 4 peripheral T-cell lymphoma), and data from 49 healthy volunteers analysed on the same platform, 4 weeks after their first dose of vaccination. Post-vaccination anti-S IgG levels were significantly lower in patients with lymphoma (geometric mean 3.4 U/ml) compared to healthy participants (geometric mean 331.3 U/ml (Pfizer) and 66.5 U/ml (Astra Zeneca)). Among patients vaccinated during systemic anti-lymphoma therapy, only 2/26 had anti-S IgG >10 Units/ml, compared to 11/18 patients who have had no treatment, or who completed therapy >6 months before the first vaccination dose. In the post-treatment group, patients with curable disease (n = 5) had anti-S IgG levels comparable to healthy participants. In contrast, the serological response in incurable indolent lymphomas, 4/8 cases exhibiting poor responses despite never being treated or completed treatment >3 years previously. Conclusions: This initial analysis indicates that patients with lymphoma receiving treatment have a reduced serological response (14-fold vs untreated) to the first dose of SARS-CoV-2 vaccination and suggests a rationale for prompt administration of the second dose. Patients with indolent lymphoma showed persistently poor serological responses irrespective of treatment and might benefit from further vaccine boosters.