Predicting COVID‐19 infection risk in lymphoma by immune monitoring

Abstract

Introduction: Patients with B-cell lymphoma have poorer antibody responses to COVID-19 vaccines compared to patients with other malignancies. However, the immune responses are heterogeneous and its association with clinical outcomes are poorly understood. Here, we study the association between antibody and cellular responses with the outcomes from COVID-19 infection from the PROSECO study. Methods: THE UK PROSECO study is a prospective observational cohort study evaluating COVID-19 vaccine response in people with lymphoma. Peripheral blood antibody titres (anti-spike (S) IgG by Mesoscale Discovery), antibody avidity (surface plasmon resonance) and IFNγ T-cell responses (ELISpot) against spike protein after two to four COVID-19 vaccines, and clinical outcomes data were collected. Results: 524 patients (92 Hodgkin lymphoma, 180 aggressive B non-Hodgkin lymphoma (B-NHL), 234 indolent B-NHL and 18 peripheral T-cell lymphoma) were included: 334 (84·3%), 315 (79·5%) and 266 (67·1%) participants were eligible for post-two, three and four vaccine dose analysis, respectively. Breakthrough infections (BTI) occurred in 20 (5.9%), 40 (12.7%) and 36 (13.5%) participants after two, three and four vaccine doses. Of 96 participants with BTI, 12 (12.5%) needed hospitalisation. No deaths were observed due to COVID-19 infection. No differences were observed in T-cell responses between BTI and non-BTI groups, but 4/9 (44.5%) hospitalised BTI cases had undetectable cellular and antibody responses. There was no association between antibody titres and infection episodes after two vaccine doses, but antibody titres were associated with lower BTI risk after three or four vaccine doses on multivariable analysis. Intriguingly, the antibody threshold associated with infection risk was lower after four than three vaccine doses (41 vs. 820 BAU/mL). We also observed stronger antibody binding avidity to SARS-CoV-2 spike receptor-binding domain (RBD) proteins from Wuhan and Omicron BQ.1 variants, with increasing vaccine doses, i.e., fourth versus third dose: 10-fold increase (p: <0.01); fourth versus second dose:100-fold-increase than the second dose (p: <0.0001) (see Figure). The research was funded by: the Blood Cancer UK Vaccine Research Collaborative, which is led by Blood Cancer UK in partnership with Myeloma UK, Anthony Nolan and the British Society for Haematology; a Cancer Research UK Advanced Clinician Scientist Fellowship to SH Lim; Cancer Research UK/National Institute for Health Research (NIHR) Southampton Experimental Cancer Medicine Center; NIHR Southampton Clinical Research Facility (Southampton Research Biorepository) and NIHR Southampton Biomedical Research Center; NIHR Great Ormond Street Biomedical Research Center and the NIHR Oxford Biomedical Research Center and CRUK Experimental Cancer Medicines Center. Keywords: Lymphoid Cancers, Other: Covid-19, Therapeutics and Clinical Trials in Lymphoma, vaccination Conflicts of interests pertinent to the abstract. M. Ahearne Research funding: Pfizer C. P. Fox Consultant or advisory role: Astra Zeneca G. P. Collins Consultant or advisory role: Astra Zeneca and Pfizer Research funding: Pfizer A. J. Davies Honoraria: Astra Zeneca and Janssen Research funding: Astra Zeneca and Janssen S. H. Lim Honoraria: Astra Zeneca