Predicting COVID‐19 infection risk in lymphoma by immune monitoring.
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Authors
Wijaya, R.
Campbell, N.
Johnson, M.
Stuart, B.
Kelly, A.
Tipler, N.
Coleman, A.
Turaj, A.
Menne, T.
Ahearne, M.
Issue Date
2023-06
Type
Published Abstract
Language
Keywords
Research Subject Categories::MEDICINE::Dermatology and venerology,clinical genetics, internal medicine::Internal medicine::Lung diseases , Research Subject Categories::MEDICINE::Surgery::Oncology
Alternative Title
Abstract
ntroduction: 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 re sponses 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 vac cine 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 re sponses between BTI and non‐BTI groups, but 4/9 (44.5%) hospital ised BTI cases had undetectable cellular and antibody responses.
There was no association between antibody titres and infection ep isodes 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 infec tion 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).
Conclusion: Anti‐S antibody titres can predict the risk of COVID‐19
infection after three or more vaccine doses in patients with lym phoma. Repeated COVID‐19 vaccination drives antibody affinity
maturation and consequently improves the strength of antibody
binding to virus spike proteins. Nearly half of participants who
required hospitalisation for COVID‐19 had undetectable antibody
and cellular immunity to vaccination. Altogether, these data show the
importance of booster vaccine doses and immune monitoring post
COVID‐19 vaccination to identify lymphoma patients who still
continue to be at risk from severe COVID‐19, and thus the best
prophylactic and therapeutic strategies.
606 - SUPPLEMENT ABSTRACTS
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 Haematol ogy; a Cancer Research UK Advanced Clinician Scientist Fellowship
to SH Lim; Cancer Research UK/National Institute for Health
Research (NIHR) Southampton Experimental Cancer Medicine Cen ter; 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.
Description
Citation
Wijaya R, Campbell N, Johnson M, et al. Predicting COVID‐19 infection risk in lymphoma by immune monitoring. Hematological Oncology. 2023;41:606-607. doi:10.1002/hon.3164_456