Immune response to COVID-19 vaccination is attenuated by poor disease control and antimyeloma therapy with vaccine driven divergent T-cell response

Karthik Ramasamy; Ross Sadler; Sally Jeans; Paul Weeden; Sherin Varghese; Alison Turner; Jemma Larham; Nathanael Gray; Oluremi Carty; Joe Barrett; Stella Bowcock; Udo Oppermann; Gordon Cook; Chara Kyriakou; Mark Drayson; Supratik Basu; Sally Moore; Sarah McDonald; Sarah Gooding; Muhammad K Javaid

doi:10.1111/bjh.18066

Immune response to COVID-19 vaccination is attenuated by poor disease control and antimyeloma therapy with vaccine driven divergent T-cell response

Br J Haematol. 2022 May;197(3):293-301. doi: 10.1111/bjh.18066. Epub 2022 Feb 17.

Authors

Karthik Ramasamy¹, Ross Sadler², Sally Jeans³, Paul Weeden³, Sherin Varghese⁴, Alison Turner⁵, Jemma Larham⁶, Nathanael Gray⁵, Oluremi Carty², Joe Barrett⁵, Stella Bowcock⁷, Udo Oppermann⁵, Gordon Cook⁸, Chara Kyriakou⁹, Mark Drayson¹⁰, Supratik Basu¹¹, Sally Moore¹², Sarah McDonald¹³, Sarah Gooding^{14

15}, Muhammad K Javaid⁵

Affiliations

¹ Oxford University Hospitals NHS Trust, Radcliffe Department of Medicine, Oxford University, Oxford, UK.
² Department of Immunology, Churchill Hospital, Oxford University Hospitals NHS, Foundation Trust, Oxford, UK.
³ The Botnar Research Centre, Headington, UK.
⁴ Late Phase Haematology, Oxford University Hospital NHS Foundation Trust, Churchill Hospital, Oxford, UK.
⁵ Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
⁶ Oxford University Hospitals NHS Trust, Oxford, UK.
⁷ Princess Royal University Hospital, King's College Hospital Foundation NHS Trust, Kent, UK.
⁸ NIHR Leeds Medtech & In vitro Diagnostics Cooperative, Leeds Teaching Hospitals Trust, Leeds, UK.
⁹ Department of Haematology, University College London Hospitals NHS Trust, London, UK.
¹⁰ College of Medical and Dental Sciences Medical School, University of Birmingham, Birmingham, UK.
¹¹ University of Wolverhampton, The Royal Wolverhampton NHS Trust, Wolverhampton, UK.
¹² Oxford University Hospitals NHS Trust, NHS Foundation Trust, Oxford and Bath Royal United Hospitals, Bath, UK.
¹³ Myeloma UK, Beaverbank Business Park, Edinburgh, UK.
¹⁴ MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
¹⁵ Department of Haematology, Oxford University Hospitals NHS Trust, Oxford, UK.

Abstract

Myeloma patients frequently respond poorly to bacterial and viral vaccination. A few studies have reported poor humoral immune responses in myeloma patients to COVID-19 vaccination. Using a prospective study of myeloma patients in the UK Rudy study cohort, we assessed humoral and interferon gamma release assay (IGRA) cellular immune responses to COVID-19 vaccination post second COVID-19 vaccine administration. We report data from 214 adults with myeloma (n = 204) or smouldering myeloma (n = 10) who provided blood samples at least three weeks after second vaccine dose. Positive Anti-spike antibody levels (> 50 iu/ml) were detected in 189/203 (92.7%), positive IGRA responses were seen in 97/158 (61.4%) myeloma patients. Only 10/158 (6.3%) patients were identified to have both a negative IGRA and negative anti-spike protein antibody response. In all, 95/158 (60.1%) patients produced positive results for both anti-spike protein serology and IGRA. After adjusting for disease severity and myeloma therapy, poor humoral immune response was predicted by male gender. Predictors of poor IGRA included anti-CD38/anti-BCMA (B-cell maturation antigen) therapy and Pfizer-BioNTech vaccination. Further work is required to understand the clinical significance of divergent cellular response to vaccination.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antibodies, Viral
BNT162 Vaccine
COVID-19 Vaccines
COVID-19* / prevention & control
Humans
Immunity, Humoral
Male
Multiple Myeloma* / therapy
Prospective Studies
SARS-CoV-2
T-Lymphocytes
Vaccination

Substances

Antibodies, Viral
COVID-19 Vaccines
BNT162 Vaccine