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Safety and immunogenicity of one versus two doses of the COVID-19 vaccine BNT162b2 for patients with cancer: interim analysis of a prospective observational study

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Leticia Monin, Adam G Laing, Miguel Muñoz-Ruiz, Duncan R McKenzie, Irene Del Molino Del Barrio, Thanussuyah Alaguthurai, Clara Domingo-Vila, Thomas S Hayday, Carl Graham, Jeffrey Seow, Sultan Abdul-Jawad, Shraddha Kamdar, Elizabeth Harvey-Jones, Rosalind Graham, Jack Cooper, Muhammad Khan, Jennifer Vidler, Helen Kakkassery, Shubhankar Sinha, Richard Davis & 24 more Liane Dupont, Isaac Francos Quijorna, Charlotte O'Brien-Gore, Puay Ling Lee, Josephine Eum, Maria Conde Poole, Magdalene Joseph, Daniel Davies, Yin Wu, Angela Swampillai, Bernard V North, Ana Montes, Mark Harries, Anne Rigg, James Spicer, Michael H Malim, Paul Fields, Piers Patten, Francesca Di Rosa, Sophie Papa, Timothy Tree, Katie J Doores, Adrian C Hayday, Sheeba Irshad

Original languageEnglish
Pages (from-to)765-778
Number of pages14
JournalThe Lancet Oncology
Volume22
Issue number6
Early online date27 Apr 2021
DOIs
E-pub ahead of print27 Apr 2021
PublishedJun 2021

Bibliographical note

Funding Information: The SOAP study (IRAS 282337) is sponsored by King's College London and Guy's and St Thomas' Foundation NHS Trust. The study is funded by grants from the King's College London Charity funds to SI (PS10822), and from Cancer Research UK to SI (C56773 / A24869), programme grants from Breast Cancer Now including SI at King's College London and to the Breast Cancer Now Toby Robin's Research Center at the Institute of Cancer Research, London, UK. This work was also supported by the Wellcome Trust Investigator Award to ACH (grant number 106292/Z/14/Z) and MHM (grant number 106223/Z/14/Z); the Rosetrees and John Black Charitable Foundation award to ACH (grant number 11130); the Cancer Research UK Cancer Immunotherapy Accelerator, and a UK COVID-Immunology-Consortium grant to AH (grant number C33499/A20265); the King's Together Rapid COVID-19 Call awards to KJD, MHM, and ACH; the Foundation Dormeur, Vaduz for funding equipment to KJD; the Huo Family Foundation Award to MHM and KJD; the Cancer Research Institute Irvington Fellowship (DRM); the MRC-KCL Doctoral Training Partnership in Biomedical Sciences (CG; grant number MR/N013700/1); and the Francis Crick Institute (ACH), which receives core funding from Cancer Research UK (grant number FC001093), the Medical Research Council (grant number FC001093), and the Wellcome Trust (grant number FC001093). We thank patients and blood donors who consented to participate in this study and the medical and research teams at the Guy's and St Thomas' Trust hospitals. We thank members of the Guy's and St Thomas' Trust and King's College Hospital trial teams who contributed to patient recruitment for the SOAP study at these hospitals; and clinical colleagues at King's College Hospital, King's College Hospital, and the Princess Royal University Hospital for assisting with patient identification and sample collection. Funding Information: The SOAP study (IRAS 282337) is sponsored by King's College London and Guy's and St Thomas' Foundation NHS Trust. The study is funded by grants from the King's College London Charity funds to SI (PS10822), and from Cancer Research UK to SI (C56773 / A24869), programme grants from Breast Cancer Now including SI at King's College London and to the Breast Cancer Now Toby Robin's Research Center at the Institute of Cancer Research, London, UK. This work was also supported by the Wellcome Trust Investigator Award to ACH (grant number 106292/Z/14/Z) and MHM (grant number 106223/Z/14/Z); the Rosetrees and John Black Charitable Foundation award to ACH (grant number 11130); the Cancer Research UK Cancer Immunotherapy Accelerator, and a UK COVID-Immunology-Consortium grant to AH (grant number C33499/A20265); the King's Together Rapid COVID-19 Call awards to KJD, MHM, and ACH; the Foundation Dormeur, Vaduz for funding equipment to KJD; the Huo Family Foundation Award to MHM and KJD; the Cancer Research Institute Irvington Fellowship (DRM); the MRC-KCL Doctoral Training Partnership in Biomedical Sciences (CG; grant number MR/N013700/1); and the Francis Crick Institute (ACH), which receives core funding from Cancer Research UK (grant number FC001093), the Medical Research Council (grant number FC001093), and the Wellcome Trust (grant number FC001093). We thank patients and blood donors who consented to participate in this study and the medical and research teams at the Guy's and St Thomas' Trust hospitals. We thank members of the Guy's and St Thomas' Trust and King's College Hospital trial teams who contributed to patient recruitment for the SOAP study at these hospitals; and clinical colleagues at King's College Hospital, King's College Hospital, and the Princess Royal University Hospital for assisting with patient identification and sample collection. Publisher Copyright: © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

BACKGROUND: The efficacy and safety profiles of vaccines against SARS-CoV-2 in patients with cancer is unknown. We aimed to assess the safety and immunogenicity of the BNT162b2 (Pfizer-BioNTech) vaccine in patients with cancer.

METHODS: For this prospective observational study, we recruited patients with cancer and healthy controls (mostly health-care workers) from three London hospitals between Dec 8, 2020, and Feb 18, 2021. Participants who were vaccinated between Dec 8 and Dec 29, 2020, received two 30 μg doses of BNT162b2 administered intramuscularly 21 days apart; patients vaccinated after this date received only one 30 μg dose with a planned follow-up boost at 12 weeks. Blood samples were taken before vaccination and at 3 weeks and 5 weeks after the first vaccination. Where possible, serial nasopharyngeal real-time RT-PCR (rRT-PCR) swab tests were done every 10 days or in cases of symptomatic COVID-19. The coprimary endpoints were seroconversion to SARS-CoV-2 spike (S) protein in patients with cancer following the first vaccination with the BNT162b2 vaccine and the effect of vaccine boosting after 21 days on seroconversion. All participants with available data were included in the safety and immunogenicity analyses. Ongoing follow-up is underway for further blood sampling after the delayed (12-week) vaccine boost. This study is registered with the NHS Health Research Authority and Health and Care Research Wales (REC ID 20/HRA/2031).

FINDINGS: 151 patients with cancer (95 patients with solid cancer and 56 patients with haematological cancer) and 54 healthy controls were enrolled. For this interim data analysis of the safety and immunogenicity of vaccinated patients with cancer, samples and data obtained up to March 19, 2021, were analysed. After exclusion of 17 patients who had been exposed to SARS-CoV-2 (detected by either antibody seroconversion or a positive rRT-PCR COVID-19 swab test) from the immunogenicity analysis, the proportion of positive anti-S IgG titres at approximately 21 days following a single vaccine inoculum across the three cohorts were 32 (94%; 95% CI 81-98) of 34 healthy controls; 21 (38%; 26-51) of 56 patients with solid cancer, and eight (18%; 10-32) of 44 patients with haematological cancer. 16 healthy controls, 25 patients with solid cancer, and six patients with haematological cancer received a second dose on day 21. Of the patients with available blood samples 2 weeks following a 21-day vaccine boost, and excluding 17 participants with evidence of previous natural SARS-CoV-2 exposure, 18 (95%; 95% CI 75-99) of 19 patients with solid cancer, 12 (100%; 76-100) of 12 healthy controls, and three (60%; 23-88) of five patients with haematological cancers were seropositive, compared with ten (30%; 17-47) of 33, 18 (86%; 65-95) of 21, and four (11%; 4-25) of 36, respectively, who did not receive a boost. The vaccine was well tolerated; no toxicities were reported in 75 (54%) of 140 patients with cancer following the first dose of BNT162b2, and in 22 (71%) of 31 patients with cancer following the second dose. Similarly, no toxicities were reported in 15 (38%) of 40 healthy controls after the first dose and in five (31%) of 16 after the second dose. Injection-site pain within 7 days following the first dose was the most commonly reported local reaction (23 [35%] of 65 patients with cancer; 12 [48%] of 25 healthy controls). No vaccine-related deaths were reported.

INTERPRETATION: In patients with cancer, one dose of the BNT162b2 vaccine yields poor efficacy. Immunogenicity increased significantly in patients with solid cancer within 2 weeks of a vaccine boost at day 21 after the first dose. These data support prioritisation of patients with cancer for an early (day 21) second dose of the BNT162b2 vaccine.

FUNDING: King's College London, Cancer Research UK, Wellcome Trust, Rosetrees Trust, and Francis Crick Institute.

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