Humoral and cellular immune responses after three or four doses of BNT162b2 in patients with hematological malignancies
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Objectives: Initial responses to coronavirus disease 2019 vaccination are impaired in patients with hematological malignancies. We investigated immune responses after three or four doses of BNT162b2 in patients with myeloid and lymphoid malignancies compared to controls, and identified risk factors for humoral and cellular nonresponse 1 year after first vaccination. Methods: In 407 hematological patients (45 myeloid, 362 lymphoid) and 98 matched controls, we measured immunoglobulin G (IgG) and neutralizing antibodies specific for the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at baseline, 3 weeks, 2, 6, and 12 months, and interferon-γ release at 12 months. Results: In patients with lymphoid malignancies, SARS-CoV-2 receptor-binding domain IgG concentration and mean neutralizing capacity was lower than in controls at all time points. A diagnosis of chronic lymphocytic B-cell leukemia (CLL) or lymphoma was associated with humoral nonresponse at 12 months compared to having multiple myeloma/amyloidosis (p <.001 and p =.013). Compared to controls, patients with lymphoid malignancies had increased risk of cellular nonresponse. A lymphoma diagnosis was associated with lower risk of cellular nonresponse compared to patients with multiple myeloma/amyloidosis, while patients with CLL had comparable response rates to patients with multiple myeloma/amyloidosis (p =.037 and p =.280). Conclusions: In conclusion, long-term humoral and cellular immune responses to BNT162b2 were impaired in patients with lymphoid malignancies.
Originalsprog | Engelsk |
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Bogserie | European Journal of Haematology |
Vol/bind | 111 |
Udgave nummer | 2 |
Sider (fra-til) | 229-239 |
Antal sider | 11 |
ISSN | 0902-4441 |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
The authors would like to thank all patients and healthcare professionals who participated in the study. The authors also thank Mads Engelhardt Knudsen, Sif Kaas Nielsen, Bettina Eide Holm, Victoria Marie Linderod Larsen, and Emilie Caroline Skuladottir Bøgestad from the Laboratory of Molecular Medicine at Rigshospitalet, Betina Poulsen from the Blood Bank, Department of Clinical Immunology, Rigshospitalet, Lisbeth Andreasen, Annie Mørk, Fie Andreasen, Ann Kristine Thorsteinsson, Tung Thanh Phan, and Ida Stenroos‐Dam from the Department of Clinical Biochemistry and Annemette Hald from Department of Infectious Diseases at Rigshospitalet, for their excellent technical assistance in processing and analyzing the samples. Danish COVID‐19 Biobank (part of Bio‐ and Genome Bank Denmark) is acknowledged for biological material and for data regarding handling and storage. Line Dam Heftdal was funded by a grant from Rigshospitalets Research Committee. Kirsten Grønbæk is funded by a center grant from The Danish Cancer Society (Danish Research Center for Precision Medicine in Blood Cancer; grant 223‐A13071‐18‐S68), and from Greater Copenhagen Health Science Partners (Clinical Academic Group in Blood Cancers). This work was financially supported by grants from the Carlsberg Foundation (CF20‐4760045, granted to Peter Garred), the Novo Nordisk Foundation (NFF205A0063505 and NNF20SA0064201, granted to Peter Garred), and the Svend Andersen Research Foundation (SARF2021, granted to Peter Garred).
Funding Information:
Line Dam Heftdal, Laura Pérez‐Alós, Sebastian Rask Hamm, Johannes Roth Madsen, Jose Juan Almagro Armenteros, Kamille Fogh, Christoffer Cronwald Kronborg, Anders Pommer Vallentin, Rasmus Bo Hasselbalch, Dina Leth Møller, Cecilie Bo Hansen, Mia Pries‐Heje, Anne Ortved Gang, Sisse Rye Ostrowski, Ruth Frikke‐Schmidt, Erik Sørensen, Linda Hilsted, and Kasper Iversen declare no conflicts of interests. Henning Bundgaard has received lecture fees from Amgen, Sanofi‐Avensis, MSD, and BMS. Susanne Dam Nielsen has received unrestricted grants from The Novo Nordisk Foundation, Kirsten and Freddy Johannsen's Fund and Dr. Sofus Carl Emil Friis and Wife Olga Doris Friis Scholarship. Susanne Dam Nielsen has further received honoraria from Gilead and MSD and has served on advisory boards for Gilead, MSD, and GSK. Kirsten Grønbæk has received a research grant from Janssen Pharma and is on advisory boards for GSK and Nanexa.
Publisher Copyright:
© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.
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