Antibody Response in Immunocompromised Patients With Hematologic Cancers Who Received a 3-Dose mRNA-1273 Vaccination Schedule for COVID-19.

Autor:	Haggenburg S; Department of Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.; Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Amsterdam, the Netherlands., Hofsink Q; Department of Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.; Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Amsterdam, the Netherlands., Lissenberg-Witte BI; Department of Epidemiology and Data Science, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands., Broers AEC; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., van Doesum JA; Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., van Binnendijk RS; Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, Bilthoven, the Netherlands., den Hartog G; Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, Bilthoven, the Netherlands., Bhoekhan MS; Department of Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.; Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Amsterdam, the Netherlands., Haverkate NJE; Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Amsterdam, the Netherlands.; Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Burger JA; Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Bouhuijs JH; Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Smits GP; Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, Bilthoven, the Netherlands., Wouters D; Central Diagnostic Laboratory, Amsterdam UMC, Amsterdam, the Netherlands., van Leeuwen EMM; Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Amsterdam, the Netherlands.; Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Bontkes HJ; Laboratory Medical Immunology, Amsterdam UMC, Amsterdam, the Netherlands., Kootstra NA; Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Amsterdam, the Netherlands.; Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Zweegman S; Department of Hematology, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands.; Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands., Kater AP; Department of Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.; Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands., Heemskerk MHM; Department of Hematology, Leiden UMC, Leiden, the Netherlands., Groen K; Department of Hematology, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands., van Meerten T; Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Mutsaers PGNJ; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Beaumont T; Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., van Gils MJ; Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Goorhuis A; Department of Infectious Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Rutten CE; Department of Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Hazenberg MD; Department of Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.; Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Amsterdam, the Netherlands.; Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.; Department of Hematopoiesis, Sanquin Research, Amsterdam, the Netherlands., Nijhof IS; Department of Hematology, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands.; Department of Internal Medicine-Hematology, St Antonius Hospital, Nieuwegein, the Netherlands.
Jazyk:	angličtina
Zdroj:	JAMA oncology [JAMA Oncol] 2022 Oct 01; Vol. 8 (10), pp. 1477-1483.
DOI:	10.1001/jamaoncol.2022.3227
Abstrakt:	Importance: It has become common practice to offer immunocompromised patients with hematologic cancers a third COVID-19 vaccination dose, but data substantiating this are scarce. Objective: To assess whether a third mRNA-1273 vaccination is associated with increased neutralizing antibody concentrations in immunocompromised patients with hematologic cancers comparable to levels obtained in healthy individuals after the standard 2-dose mRNA-1273 vaccination schedule. Design, Setting, and Participants: This prospective observational cohort study was conducted at 4 university hospitals in the Netherlands and included 584 evaluable patients spanning the spectrum of hematologic cancers and 44 randomly selected age-matched adults without malignant or immunodeficient comorbidities. Exposures: One additional mRNA-1273 vaccination 5 months after completion of the standard 2-dose mRNA-1273 vaccination schedule. Main Outcomes and Measures: Serum immunoglobulin G (IgG) antibodies to spike subunit 1 (S1) antigens prior to and 4 weeks after a third mRNA-1273 vaccination, and antibody neutralization capacity of wild-type, Delta, and Omicron variants in a subgroup of patients. Results: In this cohort of 584 immunocompromised patients with hematologic cancers (mean [SD] age, 60 [11.2] years; 216 [37.0%] women), a third mRNA-1273 vaccination was associated with median S1-IgG concentrations comparable to concentrations obtained by healthy individuals after the 2-dose mRNA-1273 schedule. The rise in S1-IgG concentration after the third vaccination was most pronounced in patients with a recovering immune system, but potent responses were also observed in patients with persistent immunodeficiencies. Specifically, patients with myeloid cancers or multiple myeloma and recipients of autologous or allogeneic hematopoietic cell transplantation (HCT) reached median S1-IgG concentrations similar to those obtained by healthy individuals after a 2-dose schedule. Patients receiving or shortly after completing anti-CD20 therapy, CD19-directed chimeric antigen receptor T-cell therapy recipients, and patients with chronic lymphocytic leukemia receiving ibrutinib were less responsive or unresponsive to the third vaccination. In the 27 patients who received cell therapy between the second and third vaccination, S1 antibodies were preserved, but a third mRNA-1273 vaccination was not associated with significantly enhanced S1-IgG concentrations except for patients with multiple myeloma receiving autologous HCT. A third vaccination was associated with significantly improved neutralization capacity per antibody. Conclusions and Relevance: Results of this cohort study support that the primary schedule for immunocompromised patients with hematologic cancers should be supplemented with a delayed third vaccination. Patients with B-cell lymphoma and allogeneic HCT recipients need to be revaccinated after treatment or transplantation. Trial Registration: EudraCT Identifier: 2021-001072-41.
Databáze:	MEDLINE
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