Effects of antineoplastic and immunomodulating agents on postvaccination SARS-CoV-2 breakthrough infections, antibody response, and serological cytokine profile.

Autor:	New J; Medicine, Scripps Health, La Jolla, California, USA.; Scripps Research Translational Institute, La Jolla, California, USA., Cham J; Scripps Research Translational Institute, La Jolla, California, USA., Smith L; Scripps Research Translational Institute, La Jolla, California, USA., Puglisi L; Medicine, Scripps Health, La Jolla, California, USA., Huynh T; Scripps Research Translational Institute, La Jolla, California, USA.; Division of Hematology/Oncology, University of California, La Jolla, California, USA., Kurian S; Scripps Organ Transplantation Research & Biorepository, Scripps Health, La Jolla, California, USA., Bagsic S; Medicine, Scripps Health, La Jolla, California, USA., Fielding R; Strategy & Planning, Scripps Health, La Jolla, California, USA., Hong L; Medicine, Scripps Health, La Jolla, California, USA.; Scripps Research Translational Institute, La Jolla, California, USA., Reddy P; Medicine, Scripps Health, La Jolla, California, USA., Eum KS; Medicine, Scripps Health, La Jolla, California, USA.; Rheumatology, Veterans Administration Pacific Islands Healthcare System, Honolulu, Hawaii, USA., Martin A; Scripps Organ Transplantation Research & Biorepository, Scripps Health, La Jolla, California, USA., Barrick B; Scripps Organ Transplantation Research & Biorepository, Scripps Health, La Jolla, California, USA., Marsh C; Scripps Organ Transplantation Research & Biorepository, Scripps Health, La Jolla, California, USA., Quigley M; Pathology, Scripps Health, La Jolla, California, USA., Nicholson LJ; Medicine, Scripps Health, La Jolla, California, USA apandey@tulane.edu nicholson.laura@scrippshealth.org.; Scripps Research Translational Institute, La Jolla, California, USA., Pandey AC; Scripps Research Translational Institute, La Jolla, California, USA apandey@tulane.edu nicholson.laura@scrippshealth.org.; Medicine, Section of Cardiology, Tulane University, New Orleans, Louisiana, USA.; Medicine, Southeast Veterans Health Care System, New Orleans, Louisiana, USA.
Jazyk:	angličtina
Zdroj:	Journal for immunotherapy of cancer [J Immunother Cancer] 2024 Jan 31; Vol. 12 (1). Date of Electronic Publication: 2024 Jan 31.
DOI:	10.1136/jitc-2023-008233
Abstrakt:	Background: Despite immunization, patients on antineoplastic and immunomodulating agents have a heightened risk of COVID-19 infection. However, accurately attributing this risk to specific medications remains challenging. Methods: An observational cohort study from December 11, 2020 to September 22, 2022, within a large healthcare system in San Diego, California, USA was designed to identify medications associated with greatest risk of postimmunization SARS-CoV-2 infection. Adults prescribed WHO Anatomical Therapeutic Chemical (ATC) classified antineoplastic and immunomodulating medications were matched (by age, sex, race, and number of immunizations) with control patients not prescribed these medications yielding a population of 26 724 patients for analysis. From this population, 218 blood samples were collected from an enrolled subset to assess serological response and cytokine profile in relation to immunization. Results: Prescription of WHO ATC classified antineoplastic and immunomodulatory agents was associated with elevated postimmunization SARS-CoV-2 infection risk (HR 1.50, 95% CI 1.38 to 1.63). While multiple immunization doses demonstrated a decreased association with postimmunization SARS-CoV-2 infection risk, antineoplastic and immunomodulatory treated patients with four doses remained at heightened risk (HR 1.23, 95% CI 1.06 to 1.43). Risk variation was identified among medication subclasses, with PD-1/PD-L1 inhibiting monoclonal antibodies, calcineurin inhibitors, and CD20 monoclonal antibody inhibitors identified to associate with increased risk of postimmunization SARS-CoV-2 infection. Antineoplastic and immunomodulatory treated patients also displayed a reduced IgG antibody response to SARS-CoV-2 epitopes alongside a unique serum cytokine profile. Conclusions: Antineoplastic and immunomodulating medications associate with an elevated risk of postimmunization SARS-CoV-2 infection in a drug-specific manner. This comprehensive, unbiased analysis of all WHO ATC classified antineoplastic and immunomodulating medications identifies medications associated with greatest risk. These findings are crucial in guiding and refining vaccination strategies for patients prescribed these treatments, ensuring optimized protection for this susceptible population in future COVID-19 variant surges and potentially for other RNA immunization targets. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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