Co-occurring infections in cancer patients treated with checkpoint inhibitors significantly increase the risk of immune related adverse events.

Autor:	Makunts T; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, United States., Grabska S; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, United States.; Institute of Biomedicine and Pharmacy, RAU, Yerevan, 0051, Armenia.; L.A. Orbeli Institute of Physiology, National Academy of Sciences, Yerevan, 0028, Armenia., Grabski H; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, United States.; Institute of Biomedicine and Pharmacy, RAU, Yerevan, 0051, Armenia.; L.A. Orbeli Institute of Physiology, National Academy of Sciences, Yerevan, 0028, Armenia., Abagyan R; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, United States.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2024 Feb 15. Date of Electronic Publication: 2024 Feb 15.
DOI:	10.1101/2024.02.14.24302840
Abstrakt:	Therapeutic antibodies designed to target immune checkpoint proteins such as PD-1, PD-L1, and CTLA-4 have been applied in the treatment of various tumor types, including small and non-small cell lung cancers, melanoma, renal cell carcinoma, and others. These treatments combat cancers by reactivating CD8 cytotoxic T-cells. Nevertheless, this unique targeted mode of action was found to be associated with a broader range of immune-related adverse events, irAEs, affecting multiple physiological systems. Depending on their severity, these irAEs often necessitate the suspension or discontinuation of treatment and, in rare instances, may lead to fatal consequences. In this study we investigated over eighty thousand adverse event reports of irAEs in patients treated with PD-1, PD-L1, and CTLA-4 inhibitors. FDA Adverse Event Reporting System MedWatch submissions were used as the data source. These therapeutics included pembrolizumab, nivolumab, cemiplimab, avelumab, durvalumab, atezolizumab, and ipilimumab. The data analysis of these reports revealed a statistically significant association of immune related adverse events, including serious and life-threatening events in patients who experienced infectious disease during treatment. Additionally, the association trend was preserved across all the three classes of checkpoint inhibitors and each of the seven individual therapeutic agent cohorts. Competing Interests: Conflicts of interest The authors declare that they have no conflicts of financial or non-financial interest.
Databáze:	MEDLINE
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