Myocarditis occurrence with cancer immunotherapy across indications in clinical trial and post-marketing data

Abstract Antibodies targeting the PD-1, PD-L1, and CTLA-4 immune checkpoint axis have been used in a variety of tumor types. They achieve anti-tumor activity through activating the patient’s own immune system to target immune response evading cancer cells. However, this unique mechanism of action ma...

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Autores principales:	Tigran Makunts, Ila M. Saunders, Isaac V. Cohen, Mengxing Li, Talar Moumedjian, Masara A. Issa, Keith Burkhart, Peter Lee, Sandip Pravin Patel, Ruben Abagyan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f9e5c40ece6d4172afc9cd95cfa7fd22
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spelling	oai:doaj.org-article:f9e5c40ece6d4172afc9cd95cfa7fd222021-12-02T16:37:37ZMyocarditis occurrence with cancer immunotherapy across indications in clinical trial and post-marketing data10.1038/s41598-021-96467-52045-2322https://doaj.org/article/f9e5c40ece6d4172afc9cd95cfa7fd222021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96467-5https://doaj.org/toc/2045-2322Abstract Antibodies targeting the PD-1, PD-L1, and CTLA-4 immune checkpoint axis have been used in a variety of tumor types. They achieve anti-tumor activity through activating the patient’s own immune system to target immune response evading cancer cells. However, this unique mechanism of action may cause immune-related adverse events, irAEs. One of these irAEs is myocarditis which is associated with an alarming mortality rate. In this study we presented clinical cases of myocarditis from safety trial datasets submitted to the U.S. Food and Drug Administration, FDA. Additionally, we analyzed over fourteen million FDA Adverse Event Reporting System, FAERS, submissions. The statistical analysis of the FAERS data provided evidence of significantly increased reporting of myocarditis in patients administered immune checkpoint inhibitors alone, in combination with another immune checkpoint inhibitor, the kinase inhibitor axitinib, or chemotherapy, for all cancer types, when compared to patients administered chemotherapy. All combination therapies led to further increased reporting odds ratios of myocarditis. We further analyzed the occurrence of myocarditis by stratifying the reports into sub-cohorts based on specific cancer types and treatment/control groups in major cancer immunotherapy efficacy trials and confirmed the observed trend for each cohort.Tigran MakuntsIla M. SaundersIsaac V. CohenMengxing LiTalar MoumedjianMasara A. IssaKeith BurkhartPeter LeeSandip Pravin PatelRuben AbagyanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tigran Makunts Ila M. Saunders Isaac V. Cohen Mengxing Li Talar Moumedjian Masara A. Issa Keith Burkhart Peter Lee Sandip Pravin Patel Ruben Abagyan Myocarditis occurrence with cancer immunotherapy across indications in clinical trial and post-marketing data
description	Abstract Antibodies targeting the PD-1, PD-L1, and CTLA-4 immune checkpoint axis have been used in a variety of tumor types. They achieve anti-tumor activity through activating the patient’s own immune system to target immune response evading cancer cells. However, this unique mechanism of action may cause immune-related adverse events, irAEs. One of these irAEs is myocarditis which is associated with an alarming mortality rate. In this study we presented clinical cases of myocarditis from safety trial datasets submitted to the U.S. Food and Drug Administration, FDA. Additionally, we analyzed over fourteen million FDA Adverse Event Reporting System, FAERS, submissions. The statistical analysis of the FAERS data provided evidence of significantly increased reporting of myocarditis in patients administered immune checkpoint inhibitors alone, in combination with another immune checkpoint inhibitor, the kinase inhibitor axitinib, or chemotherapy, for all cancer types, when compared to patients administered chemotherapy. All combination therapies led to further increased reporting odds ratios of myocarditis. We further analyzed the occurrence of myocarditis by stratifying the reports into sub-cohorts based on specific cancer types and treatment/control groups in major cancer immunotherapy efficacy trials and confirmed the observed trend for each cohort.
format	article
author	Tigran Makunts Ila M. Saunders Isaac V. Cohen Mengxing Li Talar Moumedjian Masara A. Issa Keith Burkhart Peter Lee Sandip Pravin Patel Ruben Abagyan
author_facet	Tigran Makunts Ila M. Saunders Isaac V. Cohen Mengxing Li Talar Moumedjian Masara A. Issa Keith Burkhart Peter Lee Sandip Pravin Patel Ruben Abagyan
author_sort	Tigran Makunts
title	Myocarditis occurrence with cancer immunotherapy across indications in clinical trial and post-marketing data
title_short	Myocarditis occurrence with cancer immunotherapy across indications in clinical trial and post-marketing data
title_full	Myocarditis occurrence with cancer immunotherapy across indications in clinical trial and post-marketing data
title_fullStr	Myocarditis occurrence with cancer immunotherapy across indications in clinical trial and post-marketing data
title_full_unstemmed	Myocarditis occurrence with cancer immunotherapy across indications in clinical trial and post-marketing data
title_sort	myocarditis occurrence with cancer immunotherapy across indications in clinical trial and post-marketing data
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f9e5c40ece6d4172afc9cd95cfa7fd22
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Myocarditis occurrence with cancer immunotherapy across indications in clinical trial and post-marketing data

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