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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-96467-5 |
| _version_ | 1818422578317885440 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T13:28:29Z |
| format | Article |
| id | doaj.art-f9e5c40ece6d4172afc9cd95cfa7fd22 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T13:28:29Z |
| publishDate | 2021-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f9e5c40ece6d4172afc9cd95cfa7fd222022-12-21T22:59:47ZengNature PortfolioScientific Reports2045-23222021-08-0111111510.1038/s41598-021-96467-5Myocarditis occurrence with cancer immunotherapy across indications in clinical trial and post-marketing dataTigran Makunts0Ila M. Saunders1Isaac V. Cohen2Mengxing Li3Talar Moumedjian4Masara A. Issa5Keith Burkhart6Peter Lee7Sandip Pravin Patel8Ruben Abagyan9Oak Ridge Institute of Science and Education Fellowship at Office of Clinical Pharmacology, United States Food and Drug AdministrationSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San DiegoClinical Pharmacology and Therapeutics (CPT) Postdoctoral Training Program, University of California San FranciscoOak Ridge Institute of Science and Education Fellowship at Office of Clinical Pharmacology, United States Food and Drug AdministrationSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San DiegoSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San DiegoCenter for Drug Evaluation and Research, US Food and Drug AdministrationCenter for Drug Evaluation and Research, US Food and Drug AdministrationCenter for Personalized Cancer Therapy, Division of Hematology and Medical Oncology, UCSD Moores Cancer CenterSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San DiegoAbstract 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.https://doi.org/10.1038/s41598-021-96467-5 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-96467-5 |
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