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

• Published in: Scientific reports Vol. 11; no. 1; p. 17324
• Main Authors: Makunts, Tigran, Saunders, Ila M., Cohen, Isaac V., Li, Mengxing, Moumedjian, Talar, Issa, Masara A., Burkhart, Keith, Lee, Peter, Patel, Sandip Pravin, Abagyan, Ruben
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.08.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67; 631/67/1059; 631/67/1059/2325; 692/4019/592/75/74; 692/4028; 692/4028/67; 692/4028/67/1059; 692/4028/67/1059/2325; 692/700/565/2194; 692/700/565/251; Adverse Drug Reaction Reporting Systems; Adverse events; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; Antitumor agents; Cancer; Cancer immunotherapy; Chemotherapy; Clinical trials; CTLA-4 protein; Data Collection; Enzyme inhibitors; Heart diseases; Humanities and Social Sciences; Humans; Immune Checkpoint Inhibitors; Immune response; Immune system; Immunotherapy; Immunotherapy - adverse effects; multidisciplinary; Myocarditis; Myocarditis - complications; Myocarditis - etiology; Neoplasms - complications; Neoplasms - therapy; Odds Ratio; Patients; PD-1 protein; PD-L1 protein; Retrospective Studies; Science; Science (multidisciplinary); Statistical analysis; United States; United States Food and Drug Administration; United States
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-96467-5

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.