Cardiotoxicity of immune checkpoint inhibitors: A retrospective cohort study of 93,362 patients.

e14529 Background: The advent of immune checkpoint inhibitors (ICI) as therapy for a wide array of cancer types has extended patient survival and propelled the field of oncology into a new era. However, notable immune-related adverse events have been observed that transgress self-tolerance. Among these adverse events, myocarditis is emerging as a serious and often lethal toxicity. This study aims to assess whether a significant association exists between immune checkpoint inhibitors and myocarditis and/or pericarditis. Methods: The TriNetX research network was used for this study. Two patient cohorts were created by using International Classification of Disease 10 (ICD-10) codes and HCPCS codes. Both patient cohorts consisted of patients with malignancy (C00-D49) and no history of myocarditis. One cohort was treated with immunotherapy while the other was excluded from such exposure (HCPCS codes were used for ipilimumab, nivolumab, pembrolizumab, and durvalumab). The cohorts were balanced for age, race, gender, and ethnicity by propensity score matching and the greedy nearest neighbor algorithm, resulting in 46,681 patients in each arm. They were then evaluated for the development of myocarditis or pericarditis (I51.4, I31, I30) over the subsequent 5 years. Results: Cancer patients treated with immunotherapy were significantly more likely to experience myocarditis or pericarditis than those who did not receive those agents (7% vs 1.2%, RR 5.8, 95% CI (5.33,6.36), P value <0.0001). Conclusions: This study suggests a significant association between the use of immunotherapy agents and the development of myocarditis and pericarditis. Further studies are necessary to better delineate the mechanism by which these cardiac toxicities occur, establish guidelines for surveillance of its onset, and discover how to suppress the immune-toxicities while retaining anti-tumor effect.