Myocarditis following the use of different immune checkpoint inhibitor regimens: A real-world analysis of post-marketing surveillance data

Abstract Backgrounds Although myocarditis has been reported in patients treated with immune checkpoint inhibitors (ICIs), there are few real-world studies to compare the occurrences and characteristics of myocarditis after different ICI regimens. Methods Disproportionality analysis and Bayesian analysis were utilized for data mining of the suspected adverse events of myocarditis after ICIs use based on the Food and Drug Administration's Adverse Event Reporting System (FAERS) from January 2004 to June 2018. The times to onset and fatality rates of myocarditis following different ICI regimens were also compared. Results A total of 315 reports of myocarditis adverse events were identified with ICIs. Among 6 ICI monotherapies, avelumab had the highest association with myocarditis based on the highest reporting odds ratio (ROR = 42.65, 95% two-sided CI = 15.86–114.72), proportional reporting ratio (PRR = 42.61, χ2 = 159.63) and empirical Bayes geometric mean (EBGM = 41.87, 95% one-sided CI = 15.57). The combination therapies of ipilimumab plus pembrolizumab or nivolumab had higher RORs, PRRs and EBGMs than did pembrolizumab or nivolumab monotherapy. Myocarditis associated with the ipilimumab plus nivolumab treatment appeared to have earlier onset (16.5 [IQR 14–29.75] days vs 32 [IQR 16–77] days, p Conclusions Analysis of FAERS data provides more precise profile on the occurrences and characteristics of myocarditis after different ICI regimens. The findings support continued surveillance, risk factor identification, and comparative studies.