Results:

The study authors reported that the prevalence of myocarditis was 1.14% with a median time of onset of 34 days after starting ICI (interquartile range, 21-75). The mean age of the study cohort was 65 ± 13 years of age, 29% were female, and 54% had no other immune-related side effects. The most common indications for ICI were melanoma and non-small cell lung cancer. All cases with ICI-associated myocarditis had ICIs permanently discontinued. Compared with controls, myocarditis cases were more likely to have received combination ICI at any stage in treatment and were more likely to be treated with combination ICI therapy at the time of statistical analysis, that is, a median of 281 days of follow-up for controls, and 209 days for myocarditis cases.

Of the combination therapies at the time of presentation, anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) with anti-programmed cell death protein 1 (anti-PD1) was the most frequent in cases. However, overall, myocarditis was more commonly seen with concurrent single ICI therapy (66%). Relative to controls, combination ICI (34% vs. 2%; p < 0.001) and diabetes (34% vs. 13%; p = 0.01) were more common in cases. Before myocarditis, the pre-ICI left ventricular ejection fraction was ≥50% in all those with a baseline measurement. In comparison with controls, myocarditis cases had a higher prevalence of diabetes mellitus and sleep apnea, and a higher body mass index. Over 102 days (interquartile range, 62-214) of median follow-up, 16 (46%) developed MACE; 38% of MACE occurred with normal ejection fraction. There was a four-fold increased risk of MACE with troponin T of ≥1.5 ng/ml (hazard ratio, 4.0; 95% confidence interval, 1.5-10.9; p = 0.003). Steroids were administered in 89%, and lower steroid doses were associated with higher residual troponin and higher MACE rates.