Cardiotoxicity associated with immune checkpoint inhibitors: Systematic review and meta-analysis

Background and aims: The aim of this systematic review was to assess the risk of cardiac toxicity in patients undergoing approved PD-1 (nivolumab, pembrolizumab, cemiplimab, dostarlimab), PD-L1 (atezolizumab, avelumab, durvalumab), and CTLA-4 (ipilimumab) inhibitors. Results: Among a total of 2272 articles, 11 phase II and III clinical trials included: 5463 patients and 175 cardiac adverse events. The most common cardiac disorder was atrial fibrillation (12 %), while cardiac arrest and cardiac failure (6%) led to death in three cases. Overall, ICI treatment increased the risk of cardiotoxicity compared with control groups (RR=1.62, 95 %-CI= 1.18-2.24, p-value=0.0033; OR=1.71, 95 %-CI= 1.20-2.42, pvalue=0.0027). Conclusions: This study proved that the recognition of frequency and severity of all grade cardiotoxicity associated with ICIs is still underestimated. Thus, a systematic cardiological screening becomes necessary, in order to intercept the potential cardiological complications beforehand and optimize the outcomes of the respective treatment with PD-1, PD-L1 and CTLA-4 inhibitors.