Cardiotoxicity in cancer immunotherapy: a systematic review and global meta-analysis

OBJECTIVE: Cancer immunotherapy enhances the prognosis of cancer patients; however, it has been shown to be associated with potentially fatal cardiac risks, which requires further confirmation. This study aimed to explore the cardiotoxicity of immune checkpoint inhibitors (ICIs) in solid tumors. METHODS: A systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in the PROSPERO database, CRD42024614721. All randomized controlled trials (RCTs) comparing ICI with placebo and reporting complete adverse events in solid tumors were included. The primary outcome is the relative risk (RR) of cardiotoxicity for the purpose of discerning the disparities between the two groups. Data were pooled using random-effects model. RESULTS: A total of 101 RCTs involving 58,698 patients were included. The incidence of all-grade cardiotoxicity was 3.0% in the ICI group and 2.3% in the placebo group. The pooled relative risk for cardiotoxicity was higher with ICI compared with placebo (RR = 1.31, 95% CI = 1.17-1.48, P<0.001). Regarding individual cardiac adverse event, the pooled relative risks for myocarditis (RR = 1.79, 95%CI = 1.11-2.91, p = 0.018) and arrhythmia (RR = 1.22, 95%CI = 1.04-1.44, p = 0.016) were also higher with ICI compared with placebo. Sensitivity analysis demonstrated consistency in the overall estimate. CONCLUSIONS: Our study illustrated an increased cardiotoxicity of the use of ICI as single or combination regimens including myocarditis and arrhythmia based on a large number of the latest RCTs. More cautious attention should be paid on the ICIs-induced cardiotoxicities during cancer immunotherapy, especially for myocarditis and arrhythmia.