Cardiotoxicity of pembrolizumab therapy: narrative review

Pembrolizumab, a programmed cell death protein 1 inhibitor, has had a substantial impact on cancer treatment across multiple malignancies, but is associated with immune-related cardiovascular toxicities that pose significant clinical challenges. Complications such as myocarditis, arrhythmias, and cardiomyopathy are emerging as significant entities with high morbidity and mortality. This article is a narrative review and was not designed or conducted as a systematic review. No formal systematic review protocol was followed and attempts to identify or include all published studies on this topic were not undertaken. The goal is to provide a clinically oriented synthesis of the current literature on pembrolizumab-associated cardiotoxicity. A literature search was conducted using PubMed, Medline, and Google Scholar databases for articles published between January 2014 and March 2025. Search terms included ‘pembrolizumab,’ ‘PD-1 inhibitor,’ ‘immune checkpoint inhibitor,’ ‘cardiotoxicity,’ ‘myocarditis,’ ‘pericarditis,’ ‘arrhythmia,’ and ‘cardiac adverse events,’ used individually and in combination. Inclusion criteria encompassed English-language clinical trials, observational studies, systematic reviews, meta-analyses, pharmacovigilance analyses, clinical practice guidelines, and case reports involving human subjects. Non-English publications, preclinical studies without clinical correlates, and editorials without original data were excluded. Reference lists of identified articles were manually reviewed to identify additional relevant publications. Study selection was performed by a single author. Pembrolizumab-induced myocarditis, although rare, carries a high mortality rate and typically presents within the first few weeks of treatment, including a relative risk of myocarditis ~4.5 with combination immune checkpoint inhibitor therapy. Proposed mechanisms of this cardiotoxicity, though not settled, include shared antigenic targets between tumor and cardiac tissue and impaired immune tolerance. Current management relies on prompt recognition, immunosuppression with high-dose IV methylprednisolone as first-line therapy, and additional immunomodulatory agents for refractory cases. Emerging evidence from case reports and small cohort studies suggests potential benefit from abatacept with ruxolitinib in steroid-refractory cases; however, prospective validation is needed. Baseline cardiac screening and serial monitoring of cardiac biomarkers including high-sensitivity troponin and NT-proBNP, and a multidisciplinary cardio-oncology approach are essential for early detection and optimal outcomes.