Pembrolizumab-induced myocarditis: A systematic review of case reports.

Abstract

e14605 Background: Immune checkpoint inhibitors, such as pembrolizumab, have revolutionized cancer therapy but are associated with immune-related adverse events (irAEs), including myocarditis, which can have serious clinical consequences. This systematic review aims to comprehensively analyze case reports to better understand pembrolizumab-induced myocarditis. Methods: Using keywords of "pembrolizumab" or "Keytruda" and "myocarditis" in the PubMed/Medline, ScienceDirect and clinicaltrials.gov databases and manual searches on Google Scholar, we reviewed all cases reported up to the year 2023. In total, 296 studies received primary screening. Duplicated articles and those meeting the exclusion criteria (not myocarditis, not human, not English, trials done in vitro, combination immunotherapies) were excluded. Review articles, retrospective studies, systematic reviews, and meta-analyses were also excluded. Finally, 45 studies matching the inclusion criteria were included (total of 46 patients). Data on patient demographics, clinical presentation, diagnostic criteria, management strategies, and outcomes were extracted and analyzed. Results: In the included 46 patients, the mean age was 65.5 years, with a slight male predominance (56.5%). Predominant cancer types included lung cancer (30.4%), thymoma (15.2%), melanoma (13.0%), and genitourinary cancers (13.0%). 45.7% of patients developed myocarditis after their first cycle of Pembrolizumab while 41.3% developed myocarditis after two cycles. 47.8% of patients presented with dyspnea, 23.9% with fatigue, 10.9% with chest pain, while 13% of the patients were asymptomatic and were subsequently diagnosed with myocarditis while presenting with other immune-related adverse events. Troponin levels were assessed in 45 individuals, with only 2.2% (one patient) having normal levels. ECG changes included ST segment elevation in 21.7%, conduction abnormalities (RBBB 15.2%, LBBB 6.5%, AV block 26.1%, and one unspecified conduction abnormality) in 50%, and arrhythmias in 37% of cases. Treatment included steroids for all, with varying outcomes. Four patients each received one of the following treatments: batacept, ruxolitinib, alemtuzumab, and methotrexate. All four of these patients showed improvement. Two patients received infliximab (4.3%) and both of them died. Outcomes revealed 34.8% mortality, 63.0% improvement, and 2.2% deterioration, including one sudden cardiac death 35 days post-discharge. Conclusions: Pembrolizumab-induced myocarditis is a rare but potentially life-threatening irAE. This systematic review provides a comprehensive overview of the clinical characteristics, diagnostic challenges, treatment approaches, and outcomes of this condition. Further research is needed to elucidate the underlying mechanisms and identify risk factors for pembrolizumab-induced myocarditis, enabling early detection and prevention strategies.