Fatal Fulminant Myocarditis Following a Single Dose of Pembrolizumab in a Patient with Recurrent Thymoma: A Case Report

Background and Objectives Thymic epithelial tumors often present with autoimmune disorders. While PD-L1–targeting immune checkpoint inhibitors (ICIs) like pembrolizumab offer therapeutic potential, they risk severe myocarditis. We report fatal ICI-induced myocarditis after a single dose, underscoring the need for close monitoring in thymoma patients. Case Presentation A 31-year-old male with type B1/B2 thymoma (pT3, Masaoka stage 3) underwent surgical resection and received adjuvant radiotherapy. After disease relapse, he received six cycles of CAP chemotherapy (cyclophosphamide 500 mg/m 2 , Adriamycin 50 mg/m 2 , cisplatin 50 mg/m 2 ) and showed stable disease. Due to 60% PD-L1 expression, pembrolizumab was initiated. One week post-first dose, he presented with chest pain and dyspnea. Workup revealed elevated troponin, ST-segment elevations, and normal echocardiography, consistent with myocarditis. Despite high-dose steroids and intensive care, he rapidly deteriorated, developing ventricular fibrillation and passed away within 24 h. Conclusion This case underscores the lethal synergy between thymoma’s immunogenic milieu and ICI toxicity, particularly myocarditis. The rapid progression to fatal arrhythmia after a single pembrolizumab dose suggests that thymoma patients may require enhanced cardiac monitoring protocols pre- and post-ICI initiation. Further research is needed to identify risk stratification biomarkers and optimize immunosuppression strategies for this high-risk population.