Fatal Myocarditis Induced by PD-1 Inhibitor as Second-line Therapy for Type B3 Thymoma：Case Report and Literature Review

Background: ： Thymoma and thymic carcinoma originate from thymic epithelial cells, with thymoma being the most prevalent thymic tumor [1]. Surgical intervention is the primary treatment for thymoma; however, many patients are diagnosed with advanced tumor stages, making complete resection challenging. Even after surgical removal, the recurrence rate remains high. Locally advanced or advanced thymoma patients require additional effective therapies, including radiotherapy and chemotherapy, to enhance prognosis. Immune checkpoint inhibitors have demonstrated promising anti-tumor effects in various cancer types and have shown efficacy in advanced or recurrent thymic tumors. Nevertheless, the incidence of adverse effects associated with immunotherapy is significantly higher in thymoma, particularly severe and fatal events. Therefore, the suitability of immune checkpoint inhibitors for thymoma treatment is still a subject of considerable controversy. Case Description: A 43-year-old male patient presented with a large tumor in the anterior mediastinum, as detected by enhanced chest CT. CT-guided percutaneous puncture biopsy confirmed the tumor as thymoma B3. Following evaluation by thoracic surgery, the tumor was deemed resectable, leading to a trans-thoracotomy procedure involving thymoma resection, superior vena cava plication, superior vena cava artificial vascular diversion, pericardiectomy, and right lower lung wedge resection. Intraoperatively, it was observed that the tumor had invaded the superior vena cava, resulting in an R1 resection status. Postoperatively, adjuvant chemotherapy combined with radiotherapy was recommended but declined by the patient. Instead, the patient received two cycles of intravenous chemotherapy with paclitaxel and cisplatin, which had to be discontinued due to intolerance. Immunohistochemical analysis revealed high PD-L1 expression in the tumor, indicating potential benefit from immunotherapy, particularly PD-1 inhibitors. After a detailed discussion regarding the PD-1 inhibitor regimen in combination with radiotherapy, the patient decided to proceed with PD-1 inhibitor therapy and provided informed consent for the treatment modification. Unfortunately, the patient experienced severe immune-related myocarditis 20 days after initiating PD-1 inhibitor immunotherapy, in addition to potential myasthenia gravis crisis and rapid onset of ventricular fibrillation. Despite extensive resuscitation efforts, including chest compressions, administration of medication to restore cardiac rhythm, and electrical defibrillation, the patient’s ventricular fibrillation persisted, ultimately leading to rapid demise. Conclusions: : Administration of PD-1 inhibitors in patients with thymoma has been observed to be associated with a heightened susceptibility to severe immune-related myocarditis, thus discouraging the use of PD-1 inhibitors as a customary therapeutic regimen for individuals with thymoma. In instances where their usage becomes imperative, rigorous monitoring of cardiac baseline levels, early identification, and timely intervention are imperative for the potential rescue of the patient’s life.