Fatal toxicity induced by anti-PD-1 immune checkpoint inhibitor in thymic epithelial tumor

A standard treatment for advanced thymic epithelial tumors (TETs) after initial treatment remains unavailable to date. Targeted immune checkpoint inhibitors (ICIs) of the programmed cell death-1 (PD-1) pathway may produce objective responses in TETs, notably thymic carcinoma. Findings of clinical trials suggested ICIs are a practical choice. However, the risk of severe immuno-related adverse events is higher in TETs. Concerning histologic subtypes, thymomas are more frequently associated with autoimmune disorders than carcinomas, so close monitoring is needed for thymomas. In this article, we describe four cases of fatal toxicity caused by anti-PD-1 therapy in TETs. Four patients with metastatic thymomas or carcinoma difficult to treat with first-line standard chemotherapy were treated with the anti-PD-1 drug pembrolizumab or sintilimab. The association of PD-1 inhibitors with a high proportion of severe immuno-related adverse events in TETs necessitates attentive monitoring during treatment. Thymic epithelial tumors are the most common malignancy of the anterior mediastinum in adults, with the occurrence of approximately 1.5 cases/million. Surgery is usually the treatment of choice. However, treatment options for advanced disease are poorly understood, and data are limited. Several studies have assessed the objective responses of immune checkpoint inhibitors in patients with advanced thymic epithelial tumors. Anti-cancer immunity also increases the risk of developing adverse events related to immunotherapy. Some patients can experience lethal toxicity. This article presents four cases of developing severe adverse events to exercise caution in prescribing these agents for thymic epithelial tumor, in particular thymoma.