Fatal adverse events in two thymoma patients treated with anti-PD-1 immune check point inhibitor and literature review

Objectives: Thymomas, as well as thymic carcinomas, are extremely rare tumors that arise from the thymus. The management of these tumors is primarily the complete surgical resection, however when there is tumor progression or metastatic unresectable disease, palliative platinum-based chemotherapy is the standard of care. On this setting, alternative options are emerging including immune checkpoints inhibitors. Based on that, PDL-1 expression was measured in thymic tumors as a potential predictive biomarker of response to anti-PD1 and anti-PDL1 immune inhibitors. Our objective is to report the first two cases of fatal toxicity due to anti-PD1 therapy in thymoma patients. Materials and Methods: Here, we report two cases of metastatic B2/B3 thymomas refractory to initial standard chemotherapy treatment, with high PDL1 expression (> 50%), that were treated with the anti-PD1 agent, pembrolizumab. Results: The administration of anti-PD1 immune check point inhibitor resulted in a storm of immune related adverse events including myositis, myocarditis and myasthenia gravis and death after administration of the first treatment cycle. Conclusion: In thymomas, the administration of PD1 inhibitors seems to be associated with a high percentage of severe immune related adverse events, thus requiring special caution on the usage of these agents in thymomas.