Recommendations and exploration of diagnosis and treatment of critical and refractory immune checkpoint inhibitor‐associated adverse events

The application of immune checkpoint inhibitors (ICIs) has rewritten many malignant tumor treatment strategies and become another milestone in tumor treatment. This article summarizes the latest domestic and international guidelines and consensus regarding the diagnosis and treatment of grade 3–4 immune‐related adverse effects (irAEs). Included are the findings of annual meetings of the European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network/American Society for Clinical Oncology (NCCN/ASCO), the Society for Immunotherapy of Cancer (SITC), and the Chinese Society of Clinical Oncology (CSCO) with review of case reports and related reviews of irAEs that were published before 20 May 2019. The recommendations for the diagnosis and treatment of irAEs are supplemented, highlighting the successful application of specific immunosuppressive drugs in different irAEs, including IL‐6 blockade, anti‐CD20 monoclonal antibody, antitumor necrosis factor alpha and anti‐integrin 4 monoclonal antibodies, thrombopoietin receptor agonist, and antithymocyte globulin. This article questions the use of steroid hormones for irAEs in ultra‐large doses, upgrades, and repeated use, and emphasizes that it is important to note secondary infections, tumor progression, and the inability to meet the challenges of ICIs. Herein, we propose the principle of “stepping down treatment” for critical and refractory irAEs, and suggest that the use of specific immunosuppressive drugs such as cytokine‐targeted drugs should be initiated as soon as possible. Many irAEs in the era of immunotherapy are unprecedented in the era of traditional chemotherapy and small molecule targeted therapy, and this constantly challenges the knowledge reserve and clinical skills of oncologists. Therefore, the establishment of a multidisciplinary discussion system for cancer is extremely important.