[Treatment with PD-1/PD-L1 and CTLA-4 immune checkpoint inhibitors : Immune-mediated side effects]

Immune checkpoint inhibitors are a new standard therapy for advanced or metastatic urothelial as well as renal cell carcinoma. Atezolizumab and Pembrolizumab have been approved for the treatment of cisplatin-ineligible patients with transitional call cancer in the 1st line setting; both antibodies and Nivolumab may also be used after platinum based prior therapy. Regarding renal cell carcinoma approval for 1st line treatment with the combination of Nivolumab and Ipilimumab for patients at intermediate or high risk (IMDC) is currently expected. Furthermore, Nivolumab is approved for renal cell carcinoma after prior therapy. With the widespread use of immune checkpoint inhibitors understanding immune related adverse events gets paramount importance. In particular, combination therapy of Nivolumab and Ipilimumab is not only characterized by improving efficacy but also by a higher rate of adverse events. Most frequently rash and pruitus, endocrine events, colitis/diarrhea, hepatitis and pneumonia are observed. However, any organ system may be affected by immune related adverse events. Differential diagnosis between immune related or other (e. g. infectious) causes of organ dysfunction may be difficult. Early diagnosis and initiation of therapy is important to avoid deleterious outcomes. The use of corticosteroids generally leads to rapid resolution of symptoms; further immunosuppressive agents (MMF, infliximab) are rarely needed. Regarding endocrine adverse events permanent hormonal replacement of hormones is frequently needed. In particular in consequence of pneumonitis fatal outcomes have been observed.