== Characteristics of the patients. == 3.2. at a tertiary care center were analyzed retrospectively. Adverse events were coded by CTCAE version 5.0. The Croverin course and frequency of irAEs were summarized using descriptive statistics. A total of 406 patients were included in the study. In 44.6% (n = 181) of patients, 229 irAEs were documented. Out of those, 146 irAEs (63.8%) were treated with systemic steroids. Sr-irAEs and sd-irAEs (n = 25) were detected in 10.9% of all irAEs, and in 6.2% of ICI-treated patients. In this cohort, infliximab (48%) and mycophenolate mofetil (28%) were most often administered as second-line immunosuppressants. The type of irAE was the most important factor associated with the choice of second-line immunosuppression. The Sd/sr-irAEs resolved in 60% of cases, had permanent sequelae in 28% of cases, and required third-line therapy in 12%. None of the irAEs were fatal. Croverin Although these side effects manifest in only 6.2% of patients under ICI therapy, they impose difficult therapy decisions, especially since you will find few data to determine the optimal second-line immunosuppression. Keywords:steroid-refractory immune-related adverse events, steroid-dependent immune-related adverse events, skin malignancy, second-line immunosuppression == 1. Introduction == Immune checkpoint inhibitors (ICIs) have become standard therapy for many tumor entities. They target the PD1-/PD-L1 pathway, the CTLA-4 pathway, or the LAG-3 pathway and are either used as monotherapy or in combination, e.g., Croverin with different ICI or chemotherapy [1]. Along with the improved clinical outcome, severe toxicities or so-called immune-related adverse events (irAEs) are induced. Grade 3 and 4 side effects were observed in 642% of patients treated with anti-PD1 or anti-PDL1-antibodies [2,3,4,5], in 28% of patients treated with Croverin ipilimumab [6], in 59% of patient treated with combined ipilimumab and nivolumab [6], and in 19% of patients with combined relatlimab and nivolumab according to CTCAE version 5.0 [7]. Systemic corticosteroids are considered the first-line therapy for the management of irAEs in most organ systems [8,9,10]. However, a subgroup of patients with irAEs does not adequately respond to steroids and have so-called steroid-refractory side effects (sr-irAEs), or cannot be tapered off steroids without the recurrence of side effects, called steroid-dependent side effects (sd-irAEs). In sr-irAEs and sd-irAEs, numerous second-line immunosuppressants have been suggested and used. Depending on the affected organ, recommendations range from classical systemic immunosuppressants such as mycophenolate mofetil, cyclosporine A, methotrexate or azathioprine, monoclonal antibodies targeting tumor necrosis factor alpha (TNF-, infliximab), 47-integrin (vedolizumab), or CD20 (rituximab), and intravenous immunoglobulins, antithymocyte globulin or plasmapheresis. There are little data available on the immunologic mechanisms of irAEs to date, however, CRP and interleukin 6 (IL-6) are clearly upregulated [11], and the anti-IL6 receptor antibody tocilizumab was also shown to be effective [12]. Alemtuzumab, an anti-CD52 monoclonal antibody, was recently shown to be effective in a single case of immune-related myocarditis [13], and abatacept, a CTLA-4 agonist which leads to an inhibition of CD28-B7-mediated T-cell costimulation, has also shown potential [14]. In a patient with immune-related colitis refractory to corticosteroids, infliximab and cyclosporine in combination with extracorporeal photopheresis led to the resolution of symptoms and the growth of natural killer cells with an immunoregulatory phenotype [15]. Two patients with irColitis, who failed to respond to both systemic steroids and vedolizumab, were effectively treated with the anti-IL12/IL23 antibody ustekinumab [16]. The blockade of IL17A with secukinumab successfully PIK3C1 led to the improvement in pain and swelling in two patients with immune-related inflammatory arthropathy and to resolution in one patient with a psoriasiform exanthema which worsened after tapering systemic steroids [17,18]. However, to date, management decisions.