Immune-checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte antigen 4 (CTL A-4), anti-programmed cell death 1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are arguably the most important development in cancer therapy over the past decade. The indications for these agents continue to expand across malignancies and disease settings, thus reshaping many of the previous standard-of-care approaches and bringing new hope to patients. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), which are often distinctly different from the classical chemotherapy-related toxicities. Owing to the growing use of ICIs in oncology, clinicians will increasingly be confronted with common but also rare irAEs; hence, awareness needs to be raised regarding the clinical presentation, diagnosis and management of these toxicities. In this Review, we provide an overview of the various types of irAEs that have emerged to date. We discuss the epidemiology of these events and their kinetics, risk factors, subtypes and pathophysiology, as well as new insights regarding screening and surveillance strategies. We also highlight the most important aspects of the management of irAEs.

Results. The mean ؎ SD followup was 56.2 ؎ 31.7 months. Among the 72 patients studied, 93% achieved remission with CS therapy alone, and 35% relapsed, mainly during the first year of treatment. Among the 19 patients randomized to additional immunosuppression because of treatment failure or relapse, 5 of 10 receiving AZA and 7 of 9 receiving pulse CYC achieved remission, but the difference was not statistically significant. Survival rates in all patients at 1 and 5 years were 100% and 97%, respectively. At the end of followup, 79% of the patients whose disease was in remission required lowdose CS therapy, mainly to control respiratory disease. CS-related adverse events were observed in 31% of the 72 patients.Conclusion. In CSS patients with an FFS of 0, survival was excellent, confirming the predictive value of the FFS in this disease. First-line therapy with CS achieved remission in most patients, but relapses were common, and one-third of them required additional immunosuppressive therapy. AZA or pulse CYC was fairly effective in treating CS-resistant disease or major relapses. Over the long term, most patients continued to take oral CS, which might explain the high rate of CS-related adverse events.Churg-Strauss syndrome (CSS), which is also called allergic granulomatosis and angiitis, is characterized by necrotizing eosinophilic vasculitis affecting the small vessels and extravascular granulomas. The major clinical manifestations are asthma, hypereosinophilia, and extrapulmonary manifestations of systemic vasculitis. Antineutrophil cytoplasmic antibodies (ANCAs), ClinicalTrials.gov identifier: NCT00399399.

Immune-checkpoint inhibitors (ICIs) are reshaping the prognosis of many cancer types and are progressively becoming a standard of care for many of them. Cancer immunotherapy has started a revolution in the oncology therapeutic landscape, bringing new hope to patients but also a whole new spectrum of toxicities for practitioners to manage. Oncologists and specialists involved in the pluridisciplinary management of immune-related adverse events (irAEs) are increasingly confronted with the therapeutic challenge of severe and/or refractory cases. In this personal view, we summarize the therapeutic strategies reported to manage them. Based on current knowledge of irAE pathogenesis and our immunological expertise, we also transpose the use of new biologic and non-biologic immunosuppressive agents, used to treat primary autoimmune disorders (AIDs), in the context of severe and/or steroid refractory irAE management. Depending on the immune-type predominant infiltrate, we propose a personalized treatment algorithm beyond corticosteroids. A shut-off strategy, intended to treat severe or steroid-refractory irAEs, based on the efficient inhibition of key inflammatory components involved in their pathophysiological processes, and limit potential adverse effects of drug immunosuppression on tumor response is proposed. This approach goes beyond current guidelines, challenging the step-by-step increase in drug immunosuppression proposed so far.