title: Management of toxicities of immune checkpoint inhibitors.
abstract: Immune checkpoint inhibition with the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibodies nivolumab and pembrolizumab has improved survival in metastatic melanoma, lung cancer and renal cancer. Use of these agents holds promise in other malignancies. The augmented immune response enabled by these agents has led to a particular group of side effects called immune-related adverse events (irAEs). The main irAEs include diarrhea, colitis, hepatitis, skin toxicities and endocrinopathies such as hypophysitis and thyroid dysfunction. The anti-PD-1 antibodies have a different toxicity profile to ipilimumab with fewer high grade events. This article identifies the rates of common and uncommon irAEs associated with each immune checkpoint inhibitor (ICPI) and their timing of onset, focusing mainly on the experience in melanoma and lung cancer. An approach to management for each class of irAE is provided.
authors.affiliation: Melanoma Unit, Royal Marsden Foundation Trust, Fulham Road, London SW3 6JJ, United Kingdom.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Spain
authors.affiliation: Melanoma Unit, Royal Marsden Foundation Trust, Fulham Road, London SW3 6JJ, United Kingdom.
authors.forename: Stefan
authors.initials: S
authors.lastname: Diem
authors.affiliation: Melanoma Unit, Royal Marsden Foundation Trust, Fulham Road, London SW3 6JJ, United Kingdom. Electronic address: james.larkin@rmh.nhs.uk.
authors.forename: James
authors.initials: J
authors.lastname: Larkin
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D002292:Carcinoma, Renal Cell / Q000188:drug therapy; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000209:etiology*; D003092:Colitis / Q000139:chemically induced* / Q000188:drug therapy; D016572:Cyclosporine / Q000627:therapeutic use; D003967:Diarrhea / Q000139:chemically induced* / Q000188:drug therapy; D003875:Drug Eruptions / Q000188:drug therapy / Q000209:etiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000069285:Infliximab / Q000627:therapeutic use; D000074324:Ipilimumab; D007680:Kidney Neoplasms / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D008545:Melanoma / Q000188:drug therapy; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy*; D000077594:Nivolumab; D010900:Pituitary Diseases / Q000139:chemically induced* / Q000188:drug therapy; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D012878:Skin Neoplasms / Q000188:drug therapy; D016559:Tacrolimus / Q000627:therapeutic use; D013966:Thyroiditis / Q000139:chemically induced* / Q000188:drug therapy
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; D007166:Immunosuppressive Agents; D000074324:Ipilimumab; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; D016572:Cyclosporine; D000069285:Infliximab; C582435:pembrolizumab; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: Immune-checkpoint inhibitors; Immune-related adverse events; Ipilimumab; Lung cancer; Melanoma; Nivolumab; Pembrolizumab; Renal cancer