title: The emerging toxicity profiles of anti-CTLA-4 antibodies across clinical indications.
abstract: The promising new class of immunomodulating antibodies directed against cytotoxic T-lymphocyte antigen-4 (CTLA-4) has been extensively tested in clinical trials and found to be active against cutaneous melanoma and other tumor histotypes. Inhibition of CTLA-4 characteristically induces well-identified side effects for which the definition "immune-related adverse events" (irAEs) has been proposed. IrAEs mainly include colitis/diarrhea, dermatitis, hepatitis, and endocrinopathies; uveitis, nephritis, and inflammatory myopathy also have been reported occasionally. These unique side effects are likely a direct result of breaking immune tolerance upon CTLA-4 blockade and are generally mild, reversible, and manageable, following specific treatment guidelines that include symptomatic therapies or systemic corticosteroids. However, patient-physician communication and early treatment are also emerging as critical issues to successfully manage irAEs, thus avoiding major complications. The major experience in identifying and managing CTLA-4 treatment-related side effects has derived from studies in melanoma patients; nevertheless, accumulating clinical experiences are clearly demonstrating that irAEs are class-specific events, and that they are fully overlapping in patients with tumors of different histotypes. This review provides an overview of current safety data on CTLA-4 antagonists and of available strategies to optimize their clinical use in cancer patients.
authors.affiliation: Department of Medical Oncology and Immunotherapy, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy. a.m.digiacomo@ao-siena.toscana.it
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Di Giacomo
authors.forename: Maurizio
authors.initials: M
authors.lastname: Biagioli
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000276:immunology*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D060908:CTLA-4 Antigen; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000628:therapy; D064420:Drug-Related Side Effects and Adverse Reactions; D004700:Endocrine System Diseases / Q000139:chemically induced / Q000276:immunology / Q000628:therapy; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000276:immunology / Q000628:therapy; D006801:Humans; D007154:Immune System Diseases / Q000139:chemically induced*; D000074324:Ipilimumab; D008545:Melanoma / Q000188:drug therapy; D012871:Skin Diseases / Q000139:chemically induced / Q000276:immunology / Q000628:therapy; D012878:Skin Neoplasms / Q000188:drug therapy
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D000074324:Ipilimumab; C520704:tremelimumab