title: Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination.
abstract: Inhibition of immune checkpoints using anti-programmed cell death-1 (PD-1) or anti cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibodies has revolutionized the management of patients with advanced-stage melanoma and is among the most promising treatment approaches for many other cancers. Use of CTLA-4 and PD-1 inhibitors, either as single agents, or in combination, has been approved by the US FDA for the treatment of metastatic melanoma. Treatment with these novel immunotherapies results in a unique and distinct spectrum of adverse events, which are mostly related to activation of the immune system and are, therefore, an unwanted consequence of their mechanisms of action. Adverse effects of CTLA-4 and/or PD-1 inhibition are most commonly observed in the skin, gastrointestinal tract, liver and endocrine systems and include pruritus, rash, nausea, diarrhoea and thyroid disorders. In this Review, the authors describe the adverse event profile of checkpoint inhibitors targeting CTLA-4 and PD-1, used both as monotherapies and in combination and aim to provide some general guidelines, based upon the mechanisms of action of these therapies and on the management of these immune-related adverse events.
authors.affiliation: Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Boutros
authors.affiliation: University of Pittsburgh, 4200 Fifth Avenue, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Tarhini
authors.affiliation: Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Routier
authors.affiliation: AP-HP, Internal Medicine Department, University Hospital of Bicêtre, 78 Rue du General Leclerc, 94270 Le Kremlin-Bicetre, France.|Paris Sud University, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicêtre, France.|INSERM Unit U1184, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicêtre, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambotte
authors.affiliation: Thoracic and Vascular Surgery Service, Centre Chirurgical Marie Lannelongue, 133 Avenue de la Resistance, 92350 Le Plessis-Robinson, France.
authors.forename: Francois Leroy
authors.initials: FL
authors.lastname: Ladurie
authors.affiliation: Paris Sud University, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicêtre, France.|AP-HP, Department of Gastroenterology, University Hospital of Bicêtre, Paris Sud University, 78 Rue du General Leclerc, 94270 Le Kremlin-Bicetre, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Carbonnel
authors.affiliation: Department of Nephrology, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'hopital, 75013 Paris, France.
authors.forename: Hassane
authors.initials: H
authors.lastname: Izzeddine
authors.affiliation: Drug Development Department (DITEP), Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
authors.forename: Aurelien
authors.initials: A
authors.lastname: Marabelle
authors.affiliation: INSERM Unit U981, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Champiat
authors.affiliation: Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
authors.forename: Armandine
authors.initials: A
authors.lastname: Berdelou
authors.affiliation: Biostatistic and Epidemiology Unit, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Lanoy
authors.affiliation: Biostatistic and Epidemiology Unit, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Texier
authors.affiliation: Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
authors.forename: Cristina
authors.initials: C
authors.lastname: Libenciuc
authors.affiliation: Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.|Paris Sud University, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicêtre, France.
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
authors.affiliation: Paris Sud University, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicêtre, France.|Drug Development Department (DITEP), Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.|INSERM Unit U981, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.affiliation: Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Mateus
authors.affiliation: Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.|Paris Sud University, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicêtre, France.|INSERM Unit U981, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Robert
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008213:Lymphocyte Activation / Q000276:immunology; D008545:Melanoma / Q000188:drug therapy*; D058990:Molecular Targeted Therapy / Q000379:methods; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology; D012878:Skin Neoplasms / Q000188:drug therapy*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor