title: Management of side effects of immune checkpoint blockade by anti-CTLA-4 and anti-PD-1 antibodies in metastatic melanoma.
abstract: CTLA-4 and PD-1 are potential targets for tumor-induced downregulation of lymphocytic immune responses. Immune checkpoint-modifying monoclonal antibodies oppose these effects, inducing T cell-mediated immune responses to various tumors including melanoma. Both anti-CTLA-4 and anti-PD-1 antibodies modify the interaction between tumor, antigen-presenting cells, and T lymphocytes. With respect to overall survival, clinical studies have shown a major benefit for the anti-CTLA-4 antibody ipilimumab as well as the two anti-PD-1 antibodies nivolumab and pembrolizumab. Following approval of ipilimumab in 2011, the latter two achieved market authorization in the summer of 2015. Immune responses thus induced and enhanced inevitably entail autoimmune phenomena, affecting various organs to varying degrees. Knowledge of these side effects is crucial with regard to prevention and management by treating physicians. Typically occurring early on and presenting with pronounced and persistent diarrhea, colitis represents a major and severe side effect. Other immune-mediated disorders include dermatitis, hypophysitis, thyroiditis, hepatitis, iridocyclitis as well as other less common autoimmune phenomena. Early recognition and initiation of treatment can reduce risks and sequelae for patients. This review describes the mechanisms of action of immune checkpoint blockade as well as its clinical effects in metastatic melanoma, with a detailed focus on the spectrum of adverse events and their therapeutic management.
authors.affiliation: Department of Dermatology, Venereology, and Allergology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Katharina C
authors.initials: KC
authors.lastname: Kähler
authors.affiliation: Department of Dermatology, and National Cancer Center, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Hassel
authors.affiliation: Department of Dermatology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Lucie
authors.initials: L
authors.lastname: Heinzerling
authors.affiliation: Department of Dermatology, Medical Faculty, University of Mainz, Mainz, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Loquai
authors.affiliation: Department of Dermatology, Venereology, and Allergology, University Medicine Göttingen, Göttingen, Germany.
authors.forename: Rotraut
authors.initials: R
authors.lastname: Mössner
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Hospital Essen, Essen, Germany.
authors.forename: Selma
authors.initials: S
authors.lastname: Ugurel
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Hospital Essen, Essen, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Zimmer
authors.affiliation: Hanover Skin Cancer Center, Department of Dermatology, Venereology, and Allergology, Hanover Medical College, Hanover, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gutzmer
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000628:therapy*; D006801:Humans; D000074324:Ipilimumab; D008545:Melanoma / Q000188:drug therapy*; D012878:Skin Neoplasms / Q000188:drug therapy*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; D000074324:Ipilimumab
keywords: CTLA-4 antibody; PD-1 antibody; autoimmune side effects; immune checkpoint blockade; melanoma; side effect management