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Hofmann, Lars; Forschner, Andrea; Loquai, Carmen; Goldinger, Simone M.; Zimmer, Lisa; Ugurel, Selma; Schmidgen, Maria I.; Gutzmer, Ralf; Utikal, Jochen S.; Göppner, Daniela; Hassel, Jessica C.; Meier, Friedegund; Tietze, Julia K.; Thomas, Ioannis; Weishaupt, Carsten; Leverkus, Martin; Wahl, Renate; Dietrich, Ursula; Garbe, Claus; Kirchberger, Michael C.; Eigentler, Thomas; Berking, Carola; Gesierich, Anja; Krackhardt, Angela M.; Schadendorf, Dirk; Schuler, Gerold; Dummer, Reinhard and Heinzerling, Lucie M. (2016): Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy. In: European Journal of Cancer, Vol. 60: pp. 190-209

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Background: Anti-programmed cell death receptor-1 (PD-1) antibodies represent an effective treatment option for metastatic melanoma as well as for other cancer entities. They act via blockade of the PD-1 receptor, an inhibitor of the T-cell effector mechanisms that limit immune responses against tumours. As reported for ipilimumab, the anti-PD-1 antibodies pembrolizumab and nivolumab can induce immune-related adverse events (irAEs). These side-effects affect skin, gastrointestinal tract, liver, endocrine system and other organ systems. Since life-threatening and fatal irAEs have been reported, adequate diagnosis and management are essential. Methods and findings: In total, 496 patients with metastatic melanoma from 15 skin cancer centers were treated with pembrolizumab or nivolumab;242 side-effects were described in 138 patients. In 116 of the 138 patients, side-effects affected the skin, gastrointestinal tract, liver, endocrine, and renal system. Rare side-effects included diabetes mellitus, lichen planus, and pancreas insufficiency due to pancreatitis. Conclusion: Anti-PD1 antibodies can induce a plethora of irAEs. The knowledge of them will allow prompt diagnosis and improve the management resulting in decreased morbidity. (C) 2016 Elsevier Ltd. All rights reserved.

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