Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy

Lars Hofmann, Andrea Forschner, Carmen Loquai, Simone M. Goldinger, Lisa Zimmer, Selma Ugurel, Maria I. Schmidgen, Ralf Gutzmer, Jochen S. Utikal, Daniela Göppner, Jessica C. Hassel, Friedegund Meier, Julia K. Tietze, Ioannis Thomas, Carsten Weishaupt, Martin Leverkus, Renate Wahl, Ursula Dietrich, Claus Garbe, Michael C. KirchbergerThomas Eigentler, Carola Berking, Anja Gesierich, Angela M. Krackhardt, Dirk Schadendorf, Gerold Schuler, Reinhard Dummer, Lucie M. Heinzerling

Research output: Contribution to journalArticlepeer-review

516 Scopus citations


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.

Original languageEnglish
Pages (from-to)190-209
Number of pages20
JournalEuropean Journal of Cancer
StatePublished - 1 Jun 2016


  • Adverse event
  • Anti-PD-1
  • Checkpoint inhibitors
  • Immune-related
  • Nivolumab
  • Pembrolizumab
  • Side-effect
  • Tolerability
  • Toxicity


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