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Eur J Cancer. 2016 Jun;60:190-209. doi: 10.1016/j.ejca.2016.02.025. Epub 2016 Apr 13.

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

Author information

1
Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Germany.
2
Department of Dermatology, University Hospital Tübingen, Germany.
3
Department of Dermatology, University Hospital Mainz, Germany.
4
Department of Dermatology, University Hospital Zurich, Switzerland.
5
Department of Dermatology, University Hospital, University Duisburg-Essen, Germany.
6
Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Germany.
7
Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
8
Department of Dermatology, University Hospital Magdeburg, Germany.
9
Department of Dermatology, University Hospital Heidelberg, Germany.
10
Department of Dermatology, University Hospital Dresden, Germany.
11
Department of Dermatology and Allergology, Ludwig-Maximilian-University (LMU) Munich, Germany.
12
Department of Dermatology, University Hospital Münster, Münster, Germany.
13
Department of Dermatology, University Hospital RWTH Aachen, Germany.
14
Department of Dermatology, University Hospital Würzburg, Germany.
15
III. Medical Department, Technische Universität München (TUM), Munich, Germany.
16
Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Germany. Electronic address: Lucie.Heinzerling@uk-erlangen.de.

Abstract

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.

KEYWORDS:

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

PMID:
27085692
DOI:
10.1016/j.ejca.2016.02.025
[Indexed for MEDLINE]

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