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Eur J Cancer. 2016 Jun;60:210-25. doi: 10.1016/j.ejca.2016.02.024. Epub 2016 Apr 13.

Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy.

Author information

1
Department of Dermatology, University Hospital, University Duisburg-Essen, Germany.
2
Department of Dermatology, University Hospital Zurich, Switzerland.
3
Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Germany.
4
Department of Dermatology, University Hospital Mainz, Germany.
5
Department of Dermatology, University Hospital Tübingen, 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, University Hospital Munich (LMU), Germany.
12
Department of Dermatology, University Hospital 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 1 (PD-1) antibodies represent an effective treatment option for metastatic melanoma and 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 can involve skin, gastrointestinal tract, liver, the 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 centres were treated with pembrolizumab or nivolumab. Two hundred forty two side-effects in 138 patients have been analysed. In 77 of the 138 patients side-effects affected the nervous system, respiratory tract, musculoskeletal system, heart, blood and eyes. Not yet reported side-effects such as meningo-(radiculitis), polyradiculitis, cardiac arrhythmia, asystolia, and paresis have been observed. Rare and difficult to manage side-effects such as myasthenia gravis are described in detail.

CONCLUSION:

Anti-PD-1 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:
27084345
DOI:
10.1016/j.ejca.2016.02.024
[Indexed for MEDLINE]

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