Journal
EUROPEAN JOURNAL OF CANCER
Volume 60, Issue -, Pages 210-225Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2016.02.024
Keywords
Anti-PD-1; Side-effect; Toxicity; Pembrolizumab; Nivolumab; Checkpoint inhibitors; Tolerability; Immune-related; Adverse event
Categories
Funding
- University of Zurich
- Medac
- Roche
- MSD
- BMS
- Merck
- Novartis
- GSK
- Pfizer
- Amgen
- Almirall-Hermal
- LEO
- Galderma
- Janssen
- Boehringer-Ingelheim
- JohnsonJohnson
- Boehringer Ingelheim
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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. (C) 2016 Published by Elsevier Ltd.
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