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

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.

• Authors: Lisa Zimmer, Simone M Goldinger, Lars Hofmann, Carmen Loquai, Selma Ugurel, Ioannis Thomas, Maria I Schmidgen, Ralf Gutzmer, Jochen S Utikal, Daniela Göppner, Jessica C Hassel, Friedegund Meier, Julia K Tietze, Andrea Forschner, Carsten Weishaupt, Martin Leverkus, Renate Wahl, Ursula Dietrich, Claus Garbe, Michael C Kirchberger, Thomas Eigentler, Carola Berking, Anja Gesierich, Angela M Krackhardt, Dirk Schadendorf, Gerold Schuler, Reinhard Dummer, Lucie M Heinzerling
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 60 Pg. 210-25 (06 2016) ISSN: 1879-0852 [Electronic] England
• PMID: 27084345 (Publication Type: Journal Article, Multicenter Study)
• Copyright: Copyright © 2016. Published by Elsevier Ltd.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Ipilimumab
• Programmed Cell Death 1 Receptor
• Nivolumab
• pembrolizumab

Topics

• Adult
• Aged
• Antibodies, Monoclonal (adverse effects)
• Antibodies, Monoclonal, Humanized (adverse effects)
• Antineoplastic Agents (adverse effects)
• Cell Cycle Checkpoints
• Eye Diseases (chemically induced)
• Female
• Heart Diseases (chemically induced)
• Humans
• Ipilimumab
• Male
• Melanoma (drug therapy)
• Middle Aged
• Musculoskeletal Diseases (chemically induced)
• Nervous System Diseases (chemically induced)
• Nivolumab
• Programmed Cell Death 1 Receptor (antagonists & inhibitors)
• Respiratory Tract Diseases (chemically induced)
• Retrospective Studies
• Skin Neoplasms (drug therapy)