1. Myositis and neuromuscular side-effects induced by immune checkpoint inhibitors.
- Author
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Moreira A, Loquai C, Pföhler C, Kähler KC, Knauss S, Heppt MV, Gutzmer R, Dimitriou F, Meier F, Mitzel-Rink H, Schuler G, Terheyden P, Thoms KM, Türk M, Dummer R, Zimmer L, Schröder R, and Heinzerling L
- Subjects
- Adult, Aged, Aged, 80 and over, Databases, Factual, Female, Germany, Humans, Male, Middle Aged, Molecular Targeted Therapy adverse effects, Myositis diagnosis, Myositis immunology, Myositis therapy, Neoplasm Metastasis, Neuromuscular Diseases diagnosis, Neuromuscular Diseases immunology, Neuromuscular Diseases therapy, Registries, Retrospective Studies, Risk Assessment, Risk Factors, Skin Neoplasms immunology, Skin Neoplasms pathology, Switzerland, Time Factors, Young Adult, Antineoplastic Agents, Immunological adverse effects, Myositis chemically induced, Neuromuscular Diseases chemically induced, Skin Neoplasms drug therapy
- Abstract
Aim: To characterise clinical presentation, laboratory and histopathologic characteristics and assess the treatment and outcome of neuromuscular side-effects of checkpoint therapy., Methods: The side-effect registry and the institutional database from ten skin cancer centres were queried for reports on myositis and neuromuscular side-effects induced by checkpoint inhibitors. In total, 38 patients treated with ipilimumab, tremelimumab, nivolumab and pembrolizumab for metastatic skin cancer were evaluated and characterised., Results: Myositis was the most frequent neuromuscular adverse event. In 32% of cases, myositis was complicated by concomitant myocarditis. Furthermore, cases of isolated myocarditis, myasthenia gravis, polymyalgia rheumatica, radiculoneuropathy and asymptomatic creatine kinase elevation were reported. The onset of side-effects ranged from the first week of treatment to 115 weeks after the start of therapy. Most of the cases were severe (49% grade III-IV Common Terminology Criteria for Adverse Events), and there were two fatalities (5%) due to myositis and myositis with concomitant myocarditis. Only half of the cases (50%) completely resolved, whereas the rest was either ongoing or had sequelae. Steroids were given in 80% of the resolved cases and in 40% of the unresolved cases., Conclusion: Immune-mediated neuromuscular side-effects of checkpoint inhibitors greatly vary in presentation and differ from their idiopathic counterparts. These side-effects can be life threatening and may result in permanent sequelae. Occurrence of these side-effects must be taken into consideration for patient information, especially when considering adjuvant immunotherapy with anti-programmed cell-death protein 1 (PD-1) antibodies and monitoring, which should include regular surveillance of creatine kinase., (Copyright © 2018. Published by Elsevier Ltd.)
- Published
- 2019
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