Myositis and neuromuscular side-effects induced by immune checkpoint inhibitors

Moreira, Alvaro; Loquai, Carmen; Pfoefer, Claudia; Kaehler, Katharina C.; Knauss, Samuel; Heppt, Markus V.; Gutzmer, Ralf; Dimitriou, Florentia; Meier, Friedegund; Mitzel-Rink, Heidrun; Schuler, Gerold; Terheyden, Patrick; Thoms, Kai-Martin; Tuerk, Matthias; Dummer, Reinhard; Zimmer, Lisa; Schröder, Rolf und Heinzerling, Lucie (2019): Myositis and neuromuscular side-effects induced by immune checkpoint inhibitors. In: European Journal of Cancer, Bd. 106: S. 12-23

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 antieprogrammed cell-death protein 1 (PD-1) antibodies and monitoring, which should include regular surveillance of creatine kinase. (C) 2018 Published by Elsevier Ltd.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0959-8049
• Sprache: Englisch