Myositis and neuromuscular side-effects induced by immune checkpoint inhibitors

Alvaro Moreira, Carmen Loquai, Claudia Pföhler, Katharina C. Kähler, Samuel Knauss, Markus V. Heppt, Ralf Gutzmer, Florentia Dimitriou, Friedegund Meier, Heidrun Mitzel-Rink, Gerold Schuler, Patrick Terheyden, Kai Martin Thoms, Matthias Türk, Reinhard Dummer, Lisa Zimmer, Rolf Schröder, Lucie Heinzerling*

*Corresponding author for this work
54 Citations (Scopus)


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.

Original languageEnglish
JournalEuropean Journal of Cancer
Pages (from-to)12-23
Number of pages12
Publication statusPublished - 01.2019

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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