Myositis and neuromuscular side-effects induced by immune checkpoint inhibitors

Moreira A, Loquai C, Pfoefer C, Kaehler 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, Heinzerling L (2019)


Publication Type: Journal article

Publication year: 2019

Journal

Book Volume: 106

Pages Range: 12-23

DOI: 10.1016/j.ejca.2018.09.033

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.

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APA:

Moreira, A., Loquai, C., Pfoefer, C., Kaehler, K.C., Knauss, S., Heppt, M.V.,... Heinzerling, L. (2019). Myositis and neuromuscular side-effects induced by immune checkpoint inhibitors. European Journal of Cancer, 106, 12-23. https://dx.doi.org/10.1016/j.ejca.2018.09.033

MLA:

Moreira, Alvaro, et al. "Myositis and neuromuscular side-effects induced by immune checkpoint inhibitors." European Journal of Cancer 106 (2019): 12-23.

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