Myositis and Neuromuscular Side-Effects Induced by Immune Checkpoint Inhibitors

Eur J Cancer. 2019 Jan;106:12-23. doi: 10.1016/j.ejca.2018.09.033. Epub 2018 Nov 17.

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.

Keywords: Immune checkpoint inhibitors; Myositis; Neuromuscular side effects; Tocilizumab.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / adverse effects*
  • Databases, Factual
  • Female
  • Germany
  • Humans
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / adverse effects
  • Myositis / chemically induced*
  • Myositis / diagnosis
  • Myositis / immunology
  • Myositis / therapy
  • Neoplasm Metastasis
  • Neuromuscular Diseases / chemically induced*
  • Neuromuscular Diseases / diagnosis
  • Neuromuscular Diseases / immunology
  • Neuromuscular Diseases / therapy
  • Registries
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology
  • Switzerland
  • Time Factors
  • Young Adult

Substances

  • Antineoplastic Agents, Immunological