Journal article
Myositis and neuromuscular side-effects induced by immune checkpoint inhibitors.
- Moreira A Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Germany.
- Loquai C Department of Dermatology, University Hospital of Mainz, Mainz, Germany.
- Pföhler C Department of Dermatology, Saarland University Medical School, Homburg, Germany.
- Kähler KC Department of Dermatology, Skin Cancer Center, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel, Germany.
- Knauss S Department of Experimental Neurology, Charité Universitätsmedizin Berlin, Germany.
- Heppt MV Department of Dermatology and Allergy, University Hospital, LMU Munich, Frauenlobstr. 9-11, 80337 Munich, Germany.
- Gutzmer R Skin Cancer Center Hannover, Department of Dermatology and Allergy, Hannover Medical School, Germany.
- Dimitriou F Department of Dermatology, University Hospital Zurich, Switzerland.
- Meier F Department of Dermatology, University Hospital Dresden, Germany.
- Mitzel-Rink H Department of Dermatology, University Hospital of Mainz, Mainz, Germany.
- Schuler G Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Germany.
- Terheyden P Department of Dermatology, University of Lübeck, Lübeck, Germany.
- Thoms KM Department of Dermatology, University Hospital Göttingen, Germany.
- Türk M Department of Neuropathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Germany.
- Dummer R Department of Dermatology, University Hospital Zurich, Switzerland.
- Zimmer L Department of Dermatology, University Duisburg-Essen, Germany.
- Schröder R Department of Neuropathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Germany.
- Heinzerling L Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Germany. Electronic address: Lucie.Heinzerling@uk-erlangen.de.
- 2018-11-20
Published in:
- European journal of cancer (Oxford, England : 1990). - 2019
Immune checkpoint inhibitors
Myositis
Neuromuscular side effects
Tocilizumab
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Immunological
Databases, Factual
Female
Germany
Humans
Male
Middle Aged
Molecular Targeted Therapy
Myositis
Neoplasm Metastasis
Neuromuscular Diseases
Registries
Retrospective Studies
Risk Assessment
Risk Factors
Skin Neoplasms
Switzerland
Time Factors
Young Adult
English
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.
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.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1016/j.ejca.2018.09.033
- PMID 30453170
- Persistent URL
- https://susi.usi.ch/global/documents/266950
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