Alvaro Moreira1, Carmen Loquai2, Claudia Pföhler3, Katharina C Kähler4, Samuel Knauss5, Markus V Heppt6, Ralf Gutzmer7, Florentia Dimitriou8, Friedegund Meier9, Heidrun Mitzel-Rink2, Gerold Schuler1, Patrick Terheyden10, Kai-Martin Thoms11, Matthias Türk12, Reinhard Dummer8, Lisa Zimmer13, Rolf Schröder12, Lucie Heinzerling14. 1. Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Germany. 2. Department of Dermatology, University Hospital of Mainz, Mainz, Germany. 3. Department of Dermatology, Saarland University Medical School, Homburg, Germany. 4. Department of Dermatology, Skin Cancer Center, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel, Germany. 5. Department of Experimental Neurology, Charité Universitätsmedizin Berlin, Germany. 6. Department of Dermatology and Allergy, University Hospital, LMU Munich, Frauenlobstr. 9-11, 80337 Munich, Germany. 7. Skin Cancer Center Hannover, Department of Dermatology and Allergy, Hannover Medical School, Germany. 8. Department of Dermatology, University Hospital Zurich, Switzerland. 9. Department of Dermatology, University Hospital Dresden, Germany. 10. Department of Dermatology, University of Lübeck, Lübeck, Germany. 11. Department of Dermatology, University Hospital Göttingen, Germany. 12. Department of Neuropathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Germany. 13. Department of Dermatology, University Duisburg-Essen, Germany. 14. Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Germany. Electronic address: Lucie.Heinzerling@uk-erlangen.de.
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.
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.
Authors: Karmela Kim Chan; Cynthia Magro; Alexander Shoushtari; Charles Rudin; Veronica Rotemberg; Anthony Rossi; Cecilia Lezcano; John Carrino; David Fernandez; Michael A Postow; Arlyn Apollo; Mario E Lacouture; Anne R Bass Journal: Oncologist Date: 2019-10-15
Authors: Marije S Koks; Gurbey Ocak; Britt B M Suelmann; Cornelia A R Hulsbergen-Veelken; Saskia Haitjema; Marieke E Vianen; Marianne C Verhaar; Karin A H Kaasjager; Meriem Khairoun Journal: PLoS One Date: 2021-06-08 Impact factor: 3.240
Authors: Julie R Brahmer; Hamzah Abu-Sbeih; Paolo Antonio Ascierto; Jill Brufsky; Laura C Cappelli; Frank B Cortazar; David E Gerber; Lamya Hamad; Eric Hansen; Douglas B Johnson; Mario E Lacouture; Gregory A Masters; Jarushka Naidoo; Michele Nanni; Miguel-Angel Perales; Igor Puzanov; Bianca D Santomasso; Satish P Shanbhag; Rajeev Sharma; Dimitra Skondra; Jeffrey A Sosman; Michelle Turner; Marc S Ernstoff Journal: J Immunother Cancer Date: 2021-06 Impact factor: 13.751