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.
| Original language | English |
|---|---|
| Journal | European Journal of Cancer |
| Volume | 106 |
| Pages (from-to) | 12-23 |
| Number of pages | 12 |
| ISSN | 0959-8049 |
| DOIs | |
| Publication status | Published - 01.2019 |
Funding
Carmen Loquai is an advisory board member, received speaker's fee and travel reimbursement from BMS, MSD, Novartis, Roche, Amgen, Pierre Fabre, Sun Pharma and Idera outside the submitted work. Claudia Pföhler received honoraria from Novartis, BMS, GSK, MSD, Roche, Amgen and Merck Serono; is a consultor or advisor for Novartis, Amgen, Roche and Merck Serono and received travel reimbursement from Novartis, GSK, MSD, BMS, Amgen, Roche and Merck Serono outside the submitted work. Katharina C. Kähler received consultant fees from Roche, BMS and MSD and travel reimbursement and speaker fees from Roche, BMS, MSD and Amgen outside the submitted work. Markus V. Heppt received speaker's fee from Roche, Novartis, BMS and MSD and travel reimbursement from BMS outside the submitted work. Ralf Gutzmer received research support from Pfizer, Johnson & Johnson and Novartis; honoraria for lectures from Roche Pharma, Bristol-Myers Squibb, GlaxoSmithKline, Novartis, MSD, Almirall-Hermal, Amgen, Boehringer Ingelheim and AstraZeneca and cover letter honoraria for advice from Roche Pharma, Bristol-Myers Squibb, GlaxoSmithKline, Novartis, MSD, Almirall-Hermal, Amgen, LEO, Pierre Fabre, Merck Serono, 4SC and Incyte outside the submitted work. Friedegund Meier received honoraria from GSK/Novartis, Roche, BMS, MSD and Amgen; is a consultor or advisor from GSK/Novartis, Roche and BMS; received research funding from Novartis and received travel reimbursement from Novartis, Roche, BMS and MSD outside the submitted work. Patrick Terheyden received honoraria from Roche, BMS, Merck and Amgen; is a consultor or advisor for BMS, Roche, Merck and Novartis and received travel reimbursement from BMS, Merck and Roche outside the submitted work. Reinhard Dummer has project-focussed consulting and/or advisory relationships with Novartis, MSD, BMS, Roche, Amgen, Takeda and Pierre Fabre outside the submitted work. Lisa Zimmer received honoraria from Roche outside the submitted work. Lucie Heinzerling received consultancy fees, speaker's fees and travel grants from, and is an advisory board member of BMS, MSD, Roche, Amgen, Curevac and Novartis outside the submitted work. The other authors declare that they have no conflict of interest to disclose.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
