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Background: Myositis is a rare immune checkpoint inhibitor (ICI)-related adverse event frequently associated with myasthenia gravis (MG) and myocarditis (MC) leading to mortality rates up to 52%. 1
Objectives: To characterize the presentation, course and outcomes of patients with ICI-related myositis alone or with overlap syndrome (myositis with MG or MC or both).
Methods: We retrospectively identified a cohort of patients treated with ICI at MD Anderson Cancer Center between 2016 and 2019. Suspected myositis was identified using International Classification of Disease version 10 codes and confirmed by electronic medical record review of muscle enzymes, pathology, and other tests, when available. Patients with myositis alone or with overlap syndrome were compared using Fischer’s exact tests and t tests.
Results: During the study period 8,636 patients received ICI, of which 31 (0.36%) were diagnosed with myositis: 14 (45%) with myositis alone and 17 (55%) with overlap (MG in 5, MC in 4, MG and MC in 8). Twenty patients received programmed death-1 (PD-1) or programmed death-ligand-1 (PDL-1) inhibitors, and 10 received combination PD-1/PDL-1 inhibitor with a cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) inhibitor. One patient received single agent CTLA-4 inhibitor (excluded from pooled data). For the entire cohort the median age at diagnosis was 69 years (range: 40-95 years); the most common presenting symptoms were fatigue in 27 (90%) patients, weakness in 24 (80%), and myalgia in 23 (77%); median CK was 2,236 U/L (range: 23-19,794 U/L). For treatment, 22 of 30 (73%) patients received at least one therapy in addition to steroids: plasmapheresis in 15 (50%) patients, intravenous immune globulin (IVIG) in 12 (40%), biologics in 9 (30%) (rituximab in 6, infliximab in 5, tocilizumab in 3), tacrolimus in 6 (20%), and mycophenolate mofetil in 4 (13%). Median length of exposure to steroids was 47 days (range: 1-250 days). Five (17%) patients were rechallenged with ICI after myositis resolution (3 with myositis alone, 2 with overlap), of which 1 (20%) patient experienced a myositis flare. Twenty-five (83%) patients were not rechallenged on ICI and 3 (12%) of those patients had a flare. Differences between patients with myositis alone compared to those with overlap are shown in
Myositis alone vs. Overlap
| Myositis alone (N=13) |
Overlap
| P value | |
|---|---|---|---|
| N(%)/median days [range] | |||
| Time to symptom onset | 42 [10-161] | 22 [9-149] | 0.234 |
| Initial steroid dose (mg/kg day) | 1.7 | 1.8 | 0.187 |
| Second therapy | 7 (54) | 15 (88) | 0.049 |
| Plasmapheresis | 3 (23) | 12 (71) | 0.025 |
| IVIG | 1 (8) | 11 (65) | 0.002 |
| Outcomes | |||
| Hospitalization length | 5 [2-50] | 24 [7-92] | 0.019 |
| Respiratory failure | 0 (0) | 13 (76) | |
| Symptoms at discharge | 0.047 | ||
| Improved | 8 (62) | 6 (35) | |
| Resolved | 3 (23) | 1 (6) | |
| Death | |||
| Overall | 8 (62) | 12 (71) | 0.706 |
| Adverse event | 0 (0) | 7 (41) | |
Conclusion: Our results represent the largest cohort of ICI-related myositis to date. Patients with overlap syndrome are treated more aggressively and have worse outcomes than those with myositis alone. Prospective studies are warranted to determine risk factors for developing myositis or overlap syndrome and to determine optimal treatment.
REFERENCES:
[1]Anquetil BC, Salem LJ-E, Lebrun-Vignes JB, et al. Immune Checkpoint Inhibitor–Associated Myositis: Expanding the Spectrum of Cardiac Complications of the Immunotherapy Revolution. Circulation . 2018;138(7):743-745.
Disclosure of Interests: None declared