Abstract T-cell dysregulation caused by immune checkpoint inhibitors (ICIs) can lead to a rare and often fatal overlap syndrome consisting of myositis, myocarditis, and myasthenia gravis (IM3OS). We present a case of IM3OS following combination ICI therapy for melanoma. A 71-year-old male with melanoma, status post 2 cycles of ipilimumab and nivolumab, presented with myalgias, proximal muscle weakness, dysarthria, encephalopathy, and hypercapnic respiratory failure requiring intubation. Workup revealed a troponin of 10,000 ng/L, diffuse ST-segment depressions, preserved left ventricular function without regional wall motion abnormalities, and a non-obstructive cardiac catheterization. Additional findings included creatine kinase (CK) of 4,000 U/L, negative aldolase, positive acetylcholine receptor (AChR) antibodies, negative muscle-specific kinase (MuSK) antibodies, and electromyography (EMG) with myopathic pattern. These findings raised concern for ICI-induced IM3OS. High dose methylprednisolone (1g/day) and intravenous immunoglobulin (IVIG) were initiated for 5 days with symptomatic and laboratory improvement. Rituximab was considered but deferred given unclear additional benefit. The patient subsequently underwent tracheostomy with plans for discharge to long-term care facility for ventilator weaning. However, his course was complicated by recurrent infections and hemodynamic instability, after which goals of care were redirected toward comfort. ICIs block inhibitory pathways exploited by cancer cells to evade immune detection. However, this can lead to T-cell dysregulation and molecular mimicry against shared antigens within the skeletal muscle, myocardium, and neuromuscular junction, resulting in this rare overlap syndrome. IM3OS carries a high in-hospital mortality rate of 60% and an incidence of less than 1% in ICI-treated patients. Symptoms typically arise after 1-2 ICI doses. Neuromuscular symptoms often precede cardiac involvement. Combination ICI therapy has a threefold higher incidence of inflammatory myopathies than monotherapy, and an earlier onset of symptoms. Diagnostic workup includes CK, aldolase, and myositis panel if concurrent myositis is suspected, as well as a cardiac MRI typically showing late subepicardial gadolinium enhancement and endomyocardial biopsy with lymphocytic infiltration and myocyte injury. AChR and MuSK autoantibodies are often detected, but seronegative myasthenia gravis can occur. Data on optimal treatment is limited, but includes high dose steroids, and IVIG or plasmapheresis. Immunosuppressants such as rituximab or mycophenolate are considered in steroid-refractory cases. Emerging data suggests a link between IM3OS and striational antibodies, which could be utilized as biomarkers for early detection. This case illustrates the rarity, high mortality, and therapeutic challenges surrounding IM3OS, highlighting the need for early recognition and prompt treatment. Further investigation is warranted to optimize treatment strategies and improve outcomes. This abstract is funded by: None
Salman et al. (Fri,) studied this question.