Abstract Introduction Immune checkpoint inhibitors (ICI) are increasingly used to treat metastatic malignancies, particularly as advanced-line therapies. Intensivists frequently encounter patients receiving immunotherapy when they develop immune-related adverse events, or ICI-toxicities. One rare ICI-toxicity includes triple M overlap syndrome (TMOS), defined by the triad of myositis, myocarditis, and myasthenia gravis (MG). Case A 68-year-old male with metastatic anaplastic thyroid cancer (ATC) on dabrafenib/trametinib presented three weeks after his first pembrolizumab dose with neck weakness, dyspnea, dysphagia, and diplopia. Examination showed labored breathing, tachypnea, fatigable muscle weakness, and impaired neck flexion. Laboratory testing revealed elevated high-sensitivity troponin (1345 ng/L) and creatine kinase (2691 U/L). Venous blood gas demonstrated primary respiratory acidosis (pH 7.32, pCO2 56mmHg, bicarbonate 28.6mmol/L). Acetylcholine receptor antibodies were positive, and transthoracic echocardiogram demonstrated newly reduced left ventricular ejection fraction (34%). With biomarker evidence of myocarditis, myositis, and MG after recent ICI therapy, TMOS was diagnosed with oncology, neurology, and cardiology consultation. He was admitted to the ICU with hypercapnic respiratory failure requiring non-invasive ventilation (NIV). Multidisciplinary rounds occurred daily during his ICU stay. Given his poor oncologic prognosis and autoimmune complications, he declined intubation given contraindication to tracheostomy due to extensive tumor burden in his neck. He was started on high-dose methylprednisolone (1000 mg × 5 days) and intravenous immunoglobulin (2 g/kg x 4 days) on Day 1, and ruxolitinib (titrated to 15 mg) on Day 2. He also received abatacept (10 mg/kg, Day 1) and pyridostigmine (Day 5-6). He demonstrated clinical improvement on Day 6 and was weaned from NIV and transferred from the ICU on Day 10. He was discharged with nightly oxygen after electing hospice care. Discussion TMOS is an often fatal ICI-toxicity with in-hospital mortality up to 40%. The first report of TMOS due to pembrolizumab was only recently published. The patient presented with primary feature of neuromuscular weakness from MG, complicated by hypercapnic respiratory failure, though tracheostomy was not feasible given his malignancy. Expedited multidisciplinary discussions involving oncology, neurology, and cardiology, facilitated alignment of goals of care (GOC) with treatment planning, enabling selective use of novel therapies (abatacept and ruxolitib) and discharge from the ICU and transition to hospice. This case highlights the importance of multidisciplinary collaboration and increasing role of intensivists in managing ICI-toxicities in later-stage cancers. In such patients, a structured approach that emphasizes clarifying GOC within the context of advanced cancer, assessing treatment feasibility, and individualizing ICU management strategies is essential. This abstract is funded by: None
Sakuma et al. (Fri,) studied this question.