NCMP-21 - Pembrolizumab-associated myositis, myasthenic crisis, and myocarditis in a patient with metastatic urothelial carcinoma

Although immune checkpoint inhibitors (ICIs) have improved systemic cancer care, in rare cases, patients develop neuromuscular immune related adverse events (irAEs), which carry high morbidity and mortality. This case study describes an 85-year-old male who developed the triad of myositis, myasthenic crisis, and myocarditis in association with ICI treatment for metastatic urothelial carcinoma (T3N0M1). The patient developed progressive weakness and gait impairment five weeks after initiating treatment with pembrolizumab. Later, he developed reduced ambulation, fatigue, shortness of breath, and orthopnea with concomitant ECG changes. Clinical exam demonstrated dysphagia, ptosis, proximal muscle weakness, fatigable weakness, and areflexia, ultimately resulting in respiratory failure, intubation, and inability to stand. Lab workup revealed elevated creatinine kinase, myoglobin, lactate dehydrogenase, and aldolase, but was notably negative for acetylcholine receptor and muscle specific kinase antibodies. Labs, clinical timeline, and clinical features supported his diagnoses. Interestingly, the cytokine panel demonstrated a high-normal soluble IL-2 receptor alpha which supports autoimmune pathology and elevated IL-10. 
The patient was treated with pyridostigmine, prednisone, and plasma exchange (PLEX) for 10 exchanges. EMG 10 days into treatment supported evidence of inflammatory myositis. After methylprednisone and PLEX treatment, the patient’s symptoms improved to ambulation with a walker and occasional BiPap support. His metastatic disease remained stable for several weeks while holding pembrolizumab due to toxicity. This case illustrates how early intervention and aggressive treatment for neuromuscular ICI-induced triad can stabilize patients and improve neurologic recovery. Due to the high morbidity and mortality for these irAEs, the authors support increased clinical scrutiny when evaluating these rare conditions and consideration of investigating the acute inflammatory processes. With improved pathophysiologic understanding of these rare conditions, the community can improve outcomes and refine treatments.