(402) Pembrolizumab-Induced Myocarditis, Myositis, and Myasthenia Gravis

Introduction: Pembrolizumab is an immune checkpoint inhibitor widely used to treat various malignancies. However, rare immune-related adverse events (irAEs) have been reported with its use, including myocarditis, myositis, and myasthenia gravis (MG). This case report reviews a patient who experienced multiple adverse reactions following a single dose of pembrolizumab.

Description: A 79-year-old female with renal cell carcinoma, status-post right laparoscopic nephrectomy, received one dose of pembrolizumab to prevent disease recurrence. Four weeks later, she was admitted to the hospital with generalized weakness, dyspnea, and bilateral ptosis. Her troponin-I level was 11.13 ng/mL, and creatinine kinase (CK) was 2438 U/L. Cardiac catheterization revealed normal coronary arteries, while an echocardiogram showed mildly depressed left ventricular function. She developed severe hemodynamic instability with wide complex bradycardia, leading to a brief cardiac arrest and subsequent transvenous pacemaker placement. Due to worsening hypoxic respiratory failure, intubation was necessary. High-dose steroids (Solumedrol 1g IV) and IVIG (1g/kg) were administered for five days, improving her hemodynamics, troponin, and CK levels. Although tests for MG antibodies were negative, she continued to exhibit ptosis and weakness. After extubation to BiPAP, her hemodynamics and respiratory status deteriorated with the tapering of steroids. She received one dose of pyridostigmine but could not tolerate it due to bradycardia. Consequently, she was restarted on high-dose steroids and IVIG. Mycophenolate mofetil was added for additional immunosuppressive therapy. Despite treatment, she continued to experience repeated episodes of cardiac dysrhythmias and ultimately suffered another cardiac arrest, leading her family to choose comfort measures.

Discussion: Pembrolizumab-associated myocarditis, myositis, and MG represent rare and serious clinical presentations. Early recognition and prompt treatment are crucial. This case demonstrates the high fatality rate when a patient experiences multiple irAEs. Literature suggests that combination therapy with corticosteroids and IVIG can be effective in managing these conditions. Further research is needed to understand the mechanisms and risk factors associated with these adverse events.