Abstract 13651: Pembrolizumab Associated Myocarditis, Myasthenia Gravis, and Myositis

Abstract

Case: A 71 year old man presented with acute generalized muscle weakness, double vision, sagging eye lids, weakness with swallowing, shortness of breath, and dark urine. History was notable for stage IV non-small cell lung cancer with second dose of pembrolizumab therapy completed 12 days earlier. Exam showed bilateral ptosis and muffled speech. He had increased work of breathing, tachypnea, 3/5 strength in the bilateral lower extremities, and 5/5 strength in the upper extremities. His initial NIF was -25. Labs were notable for troponin of 1532, CK 16229, ESR 100, CRP 8.8, ALT 225, and AST 648. EKG revealed a new right bundle branch block and left posterior fascicular block. TTE showed EF of 65% without regional wall motion abnormalities. Cardiac MRI showed mildly elevated T1 and T2 relaxation times, suggestive of diffuse myocardial edema and inflammation without delayed gadolinium enhancement. He was treated with high dose steroids, fluid resuscitation, IVIG, and briefly pyridostigmine. On hospital day 8, he was found to have complete AV block with junctional escape rhythm. He had urgent placement of a temporary pacemaker. He was started on abatacept, ruxolitinib, and oral prednisone. Over the next 14 days he made gradual improvement. Discussion: While ICI-associated myocarditis is rare, it is worth investigating due to the high mortality. The clinical presentation can range from asymptomatic troponin elevations to cardiogenic shock and ventricular arrhythmias/AV block. Diagnosis requires a high index of suspicion and multiple diagnostic modalities, including ECG, echocardiography, serum biomarkers, and often cardiac MRI and endomyocardial biopsy. There is a large overlap between myocarditis and myositis. The mainstay treatments of ICI-induced myocarditis include holding the offending immune-checkpoint inhibitor, high-dose corticosteroids, and guideline-directed medical therapy for associated heart failure or arrhythmias. Abatacept, a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) immunoglobulin fusion protein, and ruxolitinib, a JAK 1/2 inhibitor, have recently been suggested as a novel combination to reduce mortality from ICI-associated myocarditis with concomitant myositis.