(918) Pembrolizumab-Induced Triple-M (Myocarditis-Myositis-Myasthenia Gravis) Syndrome

Introduction: Pembrolizumab is a programmed cell death protein 1 (PD-1) immune checkpoint inhibitor with demonstrated significant efficacy in various solid tumors. Although overall well tolerated, several immune related adverse events (irAEs) associated with its use have been reported. We describe a case of pembrolizumab-induced myositis and myasthenia gravis, further complicated by myocarditis resulting in complete heart block (CHB) requiring a permanent pacemaker.

Description: A 79-year-old male with stage IV non-small cell lung cancer (NSCLC) treated with pembrolizumab presented with worsening dyspnea. Physical exam was remarkable for right ptosis. He was afebrile and hemodynamically stable. Chest radiograph showed chronic airspace opacities. Laboratory data revealed elevated troponin-I (10.46 ng/mL) and creatine kinase of 2502 U/L. ECG showed third-degree AV block, new-onset LBBB and ST-T abnormalities. Echocardiogram revealed normal LV function (EF 75%). Respiratory viral panel and COVID-19 PCR were negative. Given suspicion for acute coronary syndrome, he received aspirin and heparin infusion and admitted to the ICU. The clinical, laboratory and ECG abnormalities were attributed to pembrolizumab after a multidisciplinary discussion. Heparin infusion was discontinued and 1g methylprednisolone and 10 mg/kg abatacept x 3 days were given for myocarditis, and immune globulin x 5 days for the concurrent MG. Cardiac MRI showed features of myocardial inflammation. A transvenous pacemaker was placed for the CHB and transitioned to a leadless pacemaker due to the persistent pacing requirement on hospital day 7. Subsequent coronary angiogram showed stable coronary disease. Endomyocardial biopsy did not yield sufficient tissue for diagnosis. He remained hemodynamically stable and was discharged home on a steroid taper. On outpatient follow-up 10 days later, he remained stable with chemotherapy on hold pending further evaluation of thrombocytopenia.

Discussion: The co-occurrence of pembrolizumab-induced myositis, MG and myocarditis in a patient with NSCLC is extremely rare. The exact pathogenesis of myocarditis and conduction abnormalities in this setting is poorly understood. Rapid diagnosis, close monitoring, multidisciplinary collaboration, and treatment with steroids is key to optimize patient outcomes.