Title: Fatal cardiac arrhythmias secondary to pembrolizumab treatment
Introduction: Immunotherapy has revolutionized the treatment of cancer however vigilance regarding its adverse effects and multidisciplinary approach between oncology, cardiology and critical care can further improve outcomes.
Description: A 64-year-old female, with no preexisting cardiovascular disease, presented with dyspnea and was found to have heart rates of 110 bpm alternating with 50 bpm. Shortly afterwards she suffered a cardiac arrest due to ventricular fibrillation (VF) and was successfully defibrillated. The patient had a history of recurrent uterine serous carcinoma and had been initiated on pembrolizumab/lenvatinib three weeks earlier. Telemetry revealed 2:1 atrioventricular (AV) block and premature ventricular contractions (PVCs) with nonsustained ventricular tachycardia (VT). A transvenous pacer wire was placed emergently. Cardiac catheterization revealed angiographically normal coronary arteries. All chemotherapy drugs were held and she underwent implantable cardioverter-defibrillator (ICD) placement. Post-operatively, the patient suffered another VF cardiac arrest and was shocked out of it by the ICD. This was followed by another cardiac arrest due to pulseless electrical activity (PEA). After discussions with her family her code status was changed to comfort measures only.
Discussion: Pembrolizumab is an immune checkpoint inhibitor that works by blocking the PD-1 receptor on cell surfaces. 4-11% patients suffer from cardiac arrhythmias, esp. PVCs and VF. This may be a result of myocardial injury or by direct impact on electrical pathways. However, pembrolizumab may also cause AV blocks and other arrhythmias such as PEA and VT. Quick recognition and discontinuation of the offending agent is crucial. Our patient’s presentation was likely secondary to pembrolizumab however cancer itself can predispose to arrhythmias and the synergistic effects of lenvatinib and pembrolizumab on the heart are unclear. According to limited data available, onset of arrhythmias is typically within 2-4 weeks of treatment. Close outpatient monitoring and weekly testing of cardiac troponin and creatine kinase for the first 4 weeks of therapy may be beneficial. It is unclear if there are any predisposing factors to these adverse effects and further research may help oncologists risk stratify such patients.