Stage IV ROS1-positive lung adenocarcinoma: entrectinib-associated ventricular tachyarrhythmia treated with plasma exchange

What happened, in summary

This 37-year-old Han Chinese man had Stage IV ROS1-positive lung adenocarcinoma and had started targeted therapy with entrectinib 600 mg once daily. Four days later, he came to the emergency department with sudden chest tightness and shortness of breath, followed by a 10-minute episode of coma. He arrived in shock, with tachycardia, severe hypotension, muffled heart sounds, and mottled skin. He also had a history of deep vein thrombosis managed with an inferior vena cava filter and rivaroxaban. ECG showed ventricular tachycardia with marked ST elevation in V1-V5, followed by polymorphic ventricular tachycardia. Lab testing showed mild troponin elevation and metabolic acidosis, with normal electrolytes. Despite cardioversion, amiodarone, lidocaine, beta-blockers, and vasopressors, the arrhythmia and hypotension persisted. Veno-arterial extracorporeal membrane oxygenation was started emergently to support circulation during the crisis. Coronary angiography showed no significant stenosis, and echocardiography showed diffuse ventricular hypokinesis with a left ventricular ejection fraction of 27%, without another structural explanation. Entrectinib was stopped after admission. The next day, therapeutic plasma exchange was initiated because the cardiac collapse was considered drug-related and refractory to standard measures. After plasma exchange, his rhythm returned to sinus rhythm, heart function recovered quickly, and VA-ECMO was successfully stopped on day 5. As of October 2025, he was discharged in improved condition on day 13. His course shows a rare but severe early cardiac toxicity after entrectinib, with recovery after drug discontinuation, VA-ECMO support, and therapeutic plasma exchange. Later lung-cancer response was not described, so the strongest documented outcome is recovery from the acute cardiotoxic event and continued oncology care.