A Unique Case of Pembrolizumab-Induced Unilateral Chylothorax in the Absence of Capillary Leak Syndrome

Abstract Introduction: Myriad adverse events – and specifically immune-related adverse events – affecting any organ system are known risks of immune checkpoint inhibitors (ICI). There are rare reports of ICI-related chylothorax and capillary leak syndrome. Presented is a unique case of recurrent right chylothorax without systemic capillary leak syndrome in a patient treated with pembrolizumab for stage IIIb malignant melanoma of the back. Case Report: A 56 year old female with malignant melanoma complicated by pembrolizumab-associated ITP and aplastic anemia presented with dyspnea and hypoxia. Her last dose of pembrolizumab was 5 months prior to presentation. She presents in mild respiratory distress but normotensive and without peripheral edema. Chest x-ray was revealing for a large right pleural effusion. Fluid studies demonstrated chylothorax without malignant cells. PET scan showed no increased pleural or parenchymal uptake. After 48 hours of percutaneous chest tube drainage followed by talc pleurodesis, the patient was discharged on a very low-fat diet and octreotide. The patient returned three weeks later with worsening dyspnea and productive cough. Imaging revealed reaccumulating right pleural effusion and a new small left sided pleural effusion. Patient underwent right video-assisted thoracoscopic surgery which revealed no discernible surgical or anatomical evidence of chylous leakage or thoracic duct dysfunction despite instillation of heavy cream, no malignancy from diaphragmatic biopsies, and persistent chylothorax. A chest tube was placed followed by repeat talc pleurodesis, and the thoracic duct was ligated. Left sided thoracentesis revealed an exudative effusion with no malignant cells. The patient was diagnosed with lymphatic capillary dysfunction secondary to pembrolizumab with concern for impending capillary leak syndrome in the setting of post-operative hypotension, however she did not develop any additional hallmark symptoms such as generalized edema, hypoalbuminemia, or persistent hypotension. She was treated with 5 days of IVIG, a prolonged steroid taper, and octreotide and had significant improvement in her oxygenation and dyspnea over the next several days. Small bilateral effusions were stable for 1 year, however she then reaccumulated a large left exudative effusion with normal triglycerides and still no evidence of malignancy. Discussion: This is a unique case on the spectrum of lymphatic disruption secondary to ICI given unilaterality of the chylothorax as well as absence of additional findings consistent with a fulminant capillary leak syndrome.