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Cardiac Tamponade in a Patient with Stage IV Lung Adenocarcinoma Treated with Pembrolizumab

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Background: In 2018, a male aged 62 years with a history of squamous cell tonsillar cancer, which was successfully treated by concurrent chemoradiation and selective neck dissection in 2014, was diagnosed with primary right sided lung adenocarcinoma (Stage IV, cT4c cN3 cM1a) after presenting with post-obstructive pneumonia. Molecular analysis was about 100% positive for PDL-1 and negative for EGFR, ALK, BRAF, and ROS. The patient was started on Pembrolizumab. After 5 cycles, he developed worsening dyspnea. A CT scan of his chest revealed a large pericardial effusion and decrease in size of right upper lobe lesion. An echocardiogram confirmed cardiac tamponade physiology. 400 ml of fluid was removed by emergent pericardial window and surgical drain was placed. Cytopathological analysis of pericardial fluid returned negative for malignant cells. The patient was treated with high dose prednisone with tapering, and pembrolizumab was discontinued. Patient responded very well. A repeat CT and ECHO after 3 months of treatment confirmed nearresolution of effusion.

Discussion: Distinguishing immune mediated pericardial effusion from malignant effusion is vital. Development of pericardial effusion with concurrent improvement or stability of malignant lesion, negative cytology and brisk response to corticosteroids indicates an immune etiology.

Pericardiocentesis or pericardial window is the key intervention in acute management. The critical step in immune mediated pericardial effusions is initiation of high-dose corticosteroids (1-2 mg/kg of Prednisone) with tapering of at least 4 weeks in severe cases. In unresponsive cases, corticosteroids at transplant rejection dose (1 g methylprednisone daily) and addition of mycophenolate mofetil, in iximab or antithymocyte globulin should be considered. As per ‘ASCO Practice Guideline’, any grade of cardiotoxicity above grade 1 warrants holding or permanently discontinuing the immunotherapy. For pericardial effusions secondary to pseudoprogression, immunotherapy can be continued.

Based on our literature review, concurrence of other immune related adverse events and recurrence of effusions with discontinuation of corticosteroids is reported with immune mediated pericardial effusions.

Conclusion: Early identification of immune related adverse events is very important. In immune mediated pericardial effusion, pericardial fluid should be drained, and corticosteroids should be started promptly. Permanent discontinuation of immunotherapy is recommended for grade 3 and 4 cardiotoxicity. Re-challenge of immunotherapy after treating the adverse event is a subject that needs further research.

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