Abstract
Imatinib, a tyrosine kinase inhibitor, is widely used for treating gastrointestinal stromal tumors (GISTs) and chronic myeloid leukemia (CML). While commonly associated with mild fluid retention, significant pleural effusion is an uncommon but potentially serious adverse effect. We present a case of recurrent pleural effusions secondary to imatinib therapy in a 62-year-old female patient with metastatic lung adenocarcinoma and a concurrent GIST harboring an exon 9 mutation. She was initiated on imatinib 400 mg daily, later increased to twice daily. Within weeks, she developed progressive dyspnea, and imaging revealed large bilateral pleural effusions. Pleural fluid analysis demonstrated an exudative effusion, with cytology and microbiological studies ruling out infection or malignancy. Cardiac function was preserved, and there were no signs of volume overload. She underwent multiple thoracenteses for symptomatic relief. Due to recurrent pleural effusions, imatinib was permanently discontinued, leading to complete resolution of the effusions. Subsequent treatment with sunitinib was not tolerated due to severe mucositis and cytopenias. Despite discontinuation of targeted therapy, both her GIST and metastatic lung cancer remained stable under surveillance. While pleural effusions are frequently reported with dasatinib, they are rare with imatinib. The proposed mechanisms include inhibition of platelet-derived growth factor receptors (PDGFRs), leading to increased vascular permeability, impaired lymphatic drainage, and renal sodium retention. Dose reduction may mitigate fluid retention; however, our patient developed significant pleural effusions at standard dosing, necessitating treatment discontinuation. This case underscores the importance of recognizing pleural effusion as a rare but serious adverse effect of imatinib therapy. Clinicians should maintain a high index of suspicion for drug-induced pleural effusions, particularly in the absence of other etiologies, and consider discontinuation if clinically indicated. Early recognition and management can prevent complications and improve patient outcomes.