Pralsetinib-Induced Interstitial Pneumonitis in a Patient with Metastatic Pulmonary Spindle Cell Carcinoma Harboring RET fusion: A Case Report

Background: Pulmonary spindle cell carcinoma (PSCC), an exceptionally rare subtype of pulmonary sarcomatoid carcinoma (PSC), remains poorly characterized in terms of molecular alterations, rendering targeted therapy a promising option. RET gene fusions act as oncogenic drivers across multiple tumor types, and the emergence of selective RET tyrosine kinase inhibitors (TKIs) like pralsetinib has transformed the treatment of RET-fusion positive malignancies. However, their expanding clinical use underscores the need to better understand adverse event (AE) profiles, particularly severe toxicities. Case Description : This report describes a 60-year-old male who presented with progressive hemoptysis. Bronchoscopic biopsy, combined with pathological evaluation, immunohistochemical staining, and next-generation sequencing, confirmed the diagnosis of metastatic PSCC (cT4N2M1a, stage IVa) harboring a KIF5B-RET fusion. The patient was initiated on pralsetinib, achieving a sustained partial response for 21 months. Subsequently, he developed pralsetinib-induced grade 3 interstitial pneumonitis, which resolved following immediate drug discontinuation and systemic glucocorticoid intervention. A pralsetinib rechallenge at a reduced dose was attempted but resulted in recurrent pneumonitis, mandating permanent treatment cessation. The patient’s condition rapidly deteriorated, leading to his unfortunate demise. Conclusion : Pralsetinib is effective for RET-fusion positive PSCC, achieving long-term disease control. However, its risk of severe interstitial pneumonitis highlights the need for close monitoring. Clinicians should balance risks and benefits, especially for rechallenge, to optimize outcomes.