Tumor Lysis Syndrome Induced by Selpercatinib in Rearranged During Transfection (RET) Fusion-Positive Non-Small-Cell Lung Cancer

Tumor lysis syndrome (TLS) is a rare but potentially fatal oncologic emergency in patients with solid tumors. Though well documented in hematologic malignancies, TLS in non-small-cell lung cancer (NSCLC) has been infrequently reported. We report the case of a 78-year-old woman diagnosed with stage IVB NSCLC harboring a KIF5B-rearranged during transfection (RET) fusion. Selpercatinib was initiated at 160 mg twice daily. At baseline, the patient had normal renal function and no classical laboratory risk factors for TLS. By day seven of treatment, biochemical abnormalities fulfilled the Cairo-Bishop criteria for laboratory and clinical TLS: uric acid rose to 13.3 mg/dL, phosphate to 5.4 mg/dL, and creatinine to 2.15 mg/dL. Selpercatinib was discontinued, and treatment with intravenous hydration, febuxostat, and furosemide was initiated. No arrhythmias or seizures occurred. Biochemical abnormalities resolved within five days. Selpercatinib was successfully resumed without recurrence of TLS. A partial radiographic response was observed during the following four months. To our knowledge, this is the first reported case of TLS induced by selpercatinib in RET fusion-positive NSCLC. This case highlights that potent targeted therapy can trigger TLS even in the absence of conventional risk factors. Early recognition and aggressive management are essential to mitigate risk and allow continuation of effective treatment.