Real-World Effectiveness and Pharmacogenetics of Belzutifan in VHL Syndrome: The BELIEVE-VHL Trial

Inclusion Criteria: * Age ≥ 14 years. * Clinical or genetic confirmation of von Hippel-Lindau (VHL) syndrome. * Presence of measurable or progressive VHL-associated tumors, as defined by RECIST 1.1 or disease-specific imaging criteria. * ECOG performance status of 0-2. * Adequate bone marrow, hepatic, and renal function as defined by laboratory reference values. * Ability to swallow oral medication. * Provision of written informed consent prior to enrollment. Exclusion Criteria: * Age \< 14 years. * Absence of a confirmed diagnosis of von Hippel-Lindau (VHL) syndrome. * Presence of an active malignancy outside the VHL tumor spectrum within the past 3 years, except for adequately treated basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, or other malignancies considered cured for \>2 years. * Known hypersensitivity or allergic reaction to belzutifan or any excipient in the formulation. * History of severe or uncontrolled cardiovascular disease, including but not limited to unstable angina, myocardial infarction within the past 6 months, congestive heart failure requiring treatment, or uncontrolled hypertension. * Active infectious diseases, including HIV, hepatitis B, or hepatitis C. * Immunosuppressed status, whether due to underlying disease or ongoing therapy. * History of significant bleeding disorders, including bleeding diathesis, thrombocytopenia, or coagulopathy. * Radiotherapy administered within 4 weeks prior to study enrollment. * Major surgical procedure, including for VHL-related tumors, within 4 weeks prior to study enrollment, or immediate need for surgical intervention for tumor management. * Malabsorption secondary to prior gastrointestinal surgery or active gastrointestinal disease. * Current use of concomitant medications known to interact with belzutifan and significantly alter its bioavailability. * Anticipated low adherence to or planned interruption of belzutifan therapy.