Introduction: The systemic HIF-2 alpha inhibitor, belzutifan, has been approved for use in patients with VHL-associated renal cell carcinoma, central nervous system (CNS) hemangioblastomas, and pancreatic neuro-endocrine tumors. This drug has also shown promise in controlling VHL retinal hemangioblastomas (RH), but little work has been published on the use of the drug in this setting.
Methods: We conducted a retrospective review of patients with VHL-associated RH followed by the retina service at our institution who were treated with systemic belzutifan. Patient age, gender, genotype, presence of systemic tumors, indication for the drug, initial dose, adjusted dose, side effects, and tumor response were recorded. We also conducted a literature search for all manuscripts describing the effect of belzutifan on VHL-associated ocular tumors.
Results: We identified 12 eyes of 7 patients with VHL-associated ocular tumors who were treated with belzutifan at our institution. Of these, 5 eyes of 3 patients had progressing ocular tumors when belzutifan was started. Of the 7 total patients, 2 were treated for renal cell carcinoma, 2 for CNS hemangioblastomas, 2 for RH, and one for pancreatic neuro-endocrine tumor. Initial dose was 120 mg PO daily in 6 patients and 80 mg PO daily in one patient. The dose was reduced in all but one patient due to side effects. The ocular tumors were controlled in all patients with average follow up of 13 months (range 4-24 months). Literature review identified 7 manuscripts that described belzutifan-mediated control of ocular tumors in patients with VHL-associated RH in 21 patients.
Conclusion: The drug belzutifan shows great promise for controlling RH and preventing vision loss in patients with VHL. Further work needs to address the optimal dose, role of the drug as a neo-adjuvant therapy, and long-term efficacy and tolerability of the drug in a larger cohort of patients with ocular tumors.
