INNV-37. BELZUTIFAN IMPACT ON VHL-ASSOCIATED CNS HEMANGIOBLASTOMAS

Abstract

Abstract INTRODUCTION CNS hemangioblastomas are a leading cause of morbidity and mortality among patients with Von Hippel-Lindau (VHL) disease. Belzutifan, a selective hypoxia-inducible factor (HIF-2a) inhibitor, has been approved for the treatment of hemangioblastomas in VHL patients; however, long-term efficacy and safety data are lacking. METHODS The authors performed a retrospective chart review of all type Ia VHL with symptomatic CNS hemangioblastomas who were treated with Belzultifan at the Moffitt Cancer Center from August 2021 to June 2023. Patient demographics, clinical characteristics, tumor characteristics, and complications were assessed. Patients were re-evaluated with repeat CNS imaging every 3-6 months. RESULTS Eleven patients were identified. Median age is 35 years (IQR: 24-56) and 4/11 patients (36%) are female. Eight out of 11 patients had accessible genetic testing and 87.5% had a missense mutation in the VHL gene. Two patients (18%) had pathology-proven RCC and no patients had pheochromocytomas. One patient (9%) had complete response, eight (73%) had partial response, and two patients (18%) had stable disease at 6 months. Treatment was stopped on 8 patients once they reached stable response to treatment, with 1 patient at 6 months (12.5%), 5 patients at 1 year (62.5%), and 2 patients at 16 months (25%). Five out of 8 patients (62.5%) had sustained response (≥ 3 months) during the time Belzutifan was held. Treatment was restarted on the 3 patients who had progression of disease and all 3 had positive response to treatment at 3 months. All patients had anemia (CTCAE grade 1-2), but did not require blood transfusions, and 1 patient had visual disturbances after restarting Belzutifan. CONCLUSION All patients responded positively to Belzutifan based on surveillance CNS imaging, with no major side effects. The majority of patients had sustained response after having stopped the drug for 3 months.