Abstract Details

Title Belzutifan Beyond VHL; Case Series of Sporadic Hemangioblastomas and the Expanding Role of HIF-inhibitors

Topic Neuro-oncology

Presentation(s) P8 - Poster Session 8 (11:45 AM-12:45 PM)

Poster/Presentation
Number 6-009

Objective To retrospectively evaluate the clinical and radiographic response to off-label belzutifan therapy in patients with sporadic central nervous system (CNS) hemangioblastomas not associated with von Hippel-Lindau disease (VHL).

Background Approximately 25% of all CNS hemangioblastomas occur in the setting of autosomal dominant tumor suppressor syndrome von Hippel-Lindau disease. Belzutifan (Welireg, Merck) is an HIF2?? inhibitor that has been approved by the Food and Drug Administration (FDA) for treatment of VHL-associated hemangioblastomas. However, no FDA-approved systemic therapies currently exist for the majority of hemangioblastomas, which are sporadic and not associated with VHL disease. Tumorigenesis of both sporadic and VHL-associated hemangioblastomas is driven by dysregulation of the same hypoxia-inducible factor (HIF) pathway regulated by the VHL protein, but it remains unknown if belzutifan therapy would have a similar efficacy with off-label use in sporadic hemangioblastomas.

Design/Methods

We present three cases from a single tertiary care center, highlighting the off-label use of belzutifan in sporadic CNS hemangioblastoma with confirmation of negative germline testing for VHL.

Results Initiation of belzutifan led to radiographic improvement of hemangioblastoma and clinical improvement in the functional status of the patients in all three cases. This includes one case of isolated intramedullary thoracic spinal cord hemangioblastoma, one case with hemangioblastomas in the lumbar spine and cerebellum, and a third case with isolated hemangioblastoma of the cervicomedullary junction. Belzutifan was overall well-tolerated, with anemia noted in all three patients but without hypoxia or the indication for dose-reduction except in one patient who required a one-week break in belzutifan therapy after hemoglobin nadir of 9.7 g/dL; therapy was resumed after hemoglobin increased to >10 g/dL.

Conclusions These cases suggest that belzutifan may offer therapeutic benefit in sporadic CNS hemangioblastomas and support the need for prospective studies evaluating its safety and efficacy beyond VHL-associated disease.

Authors/Disclosures
Sanuri Gunawardena, MD (Sanuri Gunawardena) PRESENTER	Dr. Gunawardena has nothing to disclose.
Alyssa Lucas, MD	Dr. Lucas has nothing to disclose.
Andrew Dhawan, MD (Cleveland Clinic)	Dr. Dhawan has nothing to disclose.
Mina Lobbous, MD (Cleveland Clinic Foundation)	Dr. Lobbous has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Servier . Dr. Lobbous has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion Pharmaceuticals . Dr. Lobbous has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Telix pharmaceuticals . Dr. Lobbous has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Springworks Pharmaceuticals . Dr. Lobbous has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Springworks Pharmaceuticals . Dr. Lobbous has received publishing royalties from a publication relating to health care.

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