Exceptional and Sustained Response to Belzutifan in Von Hippel-Lindau Disease-Associated Central Nervous System Hemangioblastoma

Abstract

Von Hippiel-Lindau (VHL) disease is a rare genetic disorder characterized by a variety of benign and malignant neoplastic growths arising in multiple different organ systems. About 60%-84% of patients develop hemangioblastomas, benign tumors comprised of newly formed blood vessels that often occur in the central nervous system (CNS) and retinas. Treatment options for this disease were limited before the Food and Drug Administration (FDA) approval of belzutifan, a HIF2α inhibitor. We present a case of a 25-year-old woman with VHL who underwent treatment with belzutifan over 18 months. It was noted that her CNS lesions decreased significantly in size over the course of her treatment, and she had minimal adverse effects. Her excellent and sustained therapeutic response to the treatment highlights the real-world clinical benefit of belzutifan and the possibility that this could play a crucial role in treating VHL by postponing or completely avoiding repeated surgical and radiotherapeutic intervention and their associated comorbidities.

Keywords: belzutifan; cerebellar hemangioblastoma; cns hemangioblastoma; hif-2 alpha inhibitor; hif2α; pheochromocytoma; renal cell carcinoma (rcc); targeted therapeutics; vhl-related syndrome; von hippel-lindau disease (vhl).

Figure 1. Initial magnetic resonance imaging (MRI) of the cervical spine (T1 post-contrast)

(A) Surveillance MRI showing multiple enhancing lesions throughout the neuraxis with the largest lesion at the cervicomedullary junction measuring 9 x 9 x 12 mm (yellow arrow). (B) Three-month follow-up MRI post the belzutifan treatment showing an interval decrease in size to 5 x 7 x 9 mm (yellow arrow).

Figure 2. Follow-up magnetic resonance imaging (MRI) of the cervical spine at 6, 9, and 12 months, demonstrating a sustained radiologic response (T1 post-contrast)

(A) Six-month cervical MRI. (B) Nine-month cervical MRI. (C) 12-month cervical MRI.

Figure 3. The 15- and 18-month follow-up magnetic resonance imaging (MRI) of the cervical spine (T1 post-contrast)

(A) The 15-month follow-up MRI of the cervical spine. (B) An 18-month follow-up MRI of the cervical spine evidenced a sustained radiologic response.

Figure 4. Comparison of patient's initial magnetic resonance imaging (MRI) of the cervical spine versus at 18-month follow-up (T1 post-contrast)

(A) Surveillance MRI showing multiple enhancing lesions throughout the neuraxis with the largest lesion at the cervicomedullary junction measuring 9 x 9 x 12 mm (yellow arrow). (B) An 18-month follow-up MRI post the belzutifan treatment showing a durable clinical response (yellow arrow).