The Outcome of Central Nervous System Hemangioblastomas in Von Hippel-Lindau (VHL) Disease Treated with Belzutifan: A Single-Institution Retrospective Experience

Abstract

Abstract Purpose: Belzutifan is a Hypoxia Inducible Factor 2-alpha inhibitor approved in 2021 by the FDA for the treatment of renal cell carcinoma (RCC) in patients with Von-Hippel Landau (VHL) disease. These patients can also present with central nervous system (CNS) hemangioblastomas (HBs). We aim to study the effectiveness and adverse effects of belzutifan for CNS HBs, by reporting our preliminary institutional experience. Methods: We present a series of VHL patients with CNS HBs undergoing treatment with belzutifan for RCC. All the included patients met the RECIST inclusion criteria. The clinical and radiological outcome measures included: Objective response rate (ORR), time-to-response (TTR), adverse events (AE), and patient response. Patient response was classified as partial response (PR), complete response (CR), progressive disease (PD), or stable disease (SD). Results: Seven patients with 25 HBs were included in our study. A Belzutifan dose of 120 mg/day PO was administered for a median of 13 months (range 10–17). Median follow up time was 15 months (range 10–24). An ORR of 71% was observed. The median TTR was 5 months (range: 1–10). None of the patients showed CR, while 5 patients (71.4%) showed PR and 2 (28.5%) showed SD. Among patients with SD the maximum tumor response was 20% [increase/decrease] of the lesion diameter. All the patients experienced decreased hemoglobin concentration, fatigue, and dizziness. None of the patients experienced severe anemia (grade 3–4 CTCAE). Conclusion: Belzutifan appears to be an effective and safe treatment for CNS hemangioblastoma in VHL patients. Further clinical trials to assess the long-term effectiveness of the medication are required