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Belzutifan in adults with VHL-associated central nervous system hemangioblastoma: a single-center experience

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Abstract

Purpose

Belzutifan is a selective inhibitor of hypoxia-inducible factor 2 alpha (HIF-2a) that has emerged as a targeted therapy option for Von Hippel–Lindau (VHL) syndrome-associated tumors with recent FDA approval. There is limited real-world evidence regarding safety and efficacy in CNS hemangioblastoma. Our objective was to report on our clinical experience with belzutifan in adult patients with VHL-associated CNS hemangioblastoma.

Methods

We retrospectively reviewed our institutional experience of belzutifan in adult patients (> 18 years of age at time of therapy) with VHL and craniospinal CNS hemangioblastomas not amenable to surgical resection. The period for study review was October 2021 to March 2023.

Results

4 patients (all female) with a median age of 36 years at time of belzutifan initiation were included. Median duration of therapy at last follow-up was 11 months (6–17 months). All patients had radiographic response to therapy after a median of 3 months (2–5 months), with maximal response to therapy after a median of 8 months (3–17 months). Therapy was well tolerated, with the most common adverse effect being anemia. No patients had treatment pauses or dose adjustments due to belzutifan-related toxicity. No patients experienced hypoxia.

Conclusion

We showed that belzutifan is safe and well-tolerated with strong disease response for CNS hemangioblastoma in adults with VHL, supporting continued use of belzutifan in this patient population. Future studies should assess duration of treatment, effects of cessation after long-term use, and markers of therapeutic response.

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Acknowledgements

The authors would like to thank all included patients.

Funding

There was no targeted funding for this report.

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Authors and Affiliations

  1. Department of Neurology, Mayo Clinic, Rochester, MN, 55905, USA

    Bryan J. Neth, Jessica White, Joon H. Uhm & Ugur Sener

  2. Department of Medical Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Mason J. Webb, Joon H. Uhm & Ugur Sener

  3. Department of Clinical Genomics, Mayo Clinic, Rochester, MN, 55905, USA

    Pavel N. Pichurin

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  1. Bryan J. Neth
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Contributions

BN: design and conception, data collection, interpretation of results, writing the first draft; MW, JW: data collection, interpretation of results, critical review and editing of manuscript for intellectual content; JU, PP: interpretation of results, critical review and editing of manuscript for intellectual content; US: design and conception, interpretation of results, critical review and editing of manuscript for intellectual content.

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Correspondence to Ugur Sener.

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Neth, B.J., Webb, M.J., White, J. et al. Belzutifan in adults with VHL-associated central nervous system hemangioblastoma: a single-center experience. J Neurooncol 164, 239–247 (2023). https://doi.org/10.1007/s11060-023-04395-3

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  • DOI: https://doi.org/10.1007/s11060-023-04395-3

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