Fatal intracranial haemorrhage shortly after belzutifan initiation in von Hippel-Lindau (VHL) disease-associated haemangioblastoma.
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ICR Authors
Authors
Shepherd, STC
Kelly-Morland, C
Drage, S
Brady, AF
Macwana, R
Pickering, L
Larkin, J
Hill, P
Turajlic, S
Kelly-Morland, C
Drage, S
Brady, AF
Macwana, R
Pickering, L
Larkin, J
Hill, P
Turajlic, S
Document Type
Journal Article
Date
2025-05-01
Date Accepted
2025-04-15
Abstract
BACKGROUND: Belzutifan, a selective hypoxia-inducible factor-2α inhibitor, is approved for von Hippel-Lindau (VHL) disease-associated tumours and is Food and Drug Administration-approved for the management of advanced sporadic clear-cell renal-cell carcinoma. While belzutifan has demonstrated efficacy across VHL-related lesions, real-world safety data remain limited. PATIENTS AND METHODS: We report a fatal intracranial haemorrhage occurring within 72 h of belzutifan initiation in a patient with VHL-associated central nervous system haemangioblastomas (CNS-HBs). RESULTS: This represents the third post-marketing case of early haemorrhage involving CNS or spinal haemangioblastomas, following previously reported spinal and cerebellar bleeds. Although CNS-HBs are highly vascular, spontaneous haemorrhage is exceedingly rare. The clustering of haemorrhagic events in these cases, within days of treatment initiation, suggests a rare but potentially serious adverse event not currently listed on regulatory labels. CONCLUSIONS: This case highlights the importance of pharmacovigilance as belzutifan use expands into broader real-world populations, particularly in rare disease settings where trial cohorts are small and long-term safety data are limited.
Citation
ESMO Open, 2025, 10 (5), pp. 105109 -
Source Title
ESMO Open
Publisher
ELSEVIER
ISSN
2059-7029
eISSN
2059-7029
Collections
Research Team
Directorate Clin Studies