Fatal intracranial haemorrhage shortly after belzutifan initiation in von Hippel-Lindau (VHL) disease-associated haemangioblastoma.

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.