BMJ Case Rep. 2026 Sep 29;19(9):e272742. doi: 10.1136/bcr-2026-272742.
ABSTRACT
We report the first known case of uveitis and keratitis caused by zanubrutinib, a second-generation Bruton tyrosine kinase (BTK) inhibitor in a patient with Waldenström macroglobulinaemia (WM). The patient was a man in his early 50s who had WM, a type of non-Hodgkin's lymphoma which produces monoclonal IgM. He developed posterior uveitis, characterised by vitreous and retinal infiltrates, while taking 280 mg of oral ibrutinib, the targeted therapy for WM. This is a known, rare adverse event of first-generation BTK inhibitors such as ibrutinib. The inflammation resolved spontaneously after discontinuing ibrutinib, without steroid intervention. Causality was confirmed when the uveitis and infiltrates promptly recurred on re-challenge with oral ibrutinib at a half-dose of 140 mg. A subsequent switch to the oral second-generation BTK inhibitor zanubrutinib resulted in an immediate, severe panuveitis with keratitis, which resolved on discontinuation of the drug. This definitive challenge-de-challenge-re-challenge sequence provides compelling evidence for a potential class effect of BTK inhibitors and ocular inflammation. Clinicians should be vigilant in monitoring for ocular symptoms in those taking zanubrutinib, especially if they have experienced sensitivity to other BTK inhibitors.
PMID:42810753 | DOI:10.1136/bcr-2026-272742