Zanubrutinib‑Induced Symmetrical Soft Tissue Forearm Swelling in a Patient With Waldenström Macroglobulinemia

Zanubrutinib is a second-generation Bruton tyrosine kinase (BTK) inhibitor approved for the treatment of several indolent B-cell lymphomas. Although it has a more favorable safety profile than its predecessor, ibrutinib, rare adverse effects continue to emerge with broader clinical use. We report the case of an 87-year-old man with Waldenström macroglobulinemia (WM) who developed bilateral, non-pitting, soft tissue swelling of the forearms approximately 16 weeks after initiating zanubrutinib 160 mg orally twice daily. The swelling extended from the elbows to the hands, was symmetrical, non-tender, and not associated with any other symptoms. Doppler ultrasound ruled out deep vein thrombosis, and no alternative causes such as trauma, infection, or hypoalbuminemia were identified. A 50% dose reduction of zanubrutinib led to partial improvement, while complete resolution was observed 12 weeks after drug discontinuation. Unlike previously reported cases of BTK inhibitor-associated edema, which typically involve the lower extremities and present unilaterally or with associated skin changes, this case is unique in its bilateral presentation and upper extremity location without cutaneous involvement. The mechanism remains unclear but may involve vascular endothelial dysfunction or altered lymphatic drainage. Prompt recognition of this atypical presentation is essential for avoiding unnecessary interventions and optimizing therapeutic decisions.