Optimizing treatment for Waldenström macroglobulinemia-associated acquired von Willebrand syndrome: a case report and literature review.

Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that is often caused by lymphoproliferative neoplasms such as Waldenström macroglobulinemia (WM). Treatment of AVWS comprises both the control of bleeding and the management of underlying diseases. As the frontline treatment of WM has rapidly evolved, the optimal regimen for AVWS secondary to WM (AVWS-WM) has yet to be elucidated. Hereby, we reported a 78-year-old male with AVWS-WM who was refractory to a rituximab-based regimen, experienced worsening bleeding when zanubrutinib was added and finally achieved a complete response to a bortezomib-based regimen. In the literature review, AVWS-WM was still rare, with only 39 cases reported. Both rituximab-based and bortezomib-based drugs are associated with a high response rate (18 out of 22 and 4 out of 5, respectively), while the Bruton tyrosine kinase inhibitor (BTKi) could result in worsening bleeding (3 out of 5) due to its inhibition of platelet function. In conclusion, both rituximab and bortezomib -based regimens are effective for AVWS-WM and regimens could be switched from one to another for refractory cases. Bruton tyrosine kinase inhibitor is not desirable front-line therapy for AVWS-WM as it could result in bleeding worsening due to its off-target inhibition of platelet function.