A case study published in Therapeutic Advances in Hematology suggests that ibrutinib may have beneficial effects in patients with acquired von Willebrand syndrome (AVWS) that is secondary to Waldenström macroglobulinemia (WM). Monoclonal protein control may not, furthermore, be sufficient for predicting response to ibrutinib.

WM is characterized by IgM-secreting lymphoplasmacytic cell infiltration into bone marrow and other tissue. This is linked with AVWS, which occurs in up to 13% of patients with WM, and is associated with inhibited von Willebrand factor function, thereby increasing bleeding risk.

For these reasons, clinicians often recommend that patients with AVWS secondary to WM initiate treatment to reduce IgM levels, which may reverse the syndrome. There are, however, limited data on the efficacy of treatments, including chemotherapy, in this patient population. In this case study, researchers noted the efficacy of ibrutinib in a 63–year old female patient with AVWS secondary to WM.

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The patient had a history of Sjögren syndrome and presented with grade 1 bleeding symptoms, and had no reported familial history of bleeding. Both IgM (5.6 g/dL) and beta2 microglobulin (3.7 m/L) levels were elevated on initial testing. On analysis, both AVWS and WM were confirmed.

After an ineffective first-line treatment, the patient received ibrutinib monotherapy. A reduction in bleeding events was noted 2 weeks after therapy initiation, and a partial response was noted 2 months after therapy initiation, with IgM levels decreasing to 2.7 g/dL. At the time of this report, the patient had remained on ibrutinib for 26 months with only a 20-day discontinuation; bleeding events remained under control and the partial response was ongoing.

The researchers noted, however, that the response may be linked with reduced glycoprotein Ib receptor expression and von Willebrand factor increase in the patient’s peripheral blood.


Poza M, Íñiguez R, Zamanillo I, et al. Ibrutinib effect in acquired von Willebrand syndrome secondary to Waldenström macroglobulinemia. Ther Adv Hematol. 2021;12:20406207211039326. doi:10.1177/20406207211039326