Successful use of lenalidomide to treat refractory acquired von Willebrand disease associated with monoclonal gammopathy

Abstract

Acquired von Willebrand syndrome (AVWS) is a rare hematologic disorder characterized by quantitative or qualitative defects of von Willebrand factor (vWF), a protein crucial for normal hemostasis. AVWS has been described in association with several pathologic entities with varied mechanisms. Among these, lymphoproliferative disorders are the most common, with monoclonal gammopathy of undetermined significance (MGUS) being the most frequently reported. AVWS in this setting is commonly associated with the development of bleeding that is clinically challenging to manage due to accelerated clearance of vWF, limiting the utility of many conventional treatment modalities such as DDAVP or vWF/FVIII. We report a case of a 43-year-old male who was sent to our institution for new-onset easy bruising and laboratories concerning for von Willebrand disease (vWD). Further diagnostic workup revealed evidence of an IgG monoclonal gammopathy and findings suggestive of vWF inhibition. Ultimately, he was found to have monoclonal gammopathy of clinical significance (MGCS)-associated AVWS refractory to conventional treatment but responsive to lenalidomide and dexamethasone. This case suggests that lenalidomide may be suitable for patients with AVWS secondary to MGCS.

Acquired von Willebrand syndrome in a patient with monoclonal gammopathy of unknown significance: A case report

“…Interestingly, in another report of a patient with IgG kappa MGUS-associated AvWS, bortezomib was ineffective at a dose of 1.3 mg/m 2 given biweekly in cycles of 2 weeks on and 1 week off and was instead successfully treated with lenalidomide. 13 There is also evidence that suggests lenalidomide has anti-angiogenic activity and was effective in controlling intractable GI bleeding in a patient who had persistent bleeding despite eradication of the paraprotein with rituximab. 16 Our case demonstrates that clonal-directed therapy with three cycles of bortezomib resulted in eradication of the paraprotein and a durable remission of MGUS-associated AvWS.…”

“…[10][11][12] There are scarce data on use of other plasma cell-depleting agents, such as lenalidomide and bortezomib, in refractory cases. 3,[12][13][14][15][16] Herein, we report a case of MGUS-associated AvWS successfully treated with bortezomib after short-term response to factor replacement in combination with IVIG and intolerance to rituximab. To our knowledge, there have only been two other cases described in the literature where bortezomib resulted in long-term remission of MGUS-associated AvWS, both in patients with IgG kappa MGUS.…”

“…This could explain why rituximab has been found to be ineffective, as it does not target the plasma cell clone 10–12 . There are scarce data on use of other plasma cell‐depleting agents, such as lenalidomide and bortezomib, in refractory cases 3,12–16 . Herein, we report a case of MGUS‐associated AvWS successfully treated with bortezomib after short‐term response to factor replacement in combination with IVIG and intolerance to rituximab.…”

Acquired Von Willebrand Syndrome in a patient with Monoclonal Gammopathy of Unknown Significance: a case report

“…Interestingly, in another report of a patient with IgG kappa MGUS-associated AvWS, bortezomib was ineffective at a dose of 1.3 mg/m 2 given biweekly in cycles of 2 weeks on and 1 week off and was instead successfully treated with lenalidomide (13). There is also evidence that suggests lenalidomide has anti-angiogenic activity and was effective in controlling intractable GI bleeding in a patient who had persistent bleeding despite eradication of the paraprotein with rituximab (16).…”

“…This could explain why rituximab has been found to be ineffective, as it does not target the plasma cell clone (10)(11)(12). There is scarce data on use of other plasma cell depleting agents such as lenalidomide and bortezomib in refractory cases (3,(12)(13)(14)(15)(16). Herein, we report a case of MGUS associated AvWS successfully treated with bortezomib after short-term response to factor replacement in combination with IVIG and intolerance to rituximab.…”