P-427: Smoldering multiple myeloma associated with a acquired von Willebrand syndrome , successfully treated by daratumumab, lenalidomide and dexamethasone

Introduction: Acquired von Willebrand syndrome (AvWS) is a rare entity with approximately 700 cases described in the literature, probably underestimated due to a wide range of clinical features. The syndrome results from a quantitative or qualitative defect, with symptoms identical to the constitutional form of von Willebrand disease. Many etiologies are responsible for this condition, mainly lymphoproliferative and myeloproliferative syndromes, as well as cardiac diseases. Several mechanisms have been involved depending on the etiology. Monoclonal gammopathy is the leading cause of AvWS, the mechanism encountered in this case is the production of anti-von Willebrand factor antibodies, which may be specific and inactivate von Willebrand factor (VWF) or aspecific, resulting in rapid clearance of VWF.

Methods: Here we report the case of a 84-year-old female, with no history of abnormal bleeding symptoms (spontaneous or provoked), regularly seen for recurrent digestive bleeds, requiring numerous blood transfusions (more than 25 transfusions in 4 years). A von Willebrand disease type 3 was confirmed with a von Willebrand factor antigen (vWF:Ag) at 3% (normal range, 50-120%), a activity of the cofactor of ristocetin (vWF:RCo) at 4% (normal range, 50-150%) and a coagulant activity of factor VIII (FVIII:C) at 4% (normal range, 50-150%). A complete work-up lead to the suspicion of an AvWS-SMM, with a monoclonal IgG kappa peak of 1.9g/L, and a bone marrow biopsy infiltrated by 15% plasma cells.

Results: Treatment consists in either controlling spontaneous bleeding or preventing surgically induced bleeding on the one hand and treating the underlying pathology on the other. However, in patients with asymptomatic lymphoproliferative malignancies, this decision can be difficult to make because of the impact of these therapies on the patient’s quality of life. First line options like DDAVP, IVIG treatment (in case of IgG peak) or VWF/FVIII concentrate should be proposed, but response are highly variable. Immunosuppressive agents such as rituximab, cyclophosphamide and azathioprine were ineffective in the majority of cases. When first line options are ineffective it is necessary to treat SMM. Treatment protocol is decided on a case-by-case basis, taking into account the benefit-risk ratio. Proteasome inhibitors and imide-based immunomodulatory drugs (IMiDs) can cause significant side effects, such as thrombocytopenia, and may require thromboprophylaxis that can complicate the management of such situations. Daratumumab is a human monoclonal antibody designed to specifically target the CD38 antigen expressed on plasma cells, approved for the treatment of multiple myeloma.

Conclusions: After unsuccessful trials with DDAVP, IVIG, rituximab and the need for a chronic use of Wilate®, a combination of daratumumab, lenalidomide and dexamethasone was started with a favorable outcome after two cycles of treatment, with normalization of all coagulation parameters and by the absence of recurrent digestive bleeding.