Successful Treatment of Refractory Immune Thrombotic Thrombocytopenic Purpura with Daratumumab

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare life-threatening disease manifested by thrombocytopenia, microangiopathic hemolytic anemia, and impaired functions of organs and systems due to the thrombosis of small arteries. The basis of the disease lies in the production of autoantibodies that eliminate or inhibit the activity of metalloproteinase ADAMTS13 (A Disintegrin and Metalloprotease with ThromboSpondin type 1 repeats, member 13). ADAMTS13 is one of the plasma proteins that cleave the high-molecular-weight von Willebrand factor. The standard iTTP treatment includes therapeutic plasma exchange, caplacizumab administration, and immunosuppressive therapy with glucocorticoids and rituximab. The present paper documents the first case report in Russia demonstrating the effective use of daratumumab in a 51-year-old female patient with refractory iTTP. The disease manifested with hemolytic anemia and deep thrombocytopenia with pronounced neurological disorders. The ADAMTS13 activity was 0 %, ADAMTS13 inhibitor titer was 3 units by Bethesda. As a result of the standard triplet therapy followed by addition of bortezomib, the thrombocyte count returned to normal, hemolysis ceased, and neurological symptoms regressed. At the same time, the hematological analysis showed zero activity of ADAMTS13 as well as persistent plasma protein inhibitor. The absence of this inhibitor and an increase of ADAMTS13 activity to 45 %, which correspond to complete iTTP remission, were achieved only after daratumumab administration. The paper comprehensively discusses the central features of the clinical case report and possible action mechanisms of various drugs used for the treatment of this life-threatening disease.