Daratumumab in Immune-mediated Thrombotic Thrombocytopenic Purpura

iTTP in an autoimmune disease caused by autoantibodies directed against the metalloproteinase ADAMTS13. Rituximab is the standard immune suppressive treatment suggested from international guidelines. However, 10-15% of patients do not achieve a sustained ADAMTS13 remission with rituximab, and a significant portion of responders eventually need re-treatment after 12 months or less. Other therapeutic options are scarce and based on old immunosuppressive agents or splenectomy, all burdened by relevant toxicity and lack of solid efficacy data. Recently, targeting CD20-negative long-lived plasma cells appears to be a promising strategy in refractory iTTP. The anti-CD38 monoclonal antibody daratumumab has been employed in selected iTTP patients with good results. However, evidence stems only from isolated case reports. The DarTTP study aims to collect evidence on a larger number of patients about the efficacy and safety of daratumumab in iTTP subjects who are refractory or intolerant to previous immunosuppressive treatments. The primary endpoint is the proportion of patients with ADAMTS13 activity levels above 20% of normal at 6 months from the first daratumumab administration.