Daratumumab for immune thrombotic thrombocytopenic purpura

Abstract

Immune thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy. It is caused by a severe ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motifs, 13) deficiency due to circulating autoantibodies, and is associated with significant morbidity and mortality. Current treatment options include plasma exchange, immunosuppression, and caplacizumab. When remission is achieved, the risk of relapse is high, especially in patients with persistent ADAMTS13 deficiency. We report the eradication of persistent ADAMTS13 inhibitory autoantibodies and restoration of normal ADAMTS13 activity using the anti-CD38 antibody daratumumab in two patients with iTTP. One patient had a frequently relapsing course, and the other a treatment-refractory first episode. There were no relevant adverse drug reactions.

Figure 1.

Treatment of iTTP with the anti-CD38 antibody daratumumab. Clinical course and selected laboratory parameters from hospital admission to the most recent follow-up in 2 patients. Corticosteroids were started at a high dose and then tapered. In patient 2, daily administration of caplacizumab was reduced to every other day after 90 days. (A) Patient 1 with frequently relapsing iTTP; the course of his latest iTTP relapse is shown. (B) Patient 2 with a refractory first iTTP episode. Red line indicates titer of ADAMTS13 inhibitor (Bethesda units [BU] per mL; truncated at 2); blue line indicates ADAMTS13 activity (%); gray line indicates platelet count (× 10⁹/L).