Daratumumab for relapsed refractory immune thrombotic thrombocytopenic purpura: initial response and long-term follow-up

Background: Management of patients with refractory or frequently relapsing (r/r) immune thrombotic thrombocytopenic purpura (iTTP) remains challenging, with no established consensus on optimal therapeutic strategies. In recent years, plasma-cell depletion with daratumumab, a monoclonal antibody against CD38, has been used successfully for treatment-resistant patients with various autoimmune diseases, including iTTP, although long-term data remain limited. Objectives: To assess the efficacy, durability, and safety of daratumumab in patients with r/r iTTP. Methods: We retrospectively analyzed 8 daratumumab treatment episodes in 5 patients with r/r iTTP, treated at 3 Swiss tertiary centers, with a median follow-up after daratumumab of 44 months (range, 34-65 months). Serial a disintegrin and metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS-13) activity and inhibitor levels, clinical outcomes, and adverse events were assessed. Results: Daratumumab induced rapid and robust ADAMTS-13 recovery in 7 of 8 episodes. All responding patients achieved complete ADAMTS-13 remission within 1 and 3 weeks. Mean ADAMTS-13 relapse-free survival following daratumumab was 32 months, with 7 of 8 episodes remained in complete ADAMTS-13 remission at 12 months. Nonetheless, ADAMTS-13 relapse occurred in 4 of 5 patients during long-term follow-up. Two patients experienced mild to moderate infusion-related adverse reactions. Conclusion: Our findings support daratumumab as an effective and well-tolerated therapeutic option for patients with r/r iTTP, particularly those unresponsive to rituximab and other immunosuppressants.