Daratumumab for Refractory and Frequently Relapsing Immune Thrombotic Thrombocytopenic Purpura – a Case Series with Long-Term Follow-up

Introduction: Immune thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy (TMA) caused by inhibitory autoantibodies to ADAMTS13 [1]. Management of acute iTTP consists of daily therapeutic plasma exchange (TPE), administration of the anti-VWF nanobody caplacizumab, and immunosuppression with corticosteroids [2] [3] [4]. Relapse occurs in at least 30% of patients and some are refractory to treatment or show a frequently relapsing course (r/r iTTP) [5] [6]. Management of these patients is challenging and no clear treatment recommendations exist. Daratumumab, an anti-CD38 antibody, has emerged as an efficacious and safe therapeutic option for a variety of autoimmune diseases, including iTTP [7]. We present a series of patients with r/r iTTP which we have treated with daratumumab, with a median follow-up of 43 months.

Method: Our retrospective analysis included 8 treatment episodes with daratumumab in 5 patients from 3 Swiss centres. Patient-level data from January 1^st, 2014 through July 1^st, 2024 included disease course, treatment with response and adverse reactions, ADAMTS13 activity and inhibitor. ADAMTS13 recovery following treatment was defined as partial (ADAMTS13 activity>20%) and complete (>50%).

Results: We evaluated 8 treatment episodes with daratumumab in 5 r/r iTTP patients. Prior to daratumumab, a median of 2 (range, 2-6) other immunosuppressive therapies were given. A median number of 6 (range, 4-8) daratumumab doses was administered per patient, either as an intravenous infusion (16 mg/kg bw) or subcutaneous injection (1800 mg). One patient received continuing monthly daratumumab injections of 1800 mg subcutaneous following his initial six weekly injections. In all cases, daratumumab was initiated to reverse ADAMTS13 deficiency while the patients were still in clinical remission. Infusion-related adverse events were observed in 2 patients with grades 1 and 2, respectively. No other adverse events related to daratumumab were observed. ADAMTS13 response was observed in 87.5% (7/8 treatment episodes), including 7 complete ADAMTS13 responses. The mean ADAMTS13 activity at response was 70% (n=7, SD 23.1%). The median time to response was 2.5 weeks (range, 2-4). The median duration of this response was 19 months (max. 37 months, 1 patient was no longer responsive during his last treatment episode). After a median follow-up of 43 months, 85.7% of those patients who had been responsive (6/7 cases) maintained this response at 12 months and 28.5% of patients (2/7) at 24 months. Ultimately, relapse following daratumumab therapy was seen in 85% of patients (6/7 cases).

Conclusion: Our retrospective evaluation indicates that daratumumab could be an efficacious and safe option for r/r iTTP patients failing to respond to rituximab. Prospective studies are warranted to confirm the long-term efficacy and safety of daratumumab treatment in such patients.

Publikationsverlauf

Artikel online veröffentlicht:
13. Februar 2025

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