Abstract Introduction Relapsed or refractory immune thrombocytopenic purpura (ITP) remains a therapeutic challenge in hematology and represent a serious impairment to our patients' quality of life. These patients are often exposed to frequent steroid treatments with corresponding side effects and are at risk of serious bleeding complication. First-line therapy includes steroids and intravenous immunoglobulins which in most cases leads to a rapid increase in platelet count. Still, about two-thirds of ITP cases in adults develop into chronic ITP and other treatment options like TPO-agonists, SYK-inhibitors, immunosuppressive treatments, rituximab or in severe cases even splenectomies are needed. Since, one of the major pathomechanisms in ITP is the production of autoantibodies against thrombocytes by plasma cells, we started to follow a novel causative therapeutic approach with daratumumab at our center for this difficult to treat patient collective. Daratumumab is one of the most important substances in modern myeloma therapy and can very effectively deplete antibody-producing plasma cells by targeting CD38. As we were one of the first centers to use daratumumab for ITP, we would like to share long time experiences with this strategy. Results Since 2020 we treated eight ITP patients (female: 4, male: 4; median age: 61 years (range 22-87 years)) with daratumumab (1800 mg doses, induction cycle with 4 weekly applications, further therapy regimens were individual, median number of applications: 9.5, range 4-17). Three patients (37.5 %) had secondary ITP. All patients were previously treated with TPO agonists and rituximab and had at least four prior ITP therapy lines with a median disease duration of six years (range: 1-35 years). Five patients (62.5 %) responded to the therapy (defined as Tc count 50 Gpt/L, median time to response: 2 weeks, range 1-10). Two of these patients had a rapid relapse after two and four months. In one of these cases a daratumumab re-exposure (in combination with Romiplostim) 10 months after relapse led to another sustained remission (9 months at last follow-up). The other three responders have an impressive long-term response with ongoing complete remission in the last follow-ups after 24, 32, and 51 months without any major bleedings or need for further ITP therapy. In addition, despite many earlier immunomodulatory therapies and frequent use of corticosteroids, we did not observe serious infectious complications due to daratumumab treatment. Conclusions For five years now, we have been treating ITP patients with Daratumumab when standard therapy options were failing with an impressing response rate of 62,5% and a stable long-term outcome up to 51 months. It should be noted that the time until response can take up to 10 weeks and therefore therapy should not be discontinued too early if an adequate increase in platelet count has not yet been reached. Another important observation is that in one relapsed case after initial response to daratumumab, we were able to achieve a second remission with a combination therapy of daratumumab and romiplostim, which indicates that daratumumab re-exposure is a considerable option. In recent years, another CD38 antibody (CM313, Lumrotatug) has been developed for ITP, which also showed an excellent response with an overall response rate of 95% in a phase 2 study for patients with refractory/chronic ITP (Chen et al., NEJM, 2024). This further supports our therapeutic concept of plasma cell depletion in ITP. Another exciting immunological approach is the use of CD19-directed CAR-T cells for B cell depletion in ITP, which also shows promising first results (Trautmann-Grill et al, Lancet, 2025). However, it should be considered that CAR-T cell therapy is a much more invasive procedure for the patient and involves considerable costs compared to antibody-based therapies. Overall, we consider daratumumab as a safe and promising therapy option in refractory/chronic ITP patients. Looking ahead, we are also exploring the possibility of combining daratumumab with other substances to achieve broader and deeper depletion of the B cell compartment, which could potentially further improve efficacy and long-term outcomes. However, further randomized studies are needed to determine the exact role of Daratumumab in ITP.
Ralph Wäsch (Mon,) studied this question.