Daratumumab in Ittp: A Case Series

Background: Immune-mediated thrombotic thrombocytopenia purpura is an idiopathic autoimmune hematological disorder which clinically presents with a transiently or persistently low platelet count, purpura, and hemorrhagic events. (Vaillant 2023, Rodeghiero 2009). It is caused by an idiopathic development of IgG autoantibodies against ADAMTS13 which causes a depletion of the protein (diagnostically <10% of normal activity) and a subsequent accumulation of von Willebrand factor (vWF) multimers leading to an increase in platelet adhesion, aggregation, and microthrombotic events (Bae 2022). The risk of mortality is largely associated with relapse, which occurs in anywhere from 30-50% of patients (Hovinga 2010, Selvakumar 2023). The current standard of care treatment for iTTP includes tissue plasma exchange (PLEX), capalacizumab (anti-vWF antibody) and immunosuppressive therapy (Zheng 2021). In relapsed patients, plasma exchange therapy is used, along with capalacizumab and either an increased dose of glucocorticoids or addition of another immunosuppressive therapy (cyclophosphamide, vincristine, cyclosporine, bortezomib, mycophenolate mofetil) (Farzana 2015). Recently, daratumumab, an anti-CD-38 monoclonal antibody approved for multiple myeloma and AL-amyloidosis, has demonstrated success in off-label use for treatment of relapsed and refractory iTTP (Vernava and Schmitt 2023). Aims: Two previous case reports have documented the use of daratumumab in the relapsed and refractory iTTP setting. In this case series, we reviewed the clinical and treatment course of two patients at our institution to assess overall treatment response and duration of response. Methods: We performed a literature search using the PubMed Google Scholar database from the time period of January 2010 to July 2024 with search criteria including “Daratumumab for iTTP” and “Daratumumab for relapsed or refractory TTP,” “Treatment for relapsed or refractory iTTP.” From our search results, two publications of case series and/or case reports were found involving iTTP relapsed or refractory disease and daratumumab used as next line of therapy (Van den Berg 2022; Aggarwal 2023). We assessed the clinical and treatment course of two patients at our institution as well as platelet response, duration of response, and patient demographics. Results: Both patients documented in this case series presented with multiply relapsed iTTP after rituximab failure. The two presented patients were both African American and above 40 years of age with obesity. This case series is the first to report treatment of iTTP with daratumumab in African American patients. Patient 1 has been on daratumumab maintenance therapy for a duration of two months upon the submission of this abstract and platelet count is stable at 142K and ADAMTS13 at 34.6%. Patient 2 had been on maintenance daratumumab and ADAMTS13 has remained stable for over a year with the most recent activity noted at 88.5% and platelet count of 172K. Summary/Conclusion: In conclusion, treatment with daratumumab led to normalization of ADAMTS13 and recovery of platelet counts in the two African American patients presenting with relapsed and refractory iTTP at our institution. As treatment with daratumumab becomes more favorable in this context, assessment of the demographic factors and clinical characteristics of patients and their response to the therapy will be important in determining which patient populations should receive daratumumab for treatment of their disease. We plan to conduct a meta-analysis of published literature of daratumumab in the relapse and refractory setting.