Efficacy of CD38-Targeted Therapy in Severe, Multi-Agent Refractory Immune Thrombocytopenia: A Case Series

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by antibody-mediated platelet destruction, often driven by long-lived plasma cells (LLPCs) resistant to conventional therapies. While most patients respond to corticosteroids and intravenous immunoglobulin (IVIG), a subset develops life-threatening refractory disease. In this case series, we describe three patients aged 39, 85, and 58 with life-threatening, multi-agent refractory ITP and platelet nadirs < 2 × 10⁹/L who failed corticosteroids, IVIG, and thrombopoietin receptor agonists (TPO-RAs). Following salvage therapy with daratumumab, a monoclonal antibody targeting CD38, all three patients achieved rapid hematologic recovery, with platelet count normalization within 1 week. This accelerated response allowed for urgent clinical stabilization, including safe anticoagulation and surgical intervention. The efficacy of daratumumab likely stems from a dual mechanism: the depletion of CD38+ LLPCs and the immediate modulation of Fc-receptor-mediated platelet clearance. These observations suggest that CD38-targeted therapy can bypass traditional treatment resistance to achieve near-immediate remission in high-complexity, high-risk clinical settings. While these results are compelling, prospective clinical trials are warranted to define the long-term safety, durability, and optimal dosing of anti-CD38 therapies in refractory ITP populations.