Daratumumab in immune-mediated thrombotic thrombocytopenic purpura: emerging evidence for plasma cell–targeted therapy

INTRODUCTION: Immune mediated thrombotic thrombocytopenic purpura is a life threatening autoimmune thrombotic microangiopathy caused by severe ADAMTS13 deficiency due to inhibitory autoantibodies. Despite plasma exchange, corticosteroids, rituximab, and caplacizumab, some patients develop refractory disease or persistent and relapsing ADAMTS13 deficiency. OBJECTIVES: To summarize the mechanistic rationale, clinical efficacy, safety, and potential therapeutic role of daratumumab in refractory or frequently relapsing immune mediated thrombotic thrombocytopenic purpura. METHODS: A structured narrative review was conducted across five major bibliographic databases, PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and Web of Science, from database inception through September 13, 2026. Searches of major hematology journal databases were also performed. Case reports, case series, registry analyses, multicenter cohort studies, and conference abstracts describing the use of daratumumab in acquired immune-mediated thrombotic thrombocytopenic purpura (iTTP) were included. Clinical setting, treatment regimen, ADAMTS13 response, time to response, relapse, and adverse events were extracted and qualitatively synthesized. Because reports differ in populations, endpoints, concomitant therapy, and possible patient overlap, findings were synthesized qualitatively without a pooled response estimate. RESULTS: Six key clinical reports involving more than 40 patients were identified. Most patients had received multiple previous therapies, including plasma exchange, corticosteroids, rituximab, and caplacizumab. Daratumumab was administered intravenously at 16 mg/kg or subcutaneously at 1,800 mg, usually weekly for two to six doses. Across the available reports, ADAMTS13 recovery was observed in a substantial proportion of treated patients, although reported response rates varied according to the populations studied and the thresholds used to define response. Recovery commonly occurred within several weeks. Multicenter reports also described sustained remission in a proportion of responders, although biochemical relapse remained frequent during follow-up. Adverse events were generally manageable, with predominantly mild infusion reactions and infrequent serious infections. Other individualized treatment strategies described after rituximab failure or intolerance include bortezomib, optimized or alternative anti-CD20 therapy, ciclosporin, azathioprine, and mycophenolate. CONCLUSION: Daratumumab is a promising plasma cell directed therapy for rituximab refractory or frequently relapsing immune mediated thrombotic thrombocytopenic purpura. Prospective studies are required to define its role within treatment algorithms.