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| Home > Publications database > Daratumumab as a novel treatment option in refractory ITP. |
| Journal Article | DKFZ-2023-00161 |
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2023
Academic Press
Orlando, Fla.
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Please use a persistent id in citations: doi:10.1016/j.bcmd.2023.102724
Abstract: Primary immune thrombocytopenia (ITP) in adult patients typically presents as a repeatedly relapsing disease in need of multiple lines of therapy. Here we report the clinical courses of two patients, an 82-year-old female and a 54-year-old male, with primary ITP after multiple relapses and exhausted standard therapies, which we treated with the myeloma-licensed anti-CD38 monoclonal antibody daratumumab in an off-label setting. Daratumumab is known to target preferentially plasmablasts, short-lived plasma cells and long-lived plasma cells, with the latter being the major source of antiplatelet autoantibodies. Noteworthy, rituximab, a CD20 antibody, targets earlier steps in B-cell ontogenesis, thereby indirectly decreasing plasmablasts and short-lived plasma cells, but to a lesser extent long-lived plasma cells, which tend to persist after rituximab treatment. Several single-patient reports and case series have demonstrated successful treatment with daratumumab in ITP, autoimmune thrombocytopenia in Evans syndrome as well as other cytopenias or pure red cell aplasia after allogeneic stem cell transplantation or in congenital diseases, systemic lupus erythematodes and cold agglutinin disease. Our first patient with isolated primary ITP rapidly and lastingly responded to daratumumab plus tapered steroids, with platelet counts above 50 × 109/L within weeks and subsequently even stably within the normal range. Despite no objective response observed in the second patient, a lasting clinical stabilization was achieved. As the underlying mode of action, we hypothesize here daratumumab to effectively target long-lived plasma cells as the source of ITP-mediating autoantibodies, and suggest broader clinical evaluation of daratumumab in this potential indication.
Keyword(s): CD38 ; Daratumumab ; ITP ; Immune thrombocytopenia ; Long-lived plasma cells
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