In patients with acquired hemophilia A (AHA), clearance of factor VIII (FVIII) inhibitors is needed with treatment, particularly in those with refractory disease, according to findings from 4 case reports published in the Journal of Thrombosis and Haemostasis.
Individuals with AHA are prone to experiencing episodes of bleeding, which are associated with a decrease in FVIII activity caused by FVIII antibodies. AHA is a rare disorder caused primarily by immunoglobulin (Ig) G4 autoantibodies and, to a lesser extent, by IgA or IgM autoantibodies. These antibodies can be linked to severe bleeding symptoms. Upon diagnosis of AHA, immunosuppressive therapy must be initiated immediately.
With the effects of many of the commonly used immunosuppressants and immunomodulators in patients with AHA remaining to be elucidated, the urgency exists to develop new agents that are able to effectively clear antibodies.
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Daratumumab is an IgGκ monoclonal antibody that binds to the glycoprotein CD38, which is known to be highly expressed on the surface of plasma cells. The agent is frequently used to clear plasma cells and antibodies in patients with multiple myeloma; however, few reports on daratumumab therapy in individuals with AHA are available.
Read more about experimental therapies for hemophilia
Because daratumumab can deplete CD38-positive plasma cells, the researchers theorized that production of FVIII inhibitors can be decreased by depletion of FVIII antibody-secreting plasma cells among individuals with AHA. The current study describes the case reports of 4 patients with AHA who were refractory to first- and second-line therapies.
Patient 1 was a 37-year-old female with AHA that was diagnosed because of hematuria reported at 24 weeks’ gestation. Her FVIII activity (FVIII: C) was 0.7 IU/dL and her FVIII inhibitor titer was 62.8 Bethesda units (BU). Following administration of daratumumab combined with methylprednisolone at 1 year after delivery, complete remission was attained after 20 weeks of treatment.
Patient 2 was a 32-year-old male who was diagnosed with AHA with an FVIII: C of 0.7 IU/dL and an FVIII inhibitor titer of 65.9 BU. He achieved complete remission after 29 weeks of daratumumab treatment.
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Patient 3 was a 73-year-old male who was diagnosed with AHA because of skin ecchymosis. His FVIII: C was 0.4 IU/dL and his FVIII inhibitor titer was 1620 BU. Daratumumab combined with dexamethasone was administered once weekly. After 2 weeks, his FVIII inhibitor titer decreased significantly and was below 20 BUs after 4 weeks of therapy. He stopped daratumumab 16 weeks ago, and although he declined inhibitor testing, it is assumed that he has attained complete remission.
Patient 4 was a 70-year-old male who was diagnosed with AHA because of skin ecchymosis. His FVIII: C was 0.8 IU/dL and his FVIII inhibitor titer was 13.6 BU. After failing a number of treatments, daratumumab combined with glucocorticoids once weekly was initiated. Following 14 daratumumab treatments, his FVIII: C reached more than 200% and his FVIII inhibitor was 0 BU. He is currently considered to be in complete remission.
“[D]aratumumab combined with glucocorticoids could be an option for [patients with] refractory
AHA . . . without increasing opportunistic infections,” the authors noted. “We need more clinical trials to confirm the efficacy and to determine whether it can be used in the first-line treatment of AHA in the future,” they concluded.
Reference
Liu W, Liu J, Xue F, Yang R, Zhang L. Anti-CD38 antibody for refractory acquired hemophilia A. J Thromb Haemost. Published online March 18, 2023. doi:10.1016/j.jtha.2023.03.010
