Abstract Number: PB1002
Meeting: ISTH 2022 Congress
Background: Acquired hemophilia A (AHA) patients with poor prognostic markers, factor VIII (FVIII) coagulant activity (FVIII:C) < 1 IU/dL or FVIII inhibitor titer >20 Bethesda units (BU)/mL, may fail to achieve remission after combined immunosuppressive therapy (IST). Anti-CD38 monoclonal antibody daratumumab has a potential for inhibitor eradication by depleting anti-FVIII autoantibody-producing plasma cells in those patients.
Aims: We describe a case of AHA with major bleeding secondary to high-titer FVIII inhibitors treated by daratumumab.
Methods: A 33-year-old previously healthy Thai man spontaneously developed large intramuscular hematomas at the right thigh and left buttock. Undetectable FVIII:C and high-titer FVIII inhibitors by Nijmegen-Bethesda assays confirmed AHA diagnosis. While bypassing agents (BAs), recombinant activated factor VII and activated prothrombin complex concentrate, were administered for hemostatic treatment, prednisolone 1 mg/kg/day plus 4-week oral cyclophosphamide 1.5 mg/kg/day were prescribed. Four weekly doses of intravenous daratumumab 16 mg/kg were added after an uncontrolled bleeding and inadequate inhibitor suppression by IST for 1 week. Complete remission (CR) was defined as FVIII:C normalization, no active bleeding after 24-hour discontinuation of hemostatic agents, and negative inhibitor ( < 0.4 BU/mL) when using prednisolone < 15 mg/day.
Results: An initial inhibitor titer of 179.2 BU/mL was decreased to 141.6-148.8 BU/mL, while FVIII:C of < 1 IU/dL modestly elevated to 2.9-4.6 IU/dL and the hematomas expanded during the first week of treatment. The adjunctive daratumumab therapy could rapidly suppress FVIII inhibitors to the first negative titer and induce CR within 33 and 63 days, respectively. (Figure 1). All BAs were discontinued within 23 days. After prednisolone tapering-off, FVIII inhibitor remained undetectable until 13 months of follow-up. No infectious complications occurred despite transient hypogammaglobulinemia and CD19+ B-cell depletion post-daratumumab (Table 1).
Conclusion(s): Short-course daratumumab combined with standard IST yields a dramatic decline of anti-FVIII autoantibody titers and safe CR achievement in an AHA patient with poor prognostic markers.
To cite this abstract in AMA style:Moonla C, Polprasert C, Krittikarux S, Krajibthong S, Chajuwan T, Sukperm A, Akkawat B, Rojnuckarin P, Uaprasert N. Daratumumab as an Adjunctive Therapy for Acquired Hemophilia A with Poor Prognostic Markers [abstract]. https://abstracts.isth.org/abstract/daratumumab-as-an-adjunctive-therapy-for-acquired-hemophilia-a-with-poor-prognostic-markers/. Accessed September 27, 2022.
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