PB1002 - Daratumumab as an Adjunctive Therapy for Acquired Hemophilia A with Poor Prognostic Markers

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Chatphatai Moonla, MD MSc

Instructor
Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital
Bangkok, Krung Thep, Thailand

Co-Author(s)

CP

Chantana Polprasert

Associate Professor
Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital
Bangkok, Krung Thep, Thailand
SK

San Krittikarux

Hematologist
Department of Medicine, Sakaeo Crown Prince Hospital
Sa Kaeo, Sa Kaeo, Thailand
SK

Suphattharachai Krajibthong

Hematologist
Department of Medicine, Hua Hin Hospital
Hua Hin, Prachuap Khiri Khan, Thailand
TC

Thunyamon Chajuwan

Hematologist
Department of Medicine, Sunpasitthiprasong Hospital
Ubon Ratchathani, Ubon Ratchathani, Thailand
AS

Autcharaporn Sukperm

Clinical Laboratory Scientist
Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital
Bangkok, Krung Thep, Thailand
BA

Benjaporn Akkawat

Technician
Chulalongkorn University
Bangkok, Krung Thep, Thailand
PR

Ponlapat Rojnuckarin

Professor
Excellence Center in Translational Hematology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Bangkok, Krung Thep, Thailand
Noppacharn Uaprasert, MD

Associate Professor
Excellence Center in Translational Hematology, Division of Hematology, Faculty of Medicine, Chulalongkorn University
Bangkok, Krung Thep, Thailand

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.