Efficacy and safety of daratumumab in multiresistant immune‐mediated thrombotic thrombocytopenic purpura

Author:

Weisinger Julia1ORCID,Bouzid Raïda12,Ranta Dana3,Woaye‐Hune Pascal4,Cohen‐Aubart Fleur5,Gaible Clotilde6,Marjanovic Zora1ORCID,Corre Elise1,Joly Anne‐Christine7,Baylatry Minh‐Tam7,Joly Berangère S.128,Veyradier Agnès128,Coppo Paul12ORCID

Affiliation:

1. Service d'hématologie, Centre de Référence des Microangiopathies Thrombotiques (CNR‐MAT) Hôpital Saint Antoine, Assistance Publique‐Hôpitaux de Paris and Sorbonne Université (AP‐HP.6) Paris France

2. INSERM Unité Mixte de Recherche (UMRS) 1138 Centre de Recherche des Cordeliers Paris France

3. Service d'Hématologie Centre Hospitalier Universitaire de Nancy Nancy France

4. Centre Hospitalier Départemental Vendée La Roche sur Yon France

5. Départment de Médecine Interne 2 Hôpital Pitié‐Salpêtrière, Assistance Publique‐Hôpitaux de Paris and Sorbonne Université (AP‐HP.6) Paris France

6. Néphrologie et Transplantation d'organes Centre Hospitalier Universitaire Rangueil Toulouse France

7. Pharmacie Hôpital Saint‐Antoine, Assistance Publique‐Hôpitaux de Paris Paris France

8. Service d'Hématologie Biologique Hôpital Lariboisière, Assistance Publique‐Hôpitaux de Paris Nord, Université Paris Cité Paris France

Abstract

SummaryThe immunosuppressive treatment of immune‐mediated thrombotic thrombocytopenic purpura (iTTP) in patients with intolerance or refractoriness to the B‐cell depleting monoclonal antibody rituximab remains debated. Daratumumab, a plasma cell‐directed monoclonal antibody targeting CD38, represents a therapeutic option, but data are scarce. The French Thrombotic Microangiopathies Reference Center conducted a nationwide survey on iTTP patients treated with daratumumab. Nine episodes from seven patients were identified. Treatment was administered for A Disintegrin And Metalloproteinase with ThromboSpondin‐1 motifs, 13th member (ADAMTS13) relapses while patients were otherwise in clinical response (N = 8), or during the acute phase of the disease following rituximab intolerance (N = 1). Patients have received a median of three previous therapeutic lines. ADAMTS13 activity improved in eight cases following daratumumab administration, including three cases where ADAMTS13 normalized. ADAMTS13 relapses occurred in three patients; in two cases, retreatment with daratumumab was successful. Median ADAMTS13 relapse‐free survival was not reached; 12‐month ADAMTS13 relapse‐free survival was 56%. Daratumumab‐related adverse events occurred in five cases and were non‐severe infusion‐related reactions in all cases. These results suggest that daratumumab may be an effective treatment option for iTTP patients with intolerance or refractoriness to rituximab.

Funder

European Commission

Publisher

Wiley

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