Weisinger Julia, Bouzid Raïda, Ranta Dana, Woaye-Hune Pascal, Cohen-Aubart Fleur, Gaible Clotilde, Marjanovic Zora, Corre Elise, Joly Anne-Christine, Baylatry Minh-Tam, Joly Berangère S, Veyradier Agnès, Coppo Paul
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.
INSERM Unité Mixte de Recherche (UMRS) 1138, Centre de Recherche des Cordeliers, Paris, France.
Br J Haematol. 2024 Nov;205(5):1951-1958. doi: 10.1111/bjh.19752. Epub 2024 Sep 4.
The 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.
对于对B细胞耗竭单克隆抗体利妥昔单抗不耐受或难治的免疫介导性血栓性血小板减少性紫癜（iTTP）患者，其免疫抑制治疗仍存在争议。达雷妥尤单抗是一种靶向CD38的浆细胞定向单克隆抗体，是一种治疗选择，但相关数据较少。法国血栓性微血管病参考中心对接受达雷妥尤单抗治疗的iTTP患者进行了一项全国性调查。共确定了7例患者的9次治疗情况。治疗用于含血小板反应蛋白基序的解聚素样金属蛋白酶13（ADAMTS13）复发的患者，这些患者在其他方面有临床反应（N = 8），或在利妥昔单抗不耐受后的疾病急性期（N = 1）。患者之前接受的治疗方案中位数为3种。在给予达雷妥尤单抗后，8例患者的ADAMTS13活性有所改善，其中3例ADAMTS13恢复正常。3例患者出现ADAMTS13复发；2例再次使用达雷妥尤单抗治疗成功。未达到ADAMTS13无复发生存的中位数；12个月的ADAMTS13无复发生存率为56%。5例出现了与达雷妥尤单抗相关的不良事件，所有病例均为非严重的输液相关反应。这些结果表明，对于对利妥昔单抗不耐受或难治的iTTP患者，达雷妥尤单抗可能是一种有效的治疗选择。
