达拉单抗单药治疗作为心脏移植前的脱敏策略。

Ruben J Crespo-Diaz,Adrian J daSilva-deAbreu,Andrew N Rosenbaum,Stacy A Bernard,Manish J Gandhi,Shaji Kumar,Taxiarchis Kourelis,Atta Behfar,Alfredo L Clavell,Shannon M Dunlay,Robert P Frantz,Sudhir S Kushwaha,Naveen L Pereira,Yee Weng Wong,Richard C Daly,Philip J Spencer,Mauricio A Villavicencio Theoduloz,Barry A Boilson
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引用次数: 0

摘要

人类白细胞抗原(HLA)致敏是许多患者移植的重要障碍。Daratumumab已被证明在多发性骨髓瘤中的安全性和耐受性。我们假设daratumumab单药治疗对于等待心脏移植的高度敏感患者可能是一种有效且安全的脱敏策略。目的:本试验的主要终点是达拉单抗在降低HLA抗体方面的作用范围。次要终点包括供体特异性抗体的存在,细胞和抗体介导的排斥反应(AMR)的发生率和心脏同种异体移植功能。方法连续6例高致敏患者,通过单抗原珠测定,平均荧光强度(MFI)阈值> 4000计算出面板反应性抗体bbb50 %。其中3例完成了8周的达拉单抗治疗。HLA抗体MFI值在1万以下的被认为不适合供体。所有患者每周接受1,800 mg daratumumab和30,000单位透明质酸酶皮下注射,计划总共8周。结果HLAⅰ类和ⅱ类抗体在心脏移植时明显降低。Daratumumab耐受性良好,无任何严重不良事件。到本文发表时,6例患者中有5例已成功移植。所有患者均未经历AMR并维持正常的心脏移植功能。结论sdaratumumab单药治疗可能是一种安全有效的脱敏策略,适用于适合心脏移植的高度敏感患者,且病情严重,不适合其他脱敏策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Daratumumab monotherapy as a desensitization strategy prior to cardiac transplantation.
BACKGROUND Human leukocyte antigen (HLA) sensitization is a significant barrier to transplantation for many patients. Daratumumab has proven safety and tolerability in multiple myeloma. We hypothesized that daratumumab monotherapy could be an effective and safe desensitization strategy in highly sensitized patients awaiting cardiac transplantation. OBJECTIVES The primary end-point of this trial was the scope of daratumumab in lowering HLA antibodies. Secondary end-points included presence of donor-specific antibody, incidence of cellular and antibody-mediated rejection (AMR) and cardiac allograft function. METHODS Six consecutive highly sensitized patients were enrolled who had a calculated panel reactive antibody >50% using a mean fluorescence intensity (MFI) threshold >4,000 through a single antigen bead assay. Three completed the full 8 weeks of daratumumab therapy. HLA antibodies with MFI >10,000 were considered unacceptable for donor offers. All patients received weekly doses of 1,800 mg daratumumab and 30,000 units hyaluronidase subcutaneously for a planned total of 8 weeks. RESULTS There was a significant reduction in HLA class I and class II antibodies by the time of heart transplantation. Daratumumab was well tolerated and without any serious adverse events. By the time of this publication, 5 of the total of 6 patients enrolled have been successfully transplanted. None of the patients enrolled experienced AMR and maintain normal cardiac allograft function. CONCLUSIONS Daratumumab monotherapy may be a safe and effective desensitization strategy in highly sensitized patients who are otherwise eligible for heart transplantation and considered too ill for other desensitization strategies.
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