Pham Christine, Pierce Brett J, Nguyen Duc T, Graviss Edward A, Huang Howard J
Department of Pharmacy, Houston Methodist Hospital, Houston, TX.
Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX.
Transplant Direct. 2021 Mar 16;7(4):e680. doi: 10.1097/TXD.0000000000001131. eCollection 2021 Apr.
Data supporting the use of carfilzomib (CFZ) for treatment of antibody-mediated rejection (AMR) in lung transplantation in combination with plasmapheresis and intravenous immunoglobulin suggest positive outcomes through donor-specific antibody (DSA) depletion or conversion to noncomplement-activating antibodies. Herein, we describe our center's experience treating AMR with CFZ.
All patients treated with CFZ for AMR from 2014 to 2019 were included. The primary outcome was a positive response to CFZ was defined as: (1) loss of DSA C1q-fixing ability after last CFZ dose; (2) clearance of de novo DSA; or (3) decrease in de novo DSA mean fluorescence intensity of >3000.
Twenty-eight patients with 31 AMR episodes were treated with CFZ. A positive response was observed in 74.4% of AMR episodes and 82.1% of patients. This response was driven by loss of complement 1q fixation (70.6%), elimination of class I DSAs (78.6%), and reduction in both classes I (median 2815, 79.5% reduction from baseline) and II DSA mean fluorescence intensity (3171, 37.1%).
CFZ shows potential for ameliorating AMR; however, additional studies are needed to define optimal time of administration.
有数据支持将卡非佐米（CFZ）与血浆置换和静脉注射免疫球蛋白联合用于治疗肺移植中抗体介导的排斥反应（AMR），表明通过供体特异性抗体（DSA）清除或转化为非补体激活抗体可取得积极效果。在此，我们描述了我们中心使用CFZ治疗AMR的经验。
纳入2014年至2019年所有接受CFZ治疗AMR的患者。主要结局对CFZ的阳性反应定义为：（1）最后一剂CFZ后DSA C1q结合能力丧失；（2）新生DSA清除；或（3）新生DSA平均荧光强度降低>3000。
28例患者发生31次AMR发作，接受了CFZ治疗。74.4%的AMR发作和82.1%的患者观察到阳性反应。这种反应是由补体1q结合丧失（70.6%）、I类DSA消除（78.6%）以及I类（中位数2815，较基线降低79.5%）和II类DSA平均荧光强度降低（3171，降低37.1%）驱动的。
CFZ显示出改善AMR的潜力；然而，需要进一步研究来确定最佳给药时间。
