Outcomes at 3 years posttransplant in imlifidase-desensitized kidney transplant patients.
Outcomes at 3 years posttransplant in imlifidase-desensitized kidney transplant patients.
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DOI：
10.1111/ajt.16754
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发表时间：
2021-12
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Imlifidase是一种半胱氨酸蛋白酶，可特异性切割IgG，在给药后数小时内抑制Fc介导的效应器功能。Imlifidase可将与潜在供体（T细胞、B细胞或两者）交叉配型阳性的患者转化为阴性，从而使之前HLA不相容的供体-受体对之间能够进行移植。迄今为止，在4项单组、开放标签、II期研究中，39例交叉配型阳性患者在肾移植前接受了伊立非达酶治疗。3年时，AMR+与AMR-患者的死亡删失同种异体移植物生存率分别为93%与77%，患者生存率分别为85%与94%，平均eGFR分别为49 ml/min/1.73 m2与61 ml/min/1.73 m2。AMR的发生率为38%，大多数事件发生在移植后第一个月内。对cPRA ≥ 99.9%且被视为高度致敏且不太可能接受移植的患者进行的亚组分析显示，接受交叉配型阳性、死亡供体移植的患者生存率、移植物生存率和eGFR相似，但AMR率较高。这些数据表明，接受伊立非达酶激活的同种异体移植物的受者长达3年的结局和安全性与接受HLA不相容移植的其他高度致敏患者的结局相当。因此，在对成功肾移植有显著免疫屏障的患者中，伊立非达酶是促进移植的有效选择。临床试验：ClinicalTrials.gov（NCT 02790437），EudraCT编号：2016 - 002064 - 13。在肾移植前接受伊立非达酶的交叉配型阳性患者的患者生存期、移植物生存期、eGFR和急性抗体介导的排斥反应发生率与其他接受HLA不相容移植的高度致敏患者相当。参见Schinstock和Tambur在3825页的社论。
Imlifidase is a cysteine proteinase which specifically cleaves IgG, inhibiting Fc‐mediated effector function within hours of administration. Imlifidase converts a positive crossmatch to a potential donor (T cell, B cell, or both), to negative, enabling transplantation to occur between previously HLA incompatible donor‐recipient pairs. To date, 39 crossmatch positive patients received imlifidase prior to a kidney transplant in four single‐arm, open‐label, phase 2 studies. At 3 years, for patients who were AMR+ compared to AMR−, death‐censored allograft survival was 93% vs 77%, patient survival was 85% vs 94%, and mean eGFR was 49 ml/min/1.73 m2 vs 61 ml/min/1.73 m2, respectively. The incidence of AMR was 38% with most episodes occurring within the first month post‐transplantation. Sub‐analysis of patients deemed highly sensitized with cPRA ≥ 99.9%, and unlikely to be transplanted who received crossmatch‐positive, deceased donor transplants had similar rates of patient survival, graft survival, and eGFR but a higher rate of AMR. These data demonstrate that outcomes and safety up to 3 years in recipients of imlifidase‐enabled allografts is comparable to outcomes in other highly sensitized patients undergoing HLA‐incompatible transplantation. Thus, imlifidase is a potent option to facilitate transplantation among patients who have a significant immunologic barrier to successful kidney transplantation. Clinical Trial: ClinicalTrials.gov (NCT02790437), EudraCT Number: 2016‐002064‐13. Crossmatch positive patients who received imlifidase prior to kidney transplantation enjoy comparable patient survival, graft survival, eGFR and rates of acute antibody mediated rejection to other highly sensitized patients undergoing HLA‐incompatible transplantation. See Schinstock and Tambur's editorial on page 3825.
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