本文由小咖机器人翻译整理

期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2400763

摘要内容如下：

背景

抗体介导的排斥反应是肾移植失败的主要原因。靶向CD38抑制同种异体抗体和自然杀伤（NK）细胞引起的移植物损伤可能是一种治疗选择。

方法

在这项2期、双盲、随机、安慰剂对照试验中，我们将移植后至少180天发生抗体介导的排斥反应的患者分为两组，一组接受9次CD38单克隆抗体felzartamab（剂量为16 mg/kg体重）输注，另一组接受安慰剂，为期6个月，然后是6个月的观察期。主要结果是felzartamab的安全性和副作用。关键的次要结果是24周和52周的肾活检结果、供体特异性抗体水平、外周NK细胞计数和供体来源的无细胞DNA水平。

结果

共有22名患者接受了随机分组（11名接受felzartamab，11名接受安慰剂）。从移植到纳入试验的中位时间为9年。Felzartamab组有8例患者出现轻度或中度输液反应。严重不良事件在felzartamab组和安慰剂组分别为1例和4例；安慰剂组中有1名患者发生移植物丢失。24周后，felzartamab组（11例患者中有9例[82%]）比安慰剂组（10例患者中有2例[20%]）形态学抗体介导的排斥反应消退的频率更高，差异为62个百分点（95%可信区间[CI]，19-100），风险比为0.23（95%可信区间[CI]，0.06-0.83）。felzartamab组的微血管炎症评分中位数低于安慰剂组（0 vs.2.5），平均差异为-1.95（95%CI，-2.97至-0.92）。反映抗体介导的排斥反应概率的分子评分（0.17 vs.0.77）和供体来源的无细胞DNA水平（0.31%vs.0.82%）也较低。在第52周，9名对felzartamab有反应的患者中有3名报告抗体介导的排斥反应复发，分子活性和生物标志物水平增加至基线水平。

结论

Felzartamab在抗体介导的排斥反应患者中具有可接受的安全性和副作用。（由MorphoSys和Human Immunology Biosciences资助；ClinicalTrials.gov编号，NCT05021484；和Eudract号，2021-000545-40）。

英文原文如下：

Abstracts

BACKGROUND  Antibody-mediated rejection is a leading cause of kidney-transplant failure. The targeting of CD38 to inhibit graft injury caused by alloantibodies and natural killer (NK) cells may be a therapeutic option.

METHODS  In this phase 2, double-blind, randomized, placebo-controlled trial, we assigned patients with antibody-mediated rejection that had occurred at least 180 days after transplantation to receive nine infusions of the CD38 monoclonal antibody felzartamab (at a dose of 16 mg per kilogram of body weight) or placebo for 6 months, followed by a 6-month observation period. The primary outcome was the safety and side-effect profile of felzartamab. Key secondary outcomes were renal-biopsy results at 24 and 52 weeks, donor-specific antibody levels, peripheral NK-cell counts, and donor-derived cell-free DNA levels.

RESULTS  A total of 22 patients underwent randomization (11 to receive felzartamab and 11 to receive placebo). The median time from transplantation until trial inclusion was 9 years. Mild or moderate infusion reactions occurred in 8 patients in the felzartamab group. Serious adverse events occurred in 1 patient in the felzartamab group and in 4 patients in the placebo group; graft loss occurred in 1 patient in the placebo group. After week 24, resolution of morphologic antibody-mediated rejection was more frequent with felzartamab (in 9 of 11 patients [82%]) than with placebo (in 2 of 10 patients [20%]), for a difference of 62 percentage points (95% confidence interval [CI], 19 to 100) and a risk ratio of 0.23 (95% confidence interval [CI], 0.06 to 0.83). The median microvascular inflammation score was lower in the felzartamab group than in the placebo group (0 vs. 2.5), for a mean difference of -1.95 (95% CI, -2.97 to -0.92). Also lower was a molecular score reflecting the probability of antibody-mediated rejection (0.17 vs. 0.77) and the level of donor-derived cell-free DNA (0.31% vs. 0.82%). At week 52, the recurrence of antibody-mediated rejection was reported in 3 of 9 patients who had a response to felzartamab, with an increase in molecular activity and biomarker levels toward baseline levels.

CONCLUSIONS  Felzartamab had acceptable safety and side-effect profiles in patients with antibody-mediated rejection. (Funded by MorphoSys and Human Immunology Biosciences; ClinicalTrials.gov number, NCT05021484; and EUDRACT number, 2021-000545-40.).

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