Donor-Derived Cell-Free DNA as a Companion Biomarker for AMR Treatment With Daratumumab: Case Series.

IF 2.7 3区医学 Q1 SURGERY

Transplant International Pub Date : 2024-08-01 eCollection Date: 2024-01-01 DOI:10.3389/ti.2024.13213

Bilgin Osmanodja, Aylin Akifova, Klemens Budde, Michael Oellerich, Julia Beck, Kirsten Bornemann-Kolatzki, Ekkehard Schütz, Joachim Velden, Claudia Lehmann, Bastian Malte Krüger, Anette Bachmann, Jan Kowald

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引用次数: 0

Abstract

Antibody-mediated rejection (AMR) is among the most frequent causes for graft loss after kidney transplantation. While there are no approved therapies, several case reports with daratumumab and the very recent phase 2 trial of felzartamab in AMR have indicated the potential efficacy of therapeutic interventions targeting CD38. Donor-derived cell-free DNA (dd-cfDNA) is an emerging biomarker with injury-specific release and a short half-life, which could facilitate early diagnosis of AMR and monitoring of treatment response. We describe two cases of patients with chronic active AMR, who were treated with monthly daratumumab infusions, and in whom donor-derived cell-free DNA (dd-cfDNA) was measured longitudinally to monitor treatment response. In both patients, daratumumab treatment led to stabilization of kidney function parameters, a strong decline of dd-cfDNA below the previously established threshold for rejection, and partial or complete histologic resolution of AMR activity. Our case series suggests that dd-cfDNA may be a useful companion biomarker for longitudinal monitoring of anti-CD38 treatment in patients with AMR.

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作为达拉单抗治疗急性髓系白血病的辅助生物标记物的供体来源细胞游离 DNA：病例系列。

抗体介导的排斥反应（AMR）是肾移植后移植物丧失的最常见原因之一。虽然目前还没有获得批准的治疗方法，但达拉单抗的几个病例报告和最近进行的非扎他单抗治疗 AMR 的 2 期试验表明，针对 CD38 的治疗干预措施具有潜在的疗效。供体源性细胞游离 DNA（dd-cfDNA）是一种新兴的生物标记物，具有损伤特异性释放和短半衰期的特点，有助于 AMR 的早期诊断和治疗反应的监测。我们描述了两例慢性活动性AMR患者，他们每月接受达拉土单抗输注治疗，并对供体细胞游离DNA（dd-cfDNA）进行纵向测量以监测治疗反应。在这两名患者中，达拉土单抗治疗导致肾功能参数趋于稳定，dd-cfDNA大幅下降，低于先前确定的排斥阈值，AMR活动在组织学上部分或完全消失。我们的病例系列表明，dd-cfDNA可能是纵向监测AMR患者抗CD38治疗的有用辅助生物标记物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Transplant International 医学-外科

CiteScore

4.70

自引率

6.50%

发文量

211

审稿时长

3-8 weeks

期刊介绍： The aim of the journal is to serve as a forum for the exchange of scientific information in the form of original and high quality papers in the field of transplantation. Clinical and experimental studies, as well as editorials, letters to the editors, and, occasionally, reviews on the biology, physiology, and immunology of transplantation of tissues and organs, are published. Publishing time for the latter is approximately six months, provided major revisions are not needed. The journal is published in yearly volumes, each volume containing twelve issues. Papers submitted to the journal are subject to peer review.