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

Transpl Int. 2024 Aug 1:37:13213. doi: 10.3389/ti.2024.13213. eCollection 2024.

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.

Keywords: antibody-mediated rejection; biomarker; daratumumab; donor-derived cell-free DNA; kidney transplantation.

Publication types

  • Case Reports

MeSH terms

  • ADP-ribosyl Cyclase 1
  • Adult
  • Antibodies, Monoclonal* / therapeutic use
  • Biomarkers* / blood
  • Cell-Free Nucleic Acids* / blood
  • Female
  • Graft Rejection* / drug therapy
  • Humans
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Tissue Donors

Substances

  • daratumumab
  • Cell-Free Nucleic Acids
  • Antibodies, Monoclonal
  • Biomarkers
  • ADP-ribosyl Cyclase 1

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The authors declare that this study received funding from Oncocyte. Specifically, laboratory testing of dd-cfDNA was sponsored by Oncocyte. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.