(Vienna, 15 July 2026) An international research team led by MedUni Vienna has, for the first time, used a blood-based biomarker in a study to individualise treatment for antibody-mediated rejection following kidney transplantation. The results show that so-called donor-derived cell-free DNA (dd-cfDNA) could be used to detect damage to the transplant and the need for further treatment. At the same time, the data confirm that long-term treatment with the active substance felzartamab can keep the activity of the rejection reaction under control in many patients. The study has recently been published in the journal The Lancet Regional Health – Europe.
Antibody-mediated rejection (AMR) is one of the leading causes of loss of function in transplanted kidneys. Until now, disease activity has primarily been assessed by taking tissue samples from the organ. The dd-cfDNA biomarker could offer a new and significantly less invasive approach: it measures DNA fragments originating from the transplanted organ, which are released into the blood in greater quantities when the organ is damaged. Elevated levels may therefore indicate an active rejection reaction.
The study now presented follows on from a previously published randomised, placebo-controlled Phase 2 trial on the efficacy and safety of the CD38 antibody felzartamab. After it had been shown that rejection activity often increases again following the end of treatment with this active substance, the research team investigated whether prolonged therapy and treatment management based on dd-cfDNA levels would be effective.
Varying treatment requirements
To this end, eleven patients with persistent or recurrent rejection reactions were monitored over a period of twelve months. Following a six-month treatment phase with a fixed regimen, therapy was tailored individually for a further six months based on monthly dd-cfDNA measurements. Additional doses of felzartamab were administered only when blood levels exceeded certain thresholds, indicating renewed damage to the transplant.
The results in detail: The measured dd-cfDNA levels responded sensitively to treatment. Following administration of felzartamab, they typically declined and remained low in many patients. During the biomarker-guided phase, some participants received only two additional infusions within six months, with marked differences observed between individual patients. This suggests that treatment requirements can vary greatly from person to person. At the same time, inflammation of small blood vessels in the transplant – an important marker of antibody-mediated rejection – decreased significantly. After 52 weeks, seven out of eleven patients no longer showed any such inflammatory activity. Molecular analyses of the transplant tissue also indicated a marked reduction in disease activity. Kidney function remained stable throughout the entire observation period.
Further studies needed
"Our findings support the hypothesis that antibody-mediated rejection reactions are often a chronic process and could benefit from longer-term treatment," said lead author Katharina Mayer (Department of Medicine III). "At the same time, our study shows for the first time that treatment for antibody-mediated rejection can be personalised using a biomarker. Donor-derived cell-free DNA could help to detect the disease at an early stage and target treatments more effectively in future," added study leader Georg A. Böhmig (Department of Medicine III). The authors emphasise that the findings need to be confirmed in larger controlled trials. However, the data provide initial evidence of the potential of donor-derived cell-free DNA for personalised treatment strategies following kidney transplants.
Publication: The Lancet Regional Health – Europe
Prolonged CD38 targeting with felzartamab in antibody-mediated kidney transplant rejection: a biomarker-guided open-label phase 2 extension.
Katharina A. Mayer, Matthias Diebold, Eva V. Schrezenmeier, Philip F. Halloran, Susanne Haindl, Martina Schatzl, Aylin Akifova, Daniela M. Allmer, Sabine Schranz, Nicolas Kozakowski, Johannes Kläger, Kerstin Amann, Julia Beck, Ekkehard Schütz, Maarten Naesens, Alexandre Loupy, Marc Raynaud, Irene Görzer, Hannes Vietzen, Gordon Ingle, Donna L. Flesher, Uptal D. Patel, Fabian Halleck, Irene Graf, Bernd Jilma, Klemens Budde, Georg A. Böhmig.
https://doi.org/10.1016/j.lanepe.2026.101768