MedUni Vienna: New approach to personalised therapy following kidney transplantation
Study identifies blood-based biomarker to personalise treatment of antibody-mediated rejection after kidney transplantation.
An international research team led by MedUni Vienna has, for the first time, used the blood-based biomarker donor-derived cell-free DNA (dd-cfDNA) to individualise treatment for antibody-mediated rejection (AMR) following kidney transplantation. The study demonstrates that dd-cfDNA can detect transplant injury and guide the need for additional treatment, while long-term therapy with the CD38 antibody felzartamab was shown to keep rejection activity under control in many patients. The findings have been published in The Lancet Regional Health – Europe.
Antibody-mediated rejection is one of the leading causes of kidney transplant failure. Until now, disease activity has primarily been monitored through tissue biopsies. The dd-cfDNA biomarker offers a less invasive alternative by measuring DNA fragments released from the transplanted organ into the bloodstream when damage occurs. Elevated dd-cfDNA levels may therefore indicate active rejection.
The study followed a previously published Phase 2 trial investigating the efficacy and safety of felzartamab. Since rejection activity frequently returned after treatment ended, researchers examined whether prolonged therapy guided by monthly dd-cfDNA measurements could improve disease control.
Eleven patients with persistent or recurrent antibody-mediated rejection were monitored for twelve months. Following six months of fixed treatment, therapy during the subsequent six months was individualised based on dd-cfDNA levels. Additional felzartamab doses were administered only when biomarker levels exceeded predefined thresholds, indicating renewed transplant injury.
The biomarker responded sensitively to treatment. Following felzartamab administration, dd-cfDNA levels typically declined and remained low in many patients. During the biomarker-guided treatment phase, some participants required only two additional infusions over six months, highlighting considerable differences in individual treatment needs. Inflammation of small blood vessels within the transplanted kidney, a key indicator of antibody-mediated rejection, decreased significantly, and after 52 weeks seven of the eleven patients no longer showed inflammatory activity. Molecular analyses also demonstrated a marked reduction in disease activity, while kidney function remained stable throughout the study.
The researchers conclude that antibody-mediated rejection often represents a chronic process that may benefit from prolonged treatment. They also provide the first evidence that biomarker-guided therapy using donor-derived cell-free DNA could enable earlier detection of transplant injury and more personalised treatment strategies. Larger controlled clinical trials will be required to confirm these findings.