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Kidney Week

Abstract: TH-OR107

Treatment of Subclinical Antibody-Mediated Rejection and Isolated Microvascular Inflammation with Daratumumab Guided by Donor-Derived Cell-Free DNA

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Acevedo Rodriguez, Jessica Edith, John H Stroger Jr Hospital of Cook County, Chicago, Illinois, United States
  • Campana, Otto, Hospital General Macas, Macas, Ecuador
  • Rodriguez Reyes, Leonardo, The University of Texas Rio Grande Valley, Harligen, Texas, United States
  • Pozo Garcia, Leonardo, Arizona Kidney Disease and Hypertension Center, Tucson, Arizona, United States
Background

Anti-CD38 monoclonal antibody daratumumab is emerging as a treatment option for antibody-mediated rejection (AMR) and isolated microvascular inflammation (MVI). Evidence of its role in the early stages of allograft injury is still developing. Donor-derived cell-free DNA (dd-cfDNA) has an established role in the early detection of subclinical rejection phenotypes and in monitoring trends after treatment of biopsy-proven acute rejection (BPAR), providing a real-time assessment of therapeutic response.

Methods

A total of seven kidney transplant recipients with biopsy-proven subclinical AMR and MVI were included, identified after an elevated dd-cfDNA alone prompted biopsy. Clinical parameters and dd-cfDNA levels were assessed at baseline and at 3-months post-treatment. Treatment was deemed successful if the fraction of dd-cfDNA at 3-months decreased to less than 1% or showed a 50% decrease from baseline.

Results

The mean baseline serum creatinine was 1.04 mg/dL, the mean baseline UPCR was 115 mg/g, and dd-cfDNA was elevated in all patients (range 1.09% – 6.69%). After treatment with daratumumab, dd-cfDNA decreased significantly from baseline to 3-month follow-up (mean 3.96% vs 0.61%; p=0.0015), while serum creatinine and proteinuria remained stable (mean creatinine 1.02 mg/dL; mean UPCR 111 mg/g).

Conclusion

Treatment of subclinical AMR and MVI with daratumumab was associated with a significant decrease in dd-cfDNA after 3 months. A larger double-blind randomized controlled trial will be needed to demonstrate the utility of dd-cfDNA for long-term monitoring, as well as its correlation with histology.