Kidney Week

Abstract: TH-PO806

Use of Donor-Derived Cell-Free DNA and Gene Expression Profiling to Facilitate Belatacept Monotherapy in Kidney Transplant Recipients

Session Information

• Transplantation: Clinical - 2
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 2102 Transplantation: Clinical

Authors

• Wojciechowski, David, The University of Texas Southwestern Medical Center, Dallas, Texas, United States

David Wojciechowski, DO

• Salcedo Betancourt, Juan David, The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Juan David Salcedo Betancourt, MD

• Marsh, Morgan, The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Morgan Marsh

• Feizpour, Cyrus, Indiana University School of Medicine, Indianapolis, Indiana, United States

Cyrus Feizpour, MD

• Han, Hwarang Stephen, The University of Texas at Austin, Austin, Texas, United States

Hwarang Stephen Han, DO

• Lakhani, Laila S., The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Laila S. Lakhani, MD

• Levea, Swee-Ling, The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Swee-Ling Levea, MD

• Anderson, Lee E., The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Lee E. Anderson, MD, MPH

Background

Donor-derived cell-free DNA (AlloSure) levels <1.0 % and gene expression profiling (AlloMap) score <11.5 help discriminate immune quiescence from acute rejection. We investigated their utility in weaning to belatacept monotherapy.

Methods

Between December 2022 and April 2024, we enrolled adult kidney recipients on belatacept immunosuppression with stable renal function (eGFR >40 mL/min/1.73m2) and absent Donor-Specific Antibodies (DSA) into a 12-month prospective, single-center, interventional pilot study. AlloSure, AlloMap, serum creatinine, spot urine protein, and DSA were measured at monthly infusion visits. Patients deemed clinically stable (eGFR <20% lower than baseline, absence of biopsy-proven rejection) and immune quiescent (absence of de novo DSA, AlloMap <11.5, AlloSure <1.0 % or >0.5% without a change >61% from baseline) underwent immunosuppression tapering. Outcomes included biopsy-proven rejection, allograft/patient survival, change in eGFR, proteinuria or de-novo DSA development, and percentage of patients weaned to belatacept monotherapy.

Results

We analyzed the first 19 patients who completed at least 6 months of follow-up. Subjects were predominantly male (n=14) with a mean age of 56 years. Mean eGFR in mL/min/1.73m2 was 72.84 ± 19.04 SD at enrollment and 70.47 ± 18.59 SD at 6 months. The most common agents used with belatacept were prednisone + mycophenolate (n = 16), prednisone + everolimus (n = 2) or sirolimus (n=1). Mean AlloSure and AlloMap throughout were 0.27% ± 0.25 and 11.29 ± 1.99 respectively. 5 patients (26%) were weaned off prednisone, and 2 were weaned entirely off prednisone and mycophenolate. There was 100% patient and graft survival, with no biopsy-proven rejection, nephrotic proteinuria, or DSA development.

Conclusion

Despite having AlloSure <1%, the mean AlloMap score was above the reported threshold shown to discriminate rejection from quiescence. We hypothesize that patients on belatacept-based immunosuppression have higher AlloMap scores even if immune quiescent, as prior studies primarily included patients on tacrolimus-based immunosuppression. Higher cutoffs may be necessary for this population. Investigation is ongoing to test this hypothesis in our cohort.

Funding

• Commercial Support – CareDx