Abstract: SA-PO1054
Use of Donor-Derived Cell-Free DNA and Gene Expression Profiling to Facilitate Belatacept Monotherapy in Kidney Transplant Recipients
Session Information
- Transplantation: Clinical - II
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Salcedo Betancourt, Juan David, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Marsh, Morgan, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Feizpour, Cyrus, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Han, Hwarang Stephen, The University of Texas at Austin UT Health Austin, Austin, Texas, United States
- Lakhani, Laila S., The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Levea, Swee-Ling, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Wojciechowski, David, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
Background
Studies have demonstrated that a donor-derived cell free DNA (dd-cfDNA; AlloSure) >1.0% can be used as a biomarker of allograft rejection. A gene expression profiling (AlloMap) threshold of 11.5 has shown to discriminate rejection from immune quiescence. We aimed to investigate their utility in weaning to Belatacept monotherapy immunosuppression.
Methods
Between December 2022 and April 2023, we enrolled adult kidney recipients on Belatacept immunosuppression with stable renal function (eGFR > 40 mL/min/1.73 m2) and negative Donor-Specific Antibodies (DSA) into a prospective, single-center, observational pilot study. Patients with acute rejection episodes were excluded. AlloSure, AlloMap, serum creatinine, urine protein, and DSA were measured at monthly Belatacept infusion visits. Patients deemed immune quiescent underwent immunosuppression tapering. Outcomes were: 1) Incidence of biopsy-proven acute rejection and 2) allograft and patient survival, change in eGFR, development of proteinuria or de-novo DSA.
Results
We analyzed the first 11 patients who completed 6 months of follow-up. Subjects were predominantly male (n=7), with a mean age of 57 years, mean eGFR of 65.1 mL/min/1.73m2 ± 14.7 SD on enrollment, and 67 mL/min/1.73m2 ± 15.0 SD at the 6 months follow up. The most common agents used with Belatacept were Prednisone and Mycophenolate (n = 9) followed by Prednisone and Everolimus (n = 2). Mean AlloSure and AlloMap values throughout follow up were 0.20% ± 0.05 and 11.5 ± 1.4 respectively. 5 patients (45%) were weaned off steroids; no subjects were weaned entirely off mycophenolate or everolimus due to an AlloMap over the threshold. There was 100% patient and graft survival, with no cases of biopsy-proven rejection, proteinuria or DSA development.
Conclusion
Despite having AlloSure <1%, the mean AlloMap score was above the reported treshold shown to discriminate rejection from quiescence. We hypothesize that patients on Belatacept-based immunosuppression regimen have a higher baseline AlloMap levels even if immune quiescent, as prior AlloMap studies primarily included patients treated with tacrolimus-based immunosuppression. Higher cutoffs may be necessary for these patients. Investigation is ongoing to assess this hypothesis in our cohort.
Funding
- Commercial Support – CareDx