Abstract: SA-PO001
Outcomes of Belatacept Regimen with the Use of Precision Medicine in Kidney Transplantation
Session Information
- Transplantation: Clinical Outcomes
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 1802 Transplantation: Clinical
Authors
- Shoji, Jun, University of California San Francisco, San Francisco, California, United States
- Tang, Qizhi, University of California San Francisco School of Medicine, San Francisco, California, United States
- Vincenti, Flavio, University of California San Francisco, San Francisco, California, United States
Background
Belatacept is a costimulation blocker that has been increasingly used as maintenance immunosuppression to improve long term outcomes in kidney transplant recipients. Since acute rejection in patients on belatacept have been noted to be more frequent and histologically more severe, identifying the select population of patients with Precision Medicine who will benefit from belatacept is important. We investigated pretransplant recipient immune profiles to determine which lymphocyte populations would be the best predictor in identifying patients who will be at lowest risk for costimulation blockade-resistant rejection.
Methods
We prospectively enrolled 64 kidney transplant recipients (44 deceased; 20 living donors) at our center to receive denovo belatacept from August 2012 to March 2017. PMBCs were collected prior to transplantation and at the time of cause and protocol biopsies. All patients received thymoglobulin for induction with belatacept 10mg/kg administered on POD 1, 4, 14, 28, 56, and 84. Monthly maintenance dose of 5mg/kg was given starting week 16. Patients were initially on MMF but were converted to everolimus after 1 month. Prednisone was maintained on 56 patients and withdrawn on 8 patients. Protocol biopsies were performed at 6 months.
Results
On cause biopsies, 3 patients were noted to have ACR 1a (at 4 weeks, 6 weeks, 4 months), 1 with ACR 1b (at 2 months), 3 with ACR 2b (at 2 months, 3 months, 9 months), 1 with AMR (at 4 months), and 1 with simultaneous ACR 1a and AMR (at 7 months). In addition, 16 patients were found to have borderline rejection on protocol biopsies. 28 patients did not have any inflammation on biopsies. 56 patients remained on belatacept and 8 patients were converted to tacrolimus (1 patient was switched to tacrolimus due to poor intravenous access and not due to rejection). 6 of the 9 rejections occurred in those who were on MMF and not on mTORi. 2 of 9 patients who were noted to have rejection were patients on steroid withdraw.
Conclusion
CD28-CD8 T cells are associated with belatacept-resistant rejection since these are memory cells unaffected by CD28 blockade. Pretransplant immunotyping and functional assessment of circulating lymphocytes may provide a useful tool for selection of patients suitable for belatacept therapy.