Novel Strategy to Improve the Efficacy of Belatacept.

Abstract

Introduction Belatacept used with basiliximab and MMF/corticosteroids has been associated with a higher eGFR compared to cyclosporine. However, acute rejection was higher with belatacept at 17% vs. 7% with cyclosporine. Non-human primate studies have shown synergism with the combined use of belatacept and mTOR inhibitors. We investigated the safety and efficacy of a novel immunosuppression regimen utilizing belatacept with rATG induction (3 mg/Kg) and initial MMF maintenance with conversion to everolimus at 1 month post-transplant ± corticosteroids. Methods Retrospective analysis of the first 19 renal transplant recipients who received our de novo belatacept regimen (Group 1) compared to a historical control group of 38 patients who met the de novo belatacept inclusion/exclusion criteria (EBV seropositive and low immunologic risk) but were placed on a regimen of basiliximab induction with tacrolimus/MMF maintenance ± corticosteroids (Group 2). Groups were matched for the following variables: type of kidney transplant, ESRD cause, CIT, and steroid withdrawal. We compared eGFR and rates of acute rejection and infection at 6 months post-transplant. Results Baseline characteristics were similar between the groups with the exception of the development of DGF which occurred in 7 and 3 patients in Groups 1 and 2, respectively (P=0.01). Mean cPRA (SD) was 6.2 (13.7) and 2.9 (8) for Groups 1 and 2, respectively (P=0.26). In Groups 1 and 2 there were 15 and 29 patients who remained on a corticosteroid maintenance regimen, respectively (P=1.0). Mean tacrolimus trough levels (SD) for Group 2 at months 1, 3, and 6 were 9.8 (2.8), 8.4 (2.3), and 8.6 (3.1), respectively. Mean everolimus trough levels (SD) for Group 1 at month 3 and 6 were 5.3 (2.9) and 5.8 (2.7), respectively. Acute rejection occurred in 1 (type 2b) and 3 (2 type 1a and 1 type 1b) patients in Groups 1 and 2, respectively (P=1.0). Renal function was similar between the Groups at months 1, 3, and 6.Table: No Caption available.Similar rates of infections (CMV viremia, BK viremia, and UTI) were seen in both groups. Conclusion Our de novo belatacept protocol is a novel immunosuppression strategy that yielded a lower than previously reported acute rejection rate at 5.3% while maintaining a similar safety profile compared to a tacrolimus based regimen in the short term. Longer term follow-up will be needed to better assess the safety and efficacy of this strategy as well as to evaluate the impact on renal allograft function. DISCLOSURES:Wojciechowski, D.: Grant/Research Support, BMS, Novartis. Chandran, S.: Grant/Research Support, BMS. Vincenti, F.: Grant/Research Support, BMS, Novartis.