Renal Function at 4 Years in a Phase 2 Randomized Trial Evaluating Belatacept-Based Regimens With Simultaneous Calcineurin Inhibitor and Corticosteroid Avoidance in Kidney Transplant Recipients.

Abstract

Background: Results of a 1-year, Phase 2 trial comparing 2 belatacept (bela) regimens with a tacrolimus (TAC)-based regimen (all steroid free) demonstrated improved renal function with bela (8-10 mL/min higher calculated[c] GFR) vs. TAC in the intent-to-treat cohorts (Ferguson R et al, AJT 2011;11(1):66-76). Here, we report on-treatment renal function through Month (M) 48 post-transplant, in order to assess the long-term renal function benefit of bela vs. TAC. Methods: This was an open-label, multicenter study in EBV+ patients(pts) who received rabbit anti-thymocyte globulin at 1.5 mg/kg for 4 days post-transplant and were randomized 1:1:1 to 1) bela+MMF, 2) bela+sirolimus (SRL), or 3) TAC+MMF. Pts received steroids for 4 days. Renal function was assessed by cGFR (MDRD Levey equation). Pts could enter the LTE after M12. Results: Out of 89 treated subjects, 73 (27 bela-MMF, 19 bela-SRL and 27 TAC-MMF) entered the LTE; 25, 16, and 20 pts remained on study therapy at M48. On-treatment analysis revealed that mean(SD) GFR at M1 post-transplant was higher in both bela groups vs. TAC: 55.1(16) bela+MMF, 61.7(29) bela+SRL, and 43.9(14.41) mL/min/1.73m2 TAC+MMF, and mean cGFR remained higher with bela vs. TAC through M48: 59.6(15) bela+MMF, 72.2(25) bela+SRL, and 55.7(14) mL/min/1.73m2 TAC+MMF (Figure). At M12, mean(SD) trough levels for SRL and TAC were 9.0(4) and 9.6(3), respectively. Conclusion: These data demonstrate numerically higher cGFR with bela+SRL through M48 in the LTE cohort vs. TAC but should be interpreted with caution due to small sample sizes and potential bias of on-treatment analyses.Figure: No Caption available.DISCLOSURE:Woodle, E.: Grant/Research Support, Bristol-Myers Squibb. Harler, M.: Employee, Bristol-Myers Squibb. Vincenti, F.: Grant/Research Support, Bristol-Myers Squibb, Alexion, Pfizer, Astellas, Novartis, Genentech.