Phase III Study of Belatacept Versus Cyclosporine in Kidney Transplants from Extended Criteria Donors (BENEFIT‐EXT Study)

TLDR

Recipients of extended‑criteria donor kidneys face higher risk of graft dysfunction and may benefit from immunosuppression that avoids calcineurin‑inhibitor nephrotoxicity, and belatacept, a selective costimulation blocker, has been proposed to preserve renal function and improve long‑term outcomes. The study aimed to evaluate whether belatacept, given in more or less intensive regimens, could provide comparable patient/graft survival while improving renal function and reducing CNI nephrotoxicity in adult recipients of extended‑criteria donor kidneys. The 3‑year, Phase III BENEFIT‑EXT trial compared a more intensive (MI) and a less intensive (LI) belatacept regimen with cyclosporine in adult ECD kidney transplant recipients, using composite patient/graft survival and a composite renal impairment endpoint at 12 months as co‑primary outcomes. At 12 months, belatacept produced patient/graft survival comparable to cyclosporine, lower rates of composite renal impairment, higher mean GFR, a better cardiovascular/metabolic profile, but a higher incidence of post‑transplant lymphoproliferative disorder.

Abstract

Recipients of extended criteria donor (ECD) kidneys are at increased risk for graft dysfunction/loss, and may benefit from immunosuppression that avoids calcineurin inhibitor (CNI) nephrotoxicity. Belatacept, a selective costimulation blocker, may preserve renal function and improve long-term outcomes versus CNIs. BENEFIT-EXT (Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial-EXTended criteria donors) is a 3-year, Phase III study that assessed a more (MI) or less intensive (LI) regimen of belatacept versus cyclosporine in adult ECD kidney transplant recipients. The co-primary endpoints at 12 months were composite patient/graft survival and a composite renal impairment endpoint. Patient/graft survival with belatacept was similar to cyclosporine (86% MI, 89% LI, 85% cyclosporine) at 12 months. Fewer belatacept patients reached the composite renal impairment endpoint versus cyclosporine (71% MI, 77% LI, 85% cyclosporine; p = 0.002 MI vs. cyclosporine; p = 0.06 LI vs. cyclosporine). The mean measured glomerular filtration rate was 4-7 mL/min higher on belatacept versus cyclosporine (p = 0.008 MI vs. cyclosporine; p = 0.1039 LI vs. cyclosporine), and the overall cardiovascular/metabolic profile was better on belatacept versus cyclosporine. The incidence of acute rejection was similar across groups (18% MI; 18% LI; 14% cyclosporine). Overall rates of infection and malignancy were similar between groups; however, more cases of posttransplant lymphoproliferative disorder (PTLD) occurred in the CNS on belatacept. ECD kidney transplant recipients treated with belatacept-based immunosuppression achieved similar patient/graft survival, better renal function, had an increased incidence of PTLD, and exhibited improvement in the cardiovascular/metabolic risk profile versus cyclosporine-treated patients.