title: A phase III study of belatacept versus cyclosporine in kidney transplants from extended criteria donors (BENEFIT-EXT study).
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.
authors.affiliation: Bicêtre Hospital, Kremlin Bicêtre, IFRNT, Université Paris sud, France. antoine.durrbach@bct.aphp.fr
authors.forename: A
authors.initials: A
authors.lastname: Durrbach
authors.forename: J M
authors.initials: JM
authors.lastname: Pestana
authors.forename: T
authors.initials: T
authors.lastname: Pearson
authors.forename: F
authors.initials: F
authors.lastname: Vincenti
authors.forename: V D
authors.initials: VD
authors.lastname: Garcia
authors.forename: J
authors.initials: J
authors.lastname: Campistol
authors.forename: M del Carmen
authors.initials: Mdel C
authors.lastname: Rial
authors.forename: S
authors.initials: S
authors.lastname: Florman
authors.forename: A
authors.initials: A
authors.lastname: Block
authors.forename: G
authors.initials: G
authors.lastname: Di Russo
authors.forename: J
authors.initials: J
authors.lastname: Xing
authors.forename: P
authors.initials: P
authors.lastname: Garg
authors.forename: J
authors.initials: J
authors.lastname: Grinyó
mesh_terms: D000069594:Abatacept; D000328:Adult; D065095:Calcineurin Inhibitors; D002318:Cardiovascular Diseases / Q000209:etiology; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012306:Risk
chemical_list: D065095:Calcineurin Inhibitors; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept; D016572:Cyclosporine