Belatacept-Based Regimens Versus a Cyclosporine A-Based Regimen in Kidney Transplant Recipients: 2-Year Results From the BENEFIT and BENEFIT-EXT Studies

Background. At 1 year, belatacept was associated with similar patient/graft survival, better renal function, and an improved cardiovascular/metabolic risk profile versus cyclosporine A (CsA) in the Belatacept Evaluation of Nephroprotection and Efficacy as Firstline Immunosuppression Trial (BENEFIT) and Belatacept Evaluation of Nephroprotection and Efficacy as Firstline Immunosuppression Trial-EXTended criteria donors (BENEFIT-EXT) studies. Acute rejection was more frequent with belatacept in BENEFIT. Posttransplant lymphoproliferative disorder (PTLD)-specifically central nervous system PTLD-was observed more frequently in belatacept-treated patients. This analysis assesses outcomes from BENEFIT and BENEFIT-EXT after 2 years of treatment.Methods. Patients received a more intensive (MI) or a less intensive (LI) regimen of belatacept or a CsA-based regimen.Results. Four hundred ninety-three of 666 patients(74%) in BENEFIT and 347 of 543(64%) in BENEFIT-EXT completed 2 years of treatment. the proportion of patients who survived with a functioning graft was similar across groups (BENEFIT: 94% MI, 95% LI, and 91% CsA; BENEFIT-EXT: 83% MI, 84% LI, and 83% CsA). Belatacept's renal benefits were sustained, as evidenced by a 16 to 17 mL/min (BENEFIT) and an 8 to 10 mL/min (BENEFIT-EXT) higher calculated glomerular filtration rate in the belatacept groups versus CsA. There were few new acute rejection episodes in either study between years 1 and 2. Because PTLD risk was highest in Epstein-Barr virus(EBV)(-) patients, an efficacy analysis of EBV(+) patients was performed and was consistent with the overall population results. There were two previously reported cases of PTLD in each study between years 1 and 2 in the belatacept groups. the overall balance of safety and efficacy favored the LI over the MI regimen.Conclusions. At 2 years, belatacept-based regimens sustained better renal function, similar patient/graft survival, and an improved cardiovascular/metabolic risk profile versus CsA; outcomes that were maintained in EBV (+) patients. No new safety signals emerged.Bristol-Myers SquibbGenentechPfizerNovartisAstellas PharmaGenzymeRocheEmory Univ, Sch Med, Emory Transplant Ctr, Atlanta, GA 30322 USAEmory Univ, Dept Surg, Atlanta, GA 30322 USAUniv Hosp Bellvitge, Div Nephrol, Barcelona, SpainHosp Rim & Hipertensao Unifesp, Dept Med, Div Nephrol, São Paulo, BrazilUniv Hosp Leuven, Dept Nephrol, Louvain, BelgiumUniv Calif San Francisco, Dept Med, Div Nephrol, Kidney Transplant Serv, San Francisco, CA USAMed Coll Wisconsin, Div Nephrol, Milwaukee, WI 53226 USAUniv Barcelona, Hosp Clin & Prov, Renal Transplantat Unit, Dept Nephrol, Barcelona, SpainMt Sinai Med Ctr, Recanati Miller Transplantat Inst, New York, NY 10029 USAInst Nefrol, Kidney Transplant Unit, Buenos Aires, DF, ArgentinaCHU Rangueil, Dept Nephrol Dialysis & Organ Transplantat, INSERM, U858,IFR 31, F-31054 Toulouse, FranceBristol Myers Squibb Co, Princeton, NJ USAUniv Paris S 11, Dept Nephrol, Bicetre Hosp, IFRNT, Villejuif, FranceHosp Rim & Hipertensao Unifesp, Dept Med, Div Nephrol, São Paulo, BrazilWeb of Scienc