Background: Published results of the completed 3-yr BENEFIT study reported comparable patient and graft survival and better renal function in kidney transplant recipients receiving belatacept vs a cyclosporine-based regimen, despite higher rates/grades of acute rejection. Patients who completed this trial and remained on assigned therapy were able to enter a long term extension (LTE). This report presents the results of the LTE study at 4 years. Methods: BENEFIT was a randomized, phase III study in adults receiving a kidney transplant from a living or standard criteria deceased donor. Patients were randomized to a more (MI) or less intensive (LI) regimen of belatacept, or CsA. Primary objective was to assess long-term safety of belatacept in the LTE cohort. Other endpoints included patient/graft survival, acute rejection, and calculated GFR (cGFR). Results: 457/471 patients who completed 3 years of treatment entered the LTE (n = 155/158 MI; n = 166/170 LI; n = 136/143 CsA). 25 patients discontinued the LTE between years 3 and 4 (n = 6 MI; n = 6 LI; n = 13 CsA). 4 patients died during year 4 (n = 1 MI; n = 3 CsA) and 1 experienced graft loss (n = 1 CsA). 2 patients experienced an acute rejection episode (n = 1 LI [Grade IIA]; n = 1 CsA [Grade IA]). For the population who entered the LTE, the incidence rate (events/100 pt-yrs of exposure) of serious infections from initial randomization through database lock was 10.3 (MI), 10.4 (LI), and 15.7 (CsA), and the incidence rate of overall malignancies was 2.3 (MI), 1.4 (LI), and 3.0 (CsA). No new cases of PTLD were observed, and no new safety signals were identified. cGFR (mean ±SD) at year 4 was 73.8 ± 19.6 (MI), 75.1± 17.0 (LI), and 50.0 ± 18.7 (CsA) mL/min/1.73 m2 (Figure).[Figure.]Conclusions: A consistent safety profile over time and a low discontinuation rate were observed in patients receiving belatacept in the LTE. A higher cGFR in belatacept-treated vs CsA-treated patients, first observed in the early post-transplant period, was sustained at 4 years.