Long-Term Extension of the Belatacept BENEFIT-EXT Study: Results at Month 48

Abstract

Background: Published results from the completed BENEFIT-EXT study reported comparable patient and graft survival and better renal function in belatacept-treated patients versus a cyclosporine-based regimen. Patients who completed this trial and remained on assigned therapy were eligible to enter a long term extension (LTE). This report presents the results of the LTE study at 4 years. Methods: BENEFIT-EXT was a 3-year, phase III study in recipients of de novo extended criteria donor kidneys who were randomized to a more intensive (MI) or less intensive (LI) belatacept regimen, or cyclosporine (CsA). Primary objective was to assess long-term safety and tolerability of belatacept in the LTE cohort. Other endpoints included patient/graft survival, acute rejection, and calculated GFR (cGFR). Results: 304/323 patients who completed 3 years of treatment entered the LTE (n = 104 MI; n = 113 LI; n = 87 CsA). 16 patients discontinued the LTE between years 3 and 4 (n = 7 MI; n = 6 LI; n = 3 CsA). 6 patients died during year 4 (n = 2 MI; n = 4 LI) and 2 experienced graft loss (n = 1 LI; n = 1 CsA). One belatacept MI patient experienced an acute rejection episode (Grade IIA) during year 4. For the population who entered the LTE, the incidence rate (events/100 pt-yrs of exposure) of serious infections from randomization through database lock was 23.8 (MI), 15.9 (LI), and 18.7 (CsA), and the incidence rate of overall malignancies was 2.6 (MI), 3.2 (LI), and 2.8 (CsA). 4 cases of post-transplant lymphoproliferative disorder (PTLD) occurred in the LTE population through August 2011 (n = 3 LI; n = 1 CsA). 2 of 3 PTLD cases in the LI group occurred in patients seronegative for Epstein-Barr virus (EBV) at the time of transplantation. cGFR (mean ± SD) at year 4 was 54.5 ± 18.0 (MI), 53.5 ± 19.1 (LI), and 42.4 ± 16.5 (CsA) mL/min/1.73 m2 (Figure).[Figure]Conclusions: The safety profile of belatacept was consistent over time; no new safety concerns were identified. Two of three new cases of PTLD occurred in EBV negative patients; use of belatacept has since been contraindicated in patients who are EBV negative or have unknown serostatus. A higher cGFR in belatacept-treated vs CsA-treated patients was maintained over time.