Three-year outcomes in patients with delayed graft function in phase iii studies of belatacept vs cyclosporine in kidney transplantation (benefit and benefit-ext)

Introduction: Delayed graft function (DGF) results in diminished renal function post-transplant. Belatacept was associated with superior renal function and comparable patient and graft survival vs. CsA over 3 years in BENEFIT and BENEFIT-EXT, despite higher rate (BENEFIT only) and grades of acute rejection (AR).This report describes outcomes in patients with DGF in both studies. Methods: BENEFIT evaluated patients receiving living or standardcriteria deceased donor kidneys (SCD); BENEFIT-EXT studied patients receiving extended criteria donor kidneys (ECD). Each study compared belatacept more intensive (MI) or less intensive (LI) regimen vs CsA. This post-hoc analysis evaluated the 3-year outcomes of patients who experienced DGF (defined as dialysis in first week post transplantation). Patients randomized to CsA (but not belatacept) were eligible to receive a polyclonal antilymphocyte preparation for impaired renal function and anticipated DGF per protocol. Results: In BENEFIT and BENEFIT-EXT, 107/666 (16%; n=36 MI, n=31 LI, n=40 CsA) patients and 259/543 (48%; n=86 MI, n=83 LI, n=90 CsA) patients had DGF, respectively. Patient/graft survival and AR in the ITT population and DGF subgroups from both studies are shown in the Table. Among CsA patients, 6/40 (15%) in BENEFIT and 22/90 (24%) in BENEFIT-EXT received antilymphocyte therapy for anticipated DGF. In both trials, the differences in mean GFR favoring belatacept LI over CsA in the overall ITT populations were maintained in the DGF subgroups; approximately 20 mL/min/1.73m2 in BENEFIT and 10 mL/min/1.73m2 in BENEFIT-EXT. The incidence of SAEs was generally higher in the DGF cohort, primarily due to infections. Conclusions: The overall efficacy outcomes with belatacept LI were consistent with the ITT population. The differences in renal function with belatacept LI vs CsA in the ITT population were maintained in the DGF subgroups of both BENEFIT and BENEFIT-EXT. The incidence of SAEs was generally higher in the DGF cohort. The protocol-specified eligibility of CsA patients to receive antilymphocyte therapy for DGF represents a potential confounder in this analysis and results should be interpreted with caution. (Table Presented).