Posttransplant reduction in preexisting donor‐specific antibody levels after belatacept‐ versus cyclosporine‐based immunosuppression: Post hoc analyses of BENEFIT and BENEFIT‐EXT. Issue 7 (17th April 2018)

• Record Type: Journal Article
• Authors: Bray, R. A.; Gebel, H. M.; Townsend, R.; Roberts, M. E.; Polinsky, M.; Yang, L.; Meier‐Kriesche, H.‐U.; Larsen, C. P.
• Is Part Of: American journal of transplantation. Volume 18:Issue 7(2018)
• Page Start: 1774
• Page End: 1782
• Publication Date: 2018-04-17
• Subjects: antibody biology -- clinical research/practice -- clinical trial -- immunosuppressant ‐ calcineurin inhibitor: cyclosporine A (CsA) -- immunosuppressant ‐ fusion proteins and monoclonal antibodies: belatacept -- kidney transplantation/nephrology; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.14738
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : BENEFIT and BENEFIT‐EXT were phase III studies of cytotoxic T‐cell crossmatch–negative kidney transplant recipients randomized to belatacept more intense (MI)‐based, belatacept less intense (LI)‐based, or cyclosporine‐based immunosuppression. Following study completion, presence/absence of HLA‐specific antibodies was determined centrally via solid‐phase flow cytometry screening. Stored sera from anti‐HLA–positive patients were further tested with a single‐antigen bead assay to determine antibody specificities, presence/absence of donor‐specific antibodies (DSAs), and mean fluorescent intensity (MFI) of any DSAs present. The effect of belatacept‐based and cyclosporine‐based immunosuppression on MFI was explored post hoc in patients with preexisting DSAs enrolled to BENEFIT and BENEFIT‐EXT. In BENEFIT, preexisting DSAs were detected in 4.6%, 4.9%, and 6.3% of belatacept MI‐treated, belatacept LI‐treated, and cyclosporine‐treated patients, respectively. The corresponding values in BENEFIT‐EXT were 6.0%, 5.7%, and 9.2%. In both studies, most preexisting DSAs were of class I specificity. Over the first 24 months posttransplant, a greater proportion of preexisting DSAs in belatacept‐treated versus cyclosporine‐treated patients exhibited decreases or no change in MFI. MFI decline was more apparent with belatacept MI‐based versus belatacept LI‐based immunosuppression in both studies and more pronounced in BENEFIT‐EXT versus BENEFIT. Although derived post hoc, these data suggest that belatacept‐based immunosuppression decreases preexisting DSAs more effectively than cyclosporine‐based immunosuppression. Abstract : Post hoc analysis indicates that belatacept‐based immunosuppression decreases preexisting, donor‐specific HLA antibody more effectively than cyclosporine‐based immunosuppression.