Posttransplant reduction in preexisting donor‐specific antibody levels after belatacept‐ versus cyclosporine‐based immunosuppression: Post hoc analyses of BENEFIT and BENEFIT‐EXT

摘要

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 style="fixed-case">BENEFIT, preexisting style="fixed-case">DSAs were detected in 4.6%, 4.9%, and 6.3% of belatacept style="fixed-case">MI‐treated, belatacept style="fixed-case">LI‐treated, and cyclosporine‐treated patients, respectively. The corresponding values in style="fixed-case">BENEFIT‐ style="fixed-case">EXT were 6.0%, 5.7%, and 9.2%. In both studies, most preexisting style="fixed-case">DSAs were of class I specificity. Over the first 24 months posttransplant, a greater proportion of preexisting style="fixed-case">DSAs in belatacept‐treated versus cyclosporine‐treated patients exhibited decreases or no change in style="fixed-case">MFI. style="fixed-case">MFI decline was more apparent with belatacept style="fixed-case">MI‐based versus belatacept style="fixed-case">LI‐based immunosuppression in both studies and more pronounced in style="fixed-case">BENEFIT‐ style="fixed-case">EXT versus style="fixed-case">BENEFIT. Although derived post hoc, these data suggest that belatacept‐based immunosuppression decreases preexisting style="fixed-case">DSAs more effectively than cyclosporine‐based immunosuppression.