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

R A Bray, H M Gebel, R Townsend, M E Roberts, M Polinsky, L Yang, H-U Meier-Kriesche, C P Larsen, R A Bray, H M Gebel, R Townsend, M E Roberts, M Polinsky, L Yang, H-U Meier-Kriesche, C P Larsen

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.

Keywords: antibody biology; clinical research/practice; clinical trial; immunosuppressant - calcineurin inhibitor: cyclosporine A (CsA); immunosuppressant - fusion proteins and monoclonal antibodies: belatacept; kidney transplantation/nephrology.

© 2018 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.

Figures

Figure 1
Figure 1
MFI between baseline and month 24 in the subsets of patients in BENEFIT and BENEFIT‐EXT with preexisting DSAs. Dashed lines denote MHC class II preexisting DSAs. CsA, cyclosporine; DSA, donor‐specific antibody; LI, less intense; MFI, mean fluorescence intensity; MHC, major histocompatibility complex; MI, more intense
Figure 2
Figure 2
Kaplan–Meier curve for time to death or graft loss in patients with or without DSAs in (A) BENEFIT and (B) BENEFIT‐EXT. DSA, donor‐specific antibody; LI, less intense; MI, more intense
Figure 3
Figure 3
Mean estimated GFR (observed) in the subsets of patients with preexisting DSAs in (A) BENEFIT and (B) BENEFIT‐EXT. CI, confidence interval; DSA, donor‐specific antibodies; eGFR, estimated GFR; LI, less intense; MI, more intense

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Source: PubMed

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