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

• Type of Material: Article
• Authors: Robert A Bray, Emory University; Howard Gebel, Emory University; R. Townsend, Bristol-Myers Squibb; M. E. Roberts, Bristol-Myers Squibb; M Polinsky, Bristol-Myers Squibb; L Yang, Bristol-Myers Squibb; H.-U. Meier-Kriesche, Bristol-Myers Squibb; Christian P Larsen, Emory University
• Language: English
• Date: 2018-07-01
• Publisher: Wiley: 12 months
• Publication Version: Final Published Version
• Copyright Statement: © 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
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1111/ajt.14738
• Title of Journal or Parent Work: American Journal of Transplantation
• ISSN: 1600-6135
• Volume: 18
• Issue: 7
• Start Page: 1774
• End Page: 1782
• Grant/Funding Information: The BENEFIT and BENEFIT‐EXT studies were sponsored by Bristol‐Myers Squibb.; Support for third‐party writing assistance for this manuscript was provided by Tiffany DeSimone, PhD, of CodonMedical, an Ashfield Company, part of UDG Healthcare plc, and was funded by Bristol‐Myers Squibb.
• Keywords: practice; RECIPIENTS; Transplantation; EXPOSURE; Surgery; kidney transplantation; immunosuppressant - calcineurin inhibitor: cyclosporine A (CsA); nephrology; antibody biology; Life Sciences & Biomedicine; clinical trial; KIDNEY-TRANSPLANTATION; HLA ANTIBODIES; immunosuppressant - fusion proteins and monoclonal antibodies: belatacept; OUTCOMES; clinical research; PHASE-III; Science & Technology
• Research Categories: Health Sciences, Pathology; Health Sciences, Medicine and Surgery

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.