De novo donor-specific antibodies in belatacept-treated vs cyclosporine-treated kidney-transplant recipients: Post hoc analyses of the randomized phase III BENEFIT and BENEFIT-EXT studies

• 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 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1111/ajt.14721
• Title of Journal or Parent Work: American Journal of Transplantation
• ISSN: 1600-6135
• Volume: 18
• Issue: 7
• Start Page: 1783
• End Page: 1789
• Grant/Funding Information: 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.; The BENEFIT and BENEFIT‐EXT studies were sponsored by Bristol‐Myers Squibb
• Keywords: cyclosporin A (CsA); Surgery; immunosuppressant - calcineurin inhibitor; OUTCOMES; practice; Transplantation; clinical trial; Science & Technology; immunosuppressant - fusion proteins and monoclonal antibodies; belatacept; clinical research; antibody biology; nephrology; Life Sciences & Biomedicine; kidney transplantation; EXPOSURE
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Donor-specific antibodies (DSAs) are associated with an increased risk of antibody-mediated rejection and graft failure. In BENEFIT and BENEFIT-EXT, kidney-transplant recipients were randomized to receive belatacept more intense (MI)–based, belatacept less intense (LI)–based, or cyclosporine-based immunosuppression for up to 7 years (84 months). The presence/absence of HLA-specific antibodies was determined at baseline, at months 6, 12, 24, 36, 48, 60, and 84, and at the time of clinically suspected episodes of acute rejection, using solid-phase flow-cytometry screening. Samples from anti-HLA-positive patients were further tested with a single-antigen bead assay to determine antibody specificities, presence/absence of DSAs, and mean fluorescence intensity (MFI) of any DSAs present. In BENEFIT, de novo DSAs developed in 1.4%, 3.5%, and 12.1% of belatacept MI-treated, belatacept LI-treated, and cyclosporine-treated patients, respectively. The corresponding values in BENEFIT-EXT were 3.8%, 1.1%, and 11.2%. Per Kaplan-Meier analysis, de novo DSA incidence was significantly lower in belatacept-treated vs cyclosporine-treated patients over 7 years in both studies (P <.01). In patients who developed de novo DSAs, belatacept-based immunosuppression was associated with numerically lower MFI vs cyclosporine-based immunosuppression. Although derived post hoc, these data suggest that belatacept-based immunosuppression suppresses de novo DSA development more effectively than cyclosporine-based immunosuppression.