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

Am J Transplant. 2018 Jul;18(7):1783-1789. doi: 10.1111/ajt.14721. Epub 2018 Apr 2.


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.

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

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept / therapeutic use*
  • Adult
  • Cyclosporine / therapeutic use*
  • Female
  • Follow-Up Studies
  • Graft Rejection / blood
  • Graft Rejection / drug therapy*
  • Graft Rejection / etiology
  • Graft Survival / immunology
  • Humans
  • Immune Tolerance / immunology
  • Immunosuppressive Agents / therapeutic use
  • International Agencies
  • Isoantibodies / blood*
  • Isoantibodies / immunology
  • Kidney Failure, Chronic / surgery*
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Postoperative Complications
  • Prognosis
  • Risk Factors
  • Tissue Donors*
  • Transplant Recipients


  • Immunosuppressive Agents
  • Isoantibodies
  • Abatacept
  • Cyclosporine