Validation of the iBox Surrogate End Point in CNI Free, Belatacept Treated Patients (BENEFIT & BENEFIT-EXT)

G. Divard¹, O. Aubert¹, M. Raynaud¹, F. Vincenti², L. Rostaing³, A. Durbach⁴, C. Legendre¹, R. Vadanici⁵, A. Loupy¹, -. BENEFIT & BENEFIT-EXT Investigators⁶

¹Paris Transplant Group, INSERM, Paris, France, ²UCSF, San Francisco, CA, ³Grenoble, Grenoble, France, ⁴APHP, Paris, France, ⁵BMS, Rueil Malmaison, France, ⁶BMS, New York, NY

Meeting: 2022 American Transplant Congress

Abstract number: 412

Keywords: Co-stimulation, Graft survival, Immunosuppression, Kidney transplantation

Topic: Clinical Science » Kidney » 38 - Kidney Immunosuppression: Novel Regimens and Drug Minimization

Session Information

Session Name: Kidney Immunosuppression

Session Type: Rapid Fire Oral Abstract

Date: Tuesday, June 7, 2022

Session Time: 3:30pm-5:00pm

Presentation Time: 4:00pm-4:10pm

Location: Hynes Room 302

*Purpose: The iBox is a prognostication system for long-term kidney allograft survival, developed with mostly patients under a CNI based immunosuppression. Patients treated with a belatacept regimen increased their eGFR without significantly improve their long-term graft survival in the two large BENEFIT & BENEFIT-EXT randomized control trials (RCTs). This study aims to evaluate the performances of the iBox system to capture this hemodynamic effect to predict long term graft survival in patients under a CNI free regimen in two large RCTs.

*Methods: The two large RCTs BENEFIT (NCT00256750) and BENEFIT-EXT (NCT00114777) studies comparing kidney transplant recipient receiving two belatacept regimens to a standard CNI regimen were included. We used a data curation to use the validated data from the per-protocol population, and the apply the iBox integrative and validated risk score (NCT03474003), which use the biological, immunological and histological parameters measured at one-year post-randomization. The predictive performances of the iBox have been compared with the observed graft survival at 6-year post risk evaluation, to assess for the discrimination capability (C-index) and the calibration (graphical method).

*Results: A total of 917 patients reached the one-year visit (614 under belatacept, 303 under CNI) of whom 867 were included. After a median follow-up of 5.97 [3.76-5.99] years post-evaluation, only 31 (3.56%) graft losses occurred. At one year, the mean eGFR was 56.8 ± 18.1 ml/min/1.73m², dipstick proteinuria was positive for 154 (17.7%) patients, 42 (4.8%) patients had a positive DSA and 667 (76.9%) had a biopsy. The predictive performances of the iBox system shows a good discrimination with C-stat of 0.758 at 6-year post risk evaluation and an adequate calibration.

*Conclusions: This study confirms the good performances of the iBox system to predict long term allograft survival in patients under a CNI-free based immunosuppression. Given the unmet need for surrogate end point for clinical trials, this study shows the potential of the iBox system to fast track the development and approval of CNI-free immunosuppressive regimen strategies.

To cite this abstract in AMA style:

Divard G, Aubert O, Raynaud M, Vincenti F, Rostaing L, Durbach A, Legendre C, Vadanici R, Loupy A. Validation of the iBox Surrogate End Point in CNI Free, Belatacept Treated Patients (BENEFIT & BENEFIT-EXT) [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/validation-of-the-ibox-surrogate-end-point-in-cni-free-belatacept-treated-patients-benefit-benefit-ext/. Accessed May 30, 2025.

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