Date: Monday, June 13, 2016
Session Time: 4:30pm-6:00pm
Presentation Time: 4:30pm-4:42pm
Location: Ballroom A
Kidney transplantation remains limited by toxicities of calcineurin inhibitors (CNIs) and steroids. Belatacept is a less toxic CNI alternative delivered by monthly intravenous infusion, but its clinical use has been hampered by early, high-grade acute rejections. We have reported that a regimen including a single intraoperative dose of alemtuzumab followed by monthly belatacept and daily sirolimus can prevent rejection of live (LD) or deceased (DD) donor kidney transplants, including allosensitized individuals and recipients of extended criteria donor (ECD) kidneys. Herein we report the follow-up on the initial 40 patient cohort. Graft and patient survival remains 100%. One patient withdrew from protocol due to pregnancy; 39 patients remain on protocol, all of who have enjoyed stable and excellent graft function. The trial enrolled in two cohorts of 20. Median follow-up in cohort 1 (all LD) is > 60 months with a mean creatinine of 1.20 mg/dl. Median follow-up in cohort 2 (LD, DD, ECD) is 24 months with a mean creatinine of 1.4 mg/dl. Three patients in each cohort have been intolerant to sirolimus, requiring conversion to mycophenolate. In cohort 1, 6 of 20 patients were weaned to monotherapy belatacept with follow-up on monotherapy exceeding 3 years, and in cohort 2, 4 patients have been weaned to monotherapy belatacept with a mean follow up on monotherapy of 6 months. Additional patients are approaching eligibility for sirolimus withdrawal. Mechanistic study of all patients indicate that post depletional repopulation under this regimen facilitates significant (p<0.01) enrichment for naïve CD28+ T cells, reduction of CD28- T memory cells, and augmentation of regulatory T and B cell phenotypes; all characteristics that favor belatacept-based immunosuppression. Recipients exhibit donor-specific hyporesponsiveness without impaired CMV or EBV-specific immunity. Continued follow-up of this pilot experience indicates that belatacept and sirolimus effectively prevent kidney allograft rejection without CNIs or steroids when used following alemtuzumab induction, and provides insight as to the etiology of early belatacept-resistant rejection. Prospective controlled trials of this regimen using broad inclusion criteria are warranted.
CITATION INFORMATION: Guasch A, Xu H, Mehta A, Ghali A, Mead S, Gebel H, Bray R, Larsen C, Pearson T, Kirk A. A Pathway to Belatacept Monotherapy: Alemtuzumab, Belatacept and Rapamycin for Kidney Transplantation. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Guasch A, Xu H, Mehta A, Ghali A, Mead S, Gebel H, Bray R, Larsen C, Pearson T, Kirk A. A Pathway to Belatacept Monotherapy: Alemtuzumab, Belatacept and Rapamycin for Kidney Transplantation. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/a-pathway-to-belatacept-monotherapy-alemtuzumab-belatacept-and-rapamycin-for-kidney-transplantation/. Accessed March 3, 2021.
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