NEW IMMUNOSUPPRESSIVE AGENTS

A. Durrbach¹, C. Larsen², J.O.M. Pestana³, H. De jonge⁴, F. Vincenti⁵, S. Florman⁶, J. Xing⁷, A. Block⁸, P. Garg⁸, J.M. Grinyó^9
1Nephrology Unit, Bicetre Hospital, Le Kremlin-Bicêtre/FRANCE, ²Emory Transplant Center, Emory University School of Medicine, Atlanta/GA/UNITED STATES OF AMERICA, ³Nephrology, Hospital do Rim e Hipertensão, Sâo Paulo/BRAZIL, ⁴Nephrology Department, University Hospital Leuven, Leuven/BELGIUM, ⁵, UCSF, San Francisco/UNITED STATES OF AMERICA, ⁶, Mount Sinai Medical Center, New York/NY/UNITED STATES OF AMERICA, ⁷, Bristol-Myers Squibb, Hopewell/NJ/UNITED STATES OF AMERICA, ⁸, Bristol-Myers Squibb, Princeton/NJ/UNITED STATES OF AMERICA, ⁹Nephrology, University of Barcelona, Hospital Universitari de Bellvitge, Barcelona/SPAIN

Body: Introduction: Belatacept-based regimens were associated with better renal function, with comparable patient/graft survival and acute rejection (AR) vs a cyclosporine (CsA)-based regimen in extended criteria donor (ECD) kidney transplant recipients at 1 year in the BENEFIT-EXT study. The current analysis assesses pre-specified outcomes from BENEFIT-EXT in the intent-to-treat population after 2 years of treatment.
Methods: BENEFIT-EXT is a 3-year, randomized, Phase III study in adults receiving an ECD kidney transplant. Patients were randomized 1:1:1 to a more intensive (MI) or less intensive (LI) regimen of belatacept or CsA; all patients received basiliximab induction, MMF, and corticosteroids.
Results: 543 patients were randomized and transplanted; 347 completed 2 years on treatment (n=116 MI, n=119 LI; n=112 CsA). Patient/graft survival was similar across groups (83% MI, 84% LI, 83% CsA) at 2 years. The renal benefit of belatacept was sustained at Year 2 as assessed by the measured GFR (52 mL/min MI, 50 mL/min LI, and 45 mL/min CsA; p=0.028 MI vs CsA; p=0.108 LI vs CsA) and by the calculated GFR (8-10 mL/min higher in the belatacept groups vs CsA). There were 3 additional episodes of acute rejection after the first year (n=1 LI; n=2 CsA). The cardiovascular and metabolic risk profile benefits of belatacept vs CsA on serum lipids and blood pressure were sustained. The overall incidence rates of malignancies and serious infections remained comparable across groups. There were 2 previously reported cases of PTLD between Years 1 and 2 (n=1 each MI and LI; total cases through July 2009 in BENEFIT-EXT: n = 2 MI; n = 3 LI; n = 0 CsA). The overall safety profile remained similar across groups.
Conclusions: A belatacept-based regimen maintained better renal function, a better cardiovascular/metabolic risk profile, and similar patient/graft survival vs CsA at 2 years. There appeared to be no additional efficacy gained by using the MI regimen vs the LI regimen. No new safety signals emerged. Belatacept is a promising option in patients receiving ECD kidneys.

Disclosure: All authors have declared no conflicts of interest.