NEW IMMUNOSUPPRESSIVE AGENTS

C. Larsen¹, J.M. Grinyó², B. Charpentier³, J.O.M. Pestana⁴, N. Kamar⁵, H. De jonge⁶, C. Lin⁷, G. Di russo⁸, P. Garg⁸, F. Vincenti^9
1Emory Transplant Center, Emory University School of Medicine, Atlanta/GA/UNITED STATES OF AMERICA, ²Nephrology, University of Barcelona, Hospital Universitari de Bellvitge, Barcelona/SPAIN, ³Nephrology And Transplantation Dept, Bicetre Hospital, Paris/FRANCE, ⁴Nephrology, Hospital do Rim e Hipertensão, Sâo Paulo/BRAZIL, ⁵Department Of Nephrology, Dialysis And Organ Transplantation, University Hospital, Toulouse/FRANCE, ⁶Nephrology Department, University Hospital Leuven, Leuven/BELGIUM, ⁷, Bristol-Myers Squibb, Hopewell/NJ/UNITED STATES OF AMERICA, ⁸, Bristol-Myers Squibb, Princeton/NJ/UNITED STATES OF AMERICA, ⁹, UCSF, San Francisco/UNITED STATES OF AMERICA

Body: Introduction: Belatacept-based regimens were associated with superior renal function and similar patient/graft survival vs cyclosporine (CsA) at 1 year in the BENEFIT study, despite an increase in acute rejection (AR) in the early post-transplant period. The current analysis assesses pre-specified outcomes from BENEFIT in the intent-to-treat population after 2 years of treatment.
Methods: BENEFIT is a 3-year, randomized, phase III study in adults receiving a kidney transplant from a living or standard criteria deceased donor. 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: 666 patients were randomized and transplanted; 493 (n = 164 MI; n = 176 LI; n= 153 CsA) completed 2 years on treatment. Patient/graft survival was similar across groups (94% MI; 95% LI; 91% CsA) at Year 2. The superior renal benefit of belatacept-based regimens was sustained through Year 2, as evidenced by a 15 – 17 mL/min higher measured GFR (p < 0.0001 MI or LI vs CsA) or calculated GFR in the belatacept groups vs CsA. There were 8 additional patients with an AR episode between Year 1 and Year 2 (n = 4 MI; n = 4 CsA). The improvements in the cardiovascular and metabolic risk profile for belatacept vs CsA were sustained, and an additional beneficial effect on LDL-cholesterol emerged at Year 2 (p ≤ 0.002 MI or LI vs CsA). The overall incidence rate of malignancies and serious infections remained comparable across groups. There were 2 previously reported cases of PTLD between Year 1 and Year 2 in the MI group (total cases in BENEFIT through July 2009: n = 3 MI; n = 2 LI; n = 1 CsA). The overall safety profile remained similar across groups.
Conclusions: At 2 years, a belatacept-based regimen demonstrated sustained superior renal function and similar patient/graft survival vs CsA. There was no additional efficacy gained by using the MI regimen vs the LI regimen. No new safety signals emerged. Belatacept is a promising therapeutic option in kidney transplant patients.

Disclosure: All authors have declared no conflicts of interest.