NEW IMMUNOSUPPRESSIVE AGENTS

L. Rostaing¹, G. Nainan², M.C. Rial³, S. Steinberg⁴, F. Vincenti⁵, R. Shi⁶, G. Di russo⁷, D. Thomas⁷, J.M. Grinyó^8
1Dept Of Nephrology, Dialysis And Organ Transplantation, Toulouse University Hospital, Toulouse/FRANCE, ², Lakeshore Hospital, Cochin/INDIA, ³Transplantation, Instituto de Nefrología, Buenos Aires/ARGENTINA, ⁴, California Institute of Renal Research, San Diego/UNITED STATES OF AMERICA, ⁵, UCSF, San Francisco/CA/UNITED STATES OF AMERICA, ⁶, Bristol-Myers Squibb, Hopewell/NJ/UNITED STATES OF AMERICA, ⁷, Bristol-Myers Squibb, Princeton/NJ/UNITED STATES OF AMERICA, ⁸Nephrology, University of Barcelona, Hospital Universitari de Bellvitge, Barcelona/SPAIN

Body: Introduction: Prolonged use of calcineurin inhibitors (CNIs) in kidney transplant recipients is associated with progressive renal damage and extra-renal toxicities, including effects on cardiovascular risk factors. A switch to a belatacept-based regimen may be a safe option for patients maintained on tacrolimus or cyclosporine immunosuppression.
Methods: This is a 12-month, randomized, open-label Phase II study of kidney transplant patients with stable renal function (MDRD GFR ≥35 mL/min and ≤75 mL/min) on a CNI-based regimen (either tacrolimus or cyclosporine). Patients 6 to 36 months post-transplantation were randomized to either belatacept 5 mg/kg (with CNI discontinuation) or continued treatment with their established CNI. All patients also continued background maintenance immunosuppression at stable doses, which could include mycophenolate, sirolimus, or azathioprine +/- corticosteroids. The primary outcome was the change in MDRD GFR from baseline to Month 12 following switch. Additional outcomes included the incidence and severity of acute rejection (AR) episodes and patient/graft survival at Month 12.
Results: 173 patients were randomized, and 171 were either switched to belatacept (n = 83) or remained on a CNI-based regimen (n = 88). At Month 12, the mean increase from baseline in MDRD GFR was 7.0 mL/min ± 11.99 in the belatacept group and was 2.1 mL/min ± 10.34 in the CNI group. Six patients in the belatacept group (7%) had an AR episode, vs none in the CNI group. All AR episodes occurred within the first 6 months, were Banff grade I or II, and none led to graft loss. Patient/graft survival was 100% in the belatacept group and was 99% in the CNI group at Month 12. One patient in the CNI group died due to myocardial infarction with a functioning graft. The overall safety profile was similar between groups. Four patients (2 in each group) had malignancies during the first 12 months. No cases of PTLD were reported.
Conclusions: Switching to a belatacept-based regimen from a CNI-based regimen was safe, was associated with low rates of acute rejection, and resulted in improved renal function.

Disclosure: All authors have declared no conflicts of interest.