IMMUNOSUPPRESSION WITH BELATACEPT-BASED, CNI-AVOIDING AND STEROID-AVOIDING REGIMENS VS A TACROLIMUS-BASED, STEROID-AVOIDING REGIMEN IN KIDNEY TRANSPLANT PATIENTS: RESULTS OF A 1-YEAR, RANDOMIZED STUDY

NEW IMMUNOSUPPRESSIVE AGENTS

R. Ferguson¹, F. Vincenti², D. Kaufman³, E.S. Woodle⁴, B. Marder⁵, F. Citterio⁶, W.H. Marks⁷, Y. Dong⁸, M. Agarwal⁹, P. Garg⁹, J.M. Grinyó^10
1Division Of Transplantation, Department Of Surgery, The Ohio State University College of Medicine and Public Health, Columbus/OH/UNITED STATES OF AMERICA, ², UCSF, San Francisco/CA/UNITED STATES OF AMERICA, ³Dept Of Surgery, Feinberg School of Medicine, Northwestern University, Chicago/IL/UNITED STATES OF AMERICA, ⁴Transplant Surgery, University of Cincinnati, cincinnati/UNITED STATES OF AMERICA, ⁵, Denver Nephrologists PC, Denver/CO/UNITED STATES OF AMERICA, ⁶Dept Of Surgery, Catholic University, Rome/ITALY, ⁷Organ Transplantation, Swedish Medical Center, Seattle/WA/UNITED STATES OF AMERICA, ⁸, Bristol-Myers Squibb, Hopewell/NJ/UNITED STATES OF AMERICA, ⁹, Bristol-Myers Squibb, Princeton/NJ/UNITED STATES OF AMERICA, ¹⁰Nephrology, University of Barcelona, Hospital Universitari de Bellvitge, Barcelona/SPAIN

Body:
Introduction: Strategies to avoid both CNIs and steroids in the same regimen have not been successful in de novo kidney transplant patients. This study was designed to assess 2 belatacept-based regimens vs a tacrolimus-based regimen in kidney transplant recipients as potential CNI- and steroid-avoiding immunosuppression. Methods: This is a Phase 2, 1-year, randomized, open-label, exploratory, multicenter study in EBV seropositive adults receiving a primary kidney transplant. Patients were randomized 1:1:1 to receive belatacept (bela)+MMF, bela+sirolimus (SRL), or tacrolimus (TAC)+MMF. Belatacept was initiated at 1 mg/kg and was maintained at 5 mg/kg after 6 months. All patients received induction with 4 doses of thymoglobulin (6 mg/kg max) and corticosteroid pretreatment. The primary endpoint was the incidence of acute rejection (AR) at 6 months. Results: 89 patients were randomized and transplanted; 51% received an organ from a deceased donor.

Outcome (Month 12 unless noted)	Bela+MMF n = 33	Bela+SRL n = 26	TAC+MMF n = 30
Acute rejection at Month 6, n (%)	4 (12)	1 (4)	1 (3)
Acute rejection at Month 12, n (%)	5 (15)	1 (4)	1 (3)
Patient and graft survival, n (%)	30 (91)	24 (92)	30 (100)
Death, n (%)	1 (3)	0	0
Graft loss, n (%)	2 (6)	2 (8)	0
Mean cGFR, mL/min/1.73 m2 (SD)	64 (27)	62 (31)	54 (15)
CNI-free and steroid-free patients, n (%)	24 (73)	18 (69)	1 (3)
Steroid-free patients, n (%)	24 (73)	20 (77)	28 (93)
Serious infections, n (%)	7 (21)	4 (15)	5 (17)
Mouth ulceration, n (%)	2 (6)	6 (23)	0
Tremors, n (%)	1 (3)	0	7 (23)

Most AR occurred within the first 3 months. 2 cases of skin cancer were reported (n = 1 TAC+MMF; n = 1 bela+SRL). Overall safety was comparable across groups. Conclusions: Primary immunosuppression with belatacept may enable CNI- and steroid-avoidance in recipients of living and deceased standard criteria donor kidneys, with acceptable rates of AR and improved renal function relative to a tacrolimus-based regimen at 12 months.

Disclosure: All authors have declared no conflicts of interest.