USE OF MTOR INHIBITORS AND MPA I

R. Hené¹, R.M. Langer², S. Vitko³, M. Christiaans⁴, K. Ciechanowski⁵, E. Cassuto⁶, J. Dominguez⁷, J. Wyzgal⁸, A.C. Henriques⁹, J. Pascual^10
1Nephrology, Universitair Medisch Centrum Utrecht, Utrecht/NETHERLANDS, ²Transplantation And Surgery, Semmelweis University, Budapest/HUNGARY, ³, Institute of Clinical and Experimental Medicine, Prague/CZECH REPUBLIC, ⁴, Academisch Ziekenhuis Maastricht, Maastricht/NETHERLANDS, ⁵, Klinika Chirurgii Ogolnej i Transplantacyjnej, Szczecin/POLAND, ⁶Service De Néphrologie, Hôpital Pasteur, Nice/FRANCE, ⁷, Hospital Dr. Sotero del Rio, Santiago/CHILE, ⁸, Szpital Kliniczny Dzieciatka Jezus - Centrum Leczenia Obrazen, Warszawa/POLAND, ⁹, Hospital Geral de Santo Antonio, Porto/PORTUGAL, ¹⁰Dept Of Nephrology, Hospital del Mar, Barcelona/SPAIN

Body: Introduction: Everolimus (EVR) is a proliferation signal inhibitor (PSI) with potent immunosuppressant effects. Studies have demonstrated that EVR allows for minimization of calcineurin inhibitors (CNI) exposure with preserved renal function (RF), while maintaining efficacy and tolerability comparable to standard CNI exposure, in renal transplant recipients (RTxR). The magnitude of CNI minimization is still under investigation, especially when EVR is combined with Tac. Here we report the results from ASSET, a 12 month (M), prospective, multinational, open-label study designed to explore the efficacy and safety of two reduced Tac exposure regimens in combination with EVR in de novo RTxR. Methods: 228 RTxR were randomized (1:1) within 24h post-transplantation (Tx) to either of the two arms: EVR with low dose (LTac) or EVR with very low dose (VLTac) arm. All patients received basiliximab and steroids. For the first 3 months all patients received EVR (1.5 mg bid, C0 3–8ng/mL) and Tac (0.1 mg/kg/day, C0 4–7 ng/mL) therapy. The LTac group continued the initial regimen unchanged whereas the VLTac group received Tac targeted to C0 1.5–3ng/mL until M12. Study endpoints were efficacy failure (BPAR, graft loss, death, loss to follow-up) from M4–12, RF and safety at M12. Results: ITT-population of 224 RTxR (VLTac, 107; LTac, 117) had comparable baseline characteristics. The mean Tac levels were within target range during first 3M in both arms, afterwards VLTac arm was slightly above the upper range (mean C0 of 3.5, 3.4 and 3.4 ng/mL at M6, 9, and 12). Daily EVR dose of 3–3.5 mg was necessary to reach the defined range. Overall rates of efficacy failure including BPAR from M4–12 were low and comparable in both arms (Table). Non-inferiority of VLTac to LTac treatment for BPAR was achieved at a pre-defined non-inferiority margin of 8% between M4 and 12 post-Tx. Two patients in VLTac arm and one patient in LTac arm had a BPAR event after M4. At M12, cGFR in VLTac and LTac arms were 57.1±19.5 and 51.7±20 mL/min/1.73m² (+5.34, p=0.0299; one-sided at a-level 0.025). Study discontinuation due to AEs occurred in 14% of VLTac and 11% LTac patients. Conclusion: EVR allowed for a substantial minimization of Tac (VLTac trough of 3.4 ng/mL at M12) in de novo RTxR and demonstrated comparable efficacy as LTac. Incidence of BPAR after M4 was low in both groups. Safety and tolerability of EVR was comparable to earlier studies. Table. Efficacy failure (M4–12), ITT-population

Disclosure: All authors have declared no conflicts of interest.