Purpose: Everolimus (EVR) facilitated calcineurin inhibitor (CNI) reduction has shown improved renal function (RF) without compromising efficacy in adult liver transplant recipients (LTxR). Here we present Month (M) 12 efficacy, including RF, and safety outcomes in pediatric (p) LTxR receiving EVR+reduced (r) CNI (tacrolimus [rTAC]/cyclosporine [rCsA]).

Methods: H2305 (NCT01598987) was a 24M, multicenter, open-label, single-arm study in 56 pLTxR (≥1M and <18years [y]; stratified by age: <2y [n=25] and 2-<18y [n=31]) on CsA/TAC±mycophenolate±steroids between M1 to M6 post-Tx who were switched to EVR (trough levels [C0] 3-8ng/mL)+rTAC (n=50, C0 M1–M3:3-6ng/mL; after M3:2-5ng/mL)/rCsA (n=6, C0 M1–M3:50-150ng/mL; after M3:25-100ng/mL)±steroids. Primary objective was evolution of RF (eGFR; Schwartz formula) from baseline (BL) to M12. Other objectives were composite efficacy failure (CEF; treated biopsy-proven acute rejection [tBPAR], graft loss, or death) and safety at M12. Based on data monitoring committee recommendations, recruitment was prematurely stopped due to post-Tx lymphoproliferative disease (PTLD), serious infections, and treatment discontinuation. Patients <7y were switched to standard-of-care.

Results: Mean age at BL was 4.9y. Overall, C0 for EVR, TAC, and CsA were within the target ranges up to M12 for most of pLTxR. For mean EVR C0, a trend towards the lower end of target range was observed. Mean C0 of TAC and CsA were near the upper limit of target range till M6 and M3, respectively. Half of pLTxR received basiliximab. Steroid dose decreased over time but was higher in patients <2y. Mean eGFR improved from BL to M12 in overall population and in both the age groups (table). At M12, CEF was reported in one patient (tBPAR). Treatment discontinuations, incidence of infections, CMV, EBV, and PTLD were higher in <2y than 2-<18y patients. No negative effect on growth and sexual development was noted.

Conclusions: EVR+rCNI improved RF while maintaining antirejection potency in pLTxR, but safety outcomes suggest overimmunosuppression.

CITATION INFORMATION: Weymann A, Ganschow R, Ericzon B, Dhawan A, Sharif K, Martzloff E.-D, Rauer B, Ng J, Lopez P. Efficacy and Safety of Everolimus with Reduced Tacrolimus or Cyclosporine in Pediatric Liver Transplant Recipients: 12-Month Results from H2305 Study. Am J Transplant. 2017;17 (suppl 3).

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