Everolimus and reduced calcineurin inhibitor therapy in pediatric liver transplant recipients: Results from a multicenter, prospective study

In a 24-month, multicenter, single-arm, prospective study, 56 pediatric liver transplant patients with or without basiliximab induction were converted at 1-6 months post-transplant from standard calcineurin inhibitor (CN) therapy (± mycophenolic acid), to everolimus with reduced exposure to CNI (tacrolimus n=50, cyclosporine n=6). Steroid therapy was optional. Recruitment was stopped prematurely due to high rates of PTLD, treatment-related serious infections leading to hospitalization and premature study drug discontinuation. Subsequently, patients aged <7 years reverted to local standard-of-care immunosuppression. Mean tacrolimus concentration was above or near the upper end of the maintenance target range (2-5 ng/mL) until after month 6 post-enrollment. The primary variable, mean (SD) change in eGFR from baseline to month 12 (last observation carried forward), was +6.2 (19.5) mL/min/1.73 m2. Two patients experienced treated biopsy-proven acute rejection. No graft losses or deaths occurred. PTLD occurred in five patients (8.9%) (3/25 [12.0%] patients <2 years, 2/31 aged 2-18 years [6.5%]). Adverse events, serious adverse events, and discontinuation due to adverse events were reported in 100.0%, 76.8%, and 44.6% of patients, respectively. In conclusion, everolimus with reduced CNI improved renal function while maintaining antirejection potency in pediatric liver transplant patients but safety outcomes suggest that patients were overimmunosuppressed.