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.