Early conversion of pediatric kidney transplant patients to everolimus with reduced tacrolimus and steroid elimination: Results of a randomized trial.

In a 12-month, multicenter, open-label study, 106 children were randomized at 4 to 6 weeks after kidney transplantation to switch to everolimus with reduced TAC (EVR/rTAC) and steroid elimination from month 5 posttransplant or to continue standard tacrolimus with mycophenolate mofetil (sTAC/MMF) and steroids. The cumulative incidence of a co-primary efficacy end point (biopsy-proven acute rejection [BPAR], graft loss, or death from randomization to month 12) was 10.3% with EVR/rTAC and 5.8% with sTAC/MMF (difference 4.4%; P = .417). BPAR occurred in 9.6% and 5.6% of patients, respectively. Patient and renal allograft survival were 100%. The co-primary end point of mean estimated glomerular filtration rate at month 12 was 76.2 mL/min/1.73 m2 with EVR/rTAC and 72.5 mL/min/1.73 m2 for sTAC/MMF (difference 3.8 mL/min/1.73m2 ; P = .49). One EVR/rTAC patient developed posttransplant lymphoproliferative disease. Longitudinal growth and sexual maturation were equivalent between groups. The randomized drug regimen was discontinued in 34.6% and 13% of patients in the EVR/rTAC and sTAC/MMF groups, respectively (P = .024), and discontinued due to adverse events/infections in 25.0% and 11.1% of patients (P = .062). In conclusion, early conversion of pediatric kidney transplant patients from TAC, MMF, and steroids to EVR/rTAC and steroid withdrawal maintains immunosuppressive efficacy and preserves renal function.

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.