Two-year outcomes in de novo renal transplant recipients receiving everolimus-facilitated calcineurin inhibitor reduction regimen from the TRANSFORM study.

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TRANSFORM (TRANSplant eFficacy and safety Outcomes with an eveRolimus-based regiMen) was a 24-month, prospective, open-label trial in 2037 de novo renal transplant recipients randomized (1:1) within 24hours of transplantation to receive everolimus (EVR) with reduced-exposure calcineurin inhibitor (EVR+rCNI) or mycophenolate with standard-exposure CNI. Consistent with previously reported 12-month findings, noninferiority of the EVR+rCNI regimen for the primary endpoint of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR)<50mL/min per 1.73m2 was achieved at month 24 (47.9% vs 43.7%; difference=4.2%; 95% confidence interval=-0.3, 8.7; P=.006). Mean eGFR was stable up to month 24 (52.6 vs 54.9mL/min per 1.73m2 ) in both arms. The incidence of de novo donor-specific antibodies (dnDSA) was lower in the EVR+rCNI arm (12.3% vs 17.6%) among on-treatment patients. Although discontinuation rates due to adverse events were higher with EVR+rCNI (27.2% vs 15.0%), rates of cytomegalovirus (2.8% vs 13.5%) and BK virus (5.8% vs 10.3%) infections were lower. Cytomegalovirus infection rates were significantly lower with EVR+rCNI even in the D+/R- high-risk group (P<.0001). In conclusion, the EVR+rCNI regimen offers comparable efficacy and graft function with low tBPAR and dnDSA rates and significantly lower incidence of viral infections relative to standard-of-care up to 24months. Clinicaltrials.gov number: NCT01950819.