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

American Journal of Transplantation. 2019;19(11):3018-3034


TRANSFORM was a 24-month, prospective, open-label trial in 2037 de novo renal transplant recipients (RTxRs) randomized (1:1) within 24 hours of transplantation to receive everolimus (EVR) with reduced-exposure calcineurin inhibitor (EVR+rCNI) or mycophenolate with standard-exposure CNI (MPA+sCNI). 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) <50 mL/min/1.73 m2 was achieved at Month 24 (47.9% vs 43.7%; difference = 4.2%; 95% confidence interval [CI] = -0.3, 8.7; P = 0.006). Mean eGFR was stable up to Month 24 (52.6 vs 54.9 mL/min/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<0.0001). 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 24 months. This article is protected by copyright. All rights reserved.

CET Conclusion

Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, The Royal College of Surgeons of England.
This manuscript reports 24-month follow-up from the TRANSFORM study. 2037 de novo renal transplant recipients were randomized to everolimus and reduced dose CNI, or to MMF and standard-dose CNI. No difference in efficacy was seen, with similar eGFR and BPAR rates in both arms. As might be expected from previous mTORi studies, medication discontinuation due to adverse events was higher in the everolimus arm. However, infection rates, particularly for viral infections, were lower with everolimus. This is a large multicenter study that is well conducted and reported. Whilst it doesn’t offer a compelling reason to use everolimus over a standard Tac/MMF regimen, it certainly supports it as an alternative strategy with equivalent efficacy. Choice of regimen is likely to be dictated by side-effect profile.

Methodological quality

Jadad score : 3
Allocation concealment : NO

Study details

Aims : This study aimed to assess the two-year outcomes of patients from the TRANSFORM study receiving everolimus (EVR) with reduced‐exposure calcineurin inhibitors (CNI) (EVR+rCNI) vs mycophenolic acid (MPA) with standard‐exposure CNI (MPA+sCNI).
Interventions : This is a post-hoc analysis of the TRANSFORM (TRANSplant eFficacy and safety Outcomes with an eveRolimus‐based regiMen) trial, which compared the effect of renal transplant recipients receiving everolimus (EVR) with reduced‐exposure calcineurin inhibitor (EVR + rCNI) or mycophenolate with standard‐exposure CNI.
Participants : 2037 de novo kidney transplant patients from the TRANSFORM study (n=1022 EVR+rCNI; n=1015 MPA+sCNI).
Outcomes : The primary outcome measured was a binary composite of treated biopsy-proven acute rejection (tBPAR) or suboptimal kidney function (eGFR 50 ml/min per 1.73m2) at 24 months post-transplant. The secondary outcome measured was a composite of efficacy failure and included tBPAR, graft loss, or death.
Follow up : 24 months


Publication type : Randomised Controlled Trial
Organ : Kidney
Language : English
MeSH terms : kidney transplantation