Everolimus-facilitated calcineurin inhibitor reduction in Asian de novo kidney transplant recipients: 2-year results from the subgroup analysis of the TRANSFORM study

Abstract

Objective: We analyzed the efficacy and safety of an everolimus with reduced-exposure calcineurin inhibitor (EVR+rCNI) versus mycophenolic acid with standard-exposure CNI (MPA+sCNI) regimen in Asian patients from the TRANSFORM study.

Methods: In this 24-month, open-label study, de novo kidney transplant recipients (KTxRs) were randomized (1:1) to receive EVR+rCNI or MPA+sCNI, along with induction therapy and corticosteroids.

Results: Of the 2037 patients randomized in the TRANSFORM study, 293 were Asian (EVR+rCNI, N = 136; MPA+sCNI, N = 157). At month 24, EVR+rCNI was noninferior to MPA+sCNI for the binary endpoint of estimated glomerular filtration rate (eGFR) < 50 ml/min/1.73 m2 or treated biopsy-proven acute rejection (27.0% vs. 29.2%, P = .011 for a noninferiority margin of 10%). Graft loss and death were reported for one patient each in both arms. Mean eGFR was higher in EVR+rCNI versus MPA+sCNI (72.2 vs. 66.3 ml/min/1.73 m2 , P = .0414) even after adjusting for donor type and donor age (64.3 vs. 59.3 ml/min/1.73 m2 , P = .0582). Overall incidence of adverse events was comparable. BK virus (4.4% vs. 12.1%) and cytomegalovirus (4.4% vs. 13.4%) infections were significantly lower in the EVR+rCNI arm.

Conclusion: This subgroup analysis in Asian de novo KTxRs demonstrated that the EVR+rCNI versus MPA+sCNI regimen provides comparable antirejection efficacy, better renal function, and reduced viral infections (NCT01950819).

Keywords: everolimus; kidney transplant; reduced calcineurin inhibitor; reduced cyclosporine; reduced tacrolimus.

Conflict of interest statement

Yoshihiko Watarai has received consulting honoraria and travel grants from Novartis, Astellas, and Chugai Pharma. Romina Danguilan has received speaker's honoraria from Novartis, Astellas, MSD, Sanofi, Macropharma, and Pharmalink. Concesa Casasola, Shen‐Shin Chang, Prajej Ruangkanchanasetr, Terence Kee, Hin Seng Wong, Takashi Kenmochi, Angel Joaquin Amante, Kuo‐Hsiung Shu, Atiporn Ingsathit, Duck Jong Han, and Myoung Soo Kim have no conflict of interest. Peter Bernhardt and Maria Pilar Hernandez‐Gutierrez are employees of Novartis.

© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Figures

FIGURE 1

Patient disposition. Abbreviations: EVR, everolimus; MPA, mycophenolic acid; rCNI, reduced‐exposure calcineurin inhibitors; sCNI, standard‐exposure CNI

FIGURE 2

Trough concentrations of (A) everolimus (B) tacrolimus, and (C) cyclosporine (safety analysis set). Abbreviations: C0, trough level; CsA, cyclosporine; EVR, everolimus; M, month; MPA, mycophenolic acid; rCNI, reduced‐exposure calcineurin inhibitors; sCNI, standard‐exposure CNI; TAC, tacrolimus; Tx, transplant; W, week. Shaded area represents target trough levels

FIGURE 3

Estimated GFR during the study (on‐treatment analysis). Abbreviations: BL, baseline; eGFR, estimated glomerular filtration rate; EVR, everolimus; M, month; MDRD4, 4‐Modification of Diet in Renal Disease; MPA, mycophenolic acid; rCNI, reduced‐exposure calcineurin inhibitors; sCNI, standard‐exposure CNI; Tx, transplant; W, week

FIGURE 4

Multivariate analysis for patients with eGFR below or above 50 ml/min/1.73 m2 at month 24. Abbreviations: AR, acute rejection; ECD, expanded criterial donor; eGFR, estimated glomerular filtration rate; LD, living donor; M, month; SCD, standard criteria donor