Background: The TRANSFORM study has shown comparable efficacy-safety of everolimus with reduced calcineurin inhibitor (EVR+rCNI) versus mycophenolic acid and standard CNI (MPA+sCNI) treatment in de novo kidney transplant recipients (KTxRs). Here we present 24-month (M) data of the Asian race subgroup from the TRANSFORM study.
Methods: In this open-label study, KTxRs were randomized (1:1) to receive EVR+rCNI or MPA+sCNI; plus induction therapy and steroids. The primary composite endpoint was estimated glomerular filtration rate [Modification of Diet in Renal Disease] (eGFR [MDRD])<50 mL/min/1.73 m² or treated biopsy-proven acute rejection (tBPAR). Other endpoints were composite efficacy failure (CEF: tBPAR, graft loss or death), evolution of eGFR, and safety. A multivariate analysis and a univariate analysis were performed retrospectively to further evaluate the factors affecting clinical outcomes.
Results: Of 2037 randomized patients, 293 were of Asian race (EVR+rCNI: 136; MPA+sCNI: 157). The trough concentration (C0) for tacrolimus (up to 41.8% vs 27.8%) and cyclosporine (up to 63.2% vs 22.7%) was mostly above the target level in EVR+rCNI arm. At M24, EVR+rCNI arm was non-inferior to MPA+sCNI for the composite of eGFR (MDRD)<50 mL/min/1.73 m² or tBPAR (27.0% vs 29.2%, P=0.011 for non-inferiority [NI] margin of 10%). Incidence of CEF was non-inferior in EVR+rCNI versus MPA+sCNI arm (9.0% vs 16.9%, P<0.001 for NI margin of 10%) and was driven by tBPAR (EVR+rCNI: 8.2% vs MPA+sCNI: 15.7%, P=0.068). Graft loss and death were reported for one patient each in both the treatment arms. Mean eGFR was significantly higher inEVR+rCNI versus MPA+sCNI (72.2 vs 66.3 mL/min/1.73 m², P=0.041) (Figure). Multivariate analysis showed increasing donor age in EVR+rCNI (P=0.002) and MPA+sCNI arms (P<0.001), while deceased donor transplant (standard criteria donor, P=0.020) and use of cyclosporine (P=0.038) in MPA+sCNI arm as independent factors significantly impacting renal function. BMI of KTxRs had no effect on the clinical outcomes except for wound healing event (BMI<30 kg/m²: EVR+rCNI=26.3% vs MPA+sCNI=16.0%; P=0.040). Overall incidence of adverse events was comparable, with significantly lower incidence of BK virus (4.4% vs 12.1%) and cytomegalovirus infection (4.4% vs 13.4%) reported in EVR+rCNI arm.
Discussion: Better efficacy (CEF: 9.0% vs 18.0%; tBPAR: 8.2% vs 12.8%, respectively) and renal function (72.2 vs 58.2 mL/min/1.73 m²) observed in EVR+rCNI arm of the Asian subgroup versus overall population may be attributed to the higher proportion of living donors (84.6% vs 50.0%), younger recipients (43.3 vs 48.8 years) and donors (42.7 vs 48.3 years).
Conclusions: The M24 results from the subgroup analysis of the TRANSFORM study demonstrate that both treatment regimens in Asian KTxRs provide comparable antirejection efficacy with significantly better renal function and reduced viral infections in EVR+rCNI arm, with no new or unexpected safety concerns.