Incidence of Wound Events and Lymphocele Formation with De Novo Everolimus Use: The Results of 3 Randomized Clinical Trials

Abstract

Introduction: The antiproliferative effect of everolimus (EVR) is associated with influencing rates of wound events. Targeting lower exposure of EVR with low exposure to CNIs can preserve efficacy while minimizing events, but other factors that impact events and timing is not well-described. Data was pooled across 3 RCTs in de novo renal transplantation to understand these associations. Methods: Data was pooled from 3 Randomized Clnical Trials: Two compared EVR 1.5 or 3.0 mg/d (levels collected) vs MPA with standard dose cyclosporine (CsA). The other compared the two controlled doses of EVR (0.75 mg bid, targeted to 3-8 ng/ml or 1.5 mg bid, goal 6-12 ng/ml) with reduced-dose CsA vs MPA with standard CsA. Investigatorreported rates of wound events were compared at 30, 60, and 90 days post-operatively with subgroup analysis of those with baseline diabetes and increased BMI, and those requiring a bedside or surgical intervention. The association between EVR level and wound risk in a time dependent model for EVR 1.5 was also evaluated. Results: Of the 1996 patients, 16.6, 21.8,and 14.3% of the EVR 1.5, EVR 3.0,and MPA patients had a reported wound event at 90 days, respectively. There was no difference in patient or graft survival among groups at 1 and 2 years.Table: [Wound Healing Events]EVR targeted to 3-8 ng/ml with reduced exposure to CsA allows for similar rates and timing of wound events compared to MPA. The timedependent analysis showed that diabetes and high BMI were associated with higher risk(HR=1.58 & 1.05; p=0.06 & 0.01, respectively), but EVR levels were not associated with risk of wound events. Conclusion: This is the most comprehensive evaluation of de novo use of EVR in kidney transplantation in the development of wound ‘events’. At the recommended EVR goal of 3-8 ng/ml, the overall incidence of wound events was not increased compared to MPA. The results of this review prompt the discussion of further de novo use of EVR in kidney transplantation to improve long-term graft survival and minimize immunosuppressive toxicity.