Tolerability of everolimus-based immunosuppression in maintenance liver transplant recipients

Background: The aim of this study was to evaluate the tolerability of the conversion from calcineurin inhibitor (CNI) to everolimus (ERL) in maintenance liver transplant (LT) recipients. Methods: From January 2005 to March 2008, ERL was introduced after LT as maintenance immunosuppressive therapy because of (i) de novo or recurrent cancer after LT, (ii) pre-existing liver carcinoma on the liver explant or (iii) CNI toxicity. CNI dosage was progressively reduced until discontinuation. Results: The study population included 94 patients, of mean age 57 +/- 10. The mean delay between LT and ERL introduction was 5 +/- 5 yr. After a mean follow-up of 12 +/- 7 months, 70% of the patients did present at least one side effect. The mean trough level of ERL was 6 mu g/L at the end of follow-up. Main side effects included hyperlipidemia (37%), dermatitis (19%), mucositis (15%), and proteinuria (18%). Biopsy-proven acute rejection occurred in 9% of patients. Global ERL discontinuation rate was 21% (16% because of side effects). Conclusions: The results of our experience indicate that conversion to ERL is associated with adverse effects in 70% of patients leading to drug discontinuation in 16% (and amenable to dose reduction in the remainders). Longer follow-up periods are necessary to capture the impact of ERL fully on renal function and survival in cancer patients.