Promising Outcomes after Long-Term Therapy with Everolimus: Two-Years Results of the CERTIC Registry

Purpose Everolimus (EVR) is registered for prevention of acute rejection in heart transplant (HT) recipients. Its mechanism of action provided additional rationale to improve several HT-related comorbidities in maintenance patients, such as malignancies, allograft vasculopathy, or renal insufficiency. However, evidences in this setting are sparse and often related to single-center reports. We thus designed the CERTIC registry to collect prospective multicenter data on safety and efficacy of long-term use of EVR in de novo and in maintenance patients with high comorbidity profile. Methods and Materials Between 2008 and 2010, recipients of renal or HT who were on therapy with EVR for at least 6 months were eligible to enter this 5-year registry. Herein we report analysis of two years follow-up data about survival, malignancies onset and outcome, and renal function in the HT recipients’ cohort. Results 402 HT recipients (of whom 24% started EVR as a de novo strategy) were enrolled. 307 (76%) patients started EVR 8±5y after HT, following renal dysfunction (55%), allograft vasculopathy (21%), or malignancies (13%). Overall, including the period of EVR treatment before study entry, patients had been on EVR for 4±1y. Despite the high prevalence of comorbidities, a low number of fatal events have been recorded: 3 in de novo (1.6% yearly death rate) and 23 in maintenance patients (3.7% yearly death rate). Rate of new-onset malignancy was 1.8-2.8% per year of EVR treatment, accounting for 7 solid organ and 9 skin cancers. No PTLDs and Kaposi’s sarcoma were recorded. Renal function was overall stable during EVR treatment. Conclusions By picturing real-life clinical practice, this large prospective registry shows promising survival rates in de novo patients and in those with high-risk comorbidities, including malignancies. Renal function seems to be effectively preserved, unless EVR is started too late after HT.