The Successful Evolution of Everolimus Based Immunosuppression (IS) in a Large Lung Transplant (LTx) Cohort: 14 Years Experience

PURPOSE: EVE has proven benefits when prescribed post heart or kidney transplantation. The role of EVE is less well defined in LTx. We reported our experience with EVE over a 14-year period. METHODS: Single-center retrospective cohort study evaluating 124 adult LTx recipients initiated on EVE between 2005 and 2018 for calcineurin inhibitor (CNI) minimization / elimination. Data collected include demographics, prescribing patterns, mean EVE dose/ trough levels, adverse events and clinical parameters. RESULTS: 124 LTx recipients [mean age 51 ±15 years, 70% male, 82% BSLTx, mean days post LTx = 1059 ± 1374 days (range 12 - 7289)]. 38% patients switched less than 12 months post LTx. Patients were followed for a mean of 1415 ± 1282 days after initiation (range = 49 - 4826 days). LTx diagnosis: COPD 35%, ILD 22%, CF 22%, PAH 8%. Main indications: renal impairment (79%), malignancy (8%), neurotoxicity (5%), rejection (4%). Initiation of EVE allowed significant reduction of CNI levels. 121/124 patients (98%) of patients utilised CNIs at the time of switch, 78/124 (63%) one-week post initiation, 49/124 (39%) 3 months' post switch and 34/124 (27%) at last follow up. TAC levels were reduced from a mean level of 9.0 ± 2.5 mg/L (one-month pre-switch) to 7.0 ± 2.4 mg/L (time of switch) to 5.0 ± 2.2 mg/L (3 months' post switch). Median (range) EVE dose: 2.5 mg (0.25 - 10.0 mg) and mean (±SD) trough level: 5.9 ± 2.9 mg/L at 1 week and 5.08 ± 1.94 mg/L at 3 months. Pre-switch to EVE, there was a significant fall in mean creatinine clearance (CrCL) of 22 mL/min (p<0.001) between LTx and one-year post-LTx. The observed fall in mean CrCL between LTx and commencement of EVE was 33 mL/min (p<0.001). EVE caused a significant improvement in mean CrCL from date of switch to 3 months post switch (14 mL/min, p < 0.001) and 10 mL/min (p=0.004) higher at final follow-up. There was no significant change in CrCL between 3 months and 12 months' post switch. There were no deaths from renal failure or significant changes in proteinuria. 62/124 (50%) are now deceased (primarily CLAD, 31%). 38/124 (31%) discontinued EVE [n = 16 drug intolerance, n =11 accelerated lung function decline]. Changes in lipid or haematological profiles were not significant. CONCLUSION: Conversion of CNI-based IS to EVE-based IS is generally safe and efficacious for improving renal outcomes and neurotoxicity but not CLAD or malignancy.