Survival in Lung Transplant Recipients on a Calcineurin Free Regimen: Is It Possible?

Abstract

Calcineurin inhibitors (CNI) are the cornerstone of immunosuppression in lung transplantation. The International Heart and Lung Transplant registry data estimates that almost 99% of patients are on a CNI-based immunosuppression regimen. The population of lung transplant (LTx) recipients not on a calcineurin inhibitor is exceedingly rare and their outcomes have not been previously examined in a systematic way. An IRB-approved, retrospective, observational, cohort study of LTx recipients who received CNI-free, everolimus (EVR)-based immunosuppression at the University of Colorado from January 1, 1995 - October 1, 2019. The health system's electronic medical records was queried to identify and collect data on eligible LTx recipients. All continuous variables are presented as median(range). Seven of 12 were single LTx (ILD, COPD), five were bilateral LTx,(ILD, COPD, CF) and one was a re-transplant. The majority (8/12) of patients were transitioned to CNI-free, EVR-based immunosuppression due to renal insufficiency, 3/12 due to metastatic cancer, and 1/12 due to both renal failure and cancer. Five of 12 were maintained on three agents (EVR, corticosteroid, and either methotrexate or azathioprine) and the others were on corticosteroids with EVR alone. The median time to transition to CNI-free immunosuppression was 8.8 (2.3 to 21.3) years. Median age at CNI cessation was 67 years old (40-72 years old). Median survival on CNI-free immunosuppression for all comers was 1.6 years with median survival in the deceased cohort (n=8) of 1 year (4 days to 4.6 years) and median survival in the living cohort (n=4) of 2.1 years (1.2 years to 8.2 years). At least three patients were treated with high dose steroids for presumed acute rejection after stopping the CNI. This review demonstrates that in certain situations withdrawal of CNI and transition to CNI-free, EVR- based immunosuppression may result in durable patient survival. Larger multicenter cohort analysis may be the next step in understanding the safety, efficacy and role of CNI-free immunosuppression, as equipoise would be impossible to achieve in a randomized controlled trial.