Rescue Everolimus Post Lung Transplantation is Not Associated With an Increased Incidence of CLAD or CLAD-Related Mortality

Abstract

Everolimus (EVE) has been used as a calcineurin inhibitor (CNI) minimization/ elimination agent or to augment immunosuppression in lung transplant recipients (LTR) with CNI-induced nephrotoxicity or neurotoxicity. The long-term evidence for survival and progression to chronic lung allograft dysfunction (CLAD) is lacking. The primary aim was to compare survival outcomes of LTR starting EVE-based immunosuppression with those remaining on CNI-based regimens. The secondary outcomes being time to CLAD, incidence of CLAD and the emergence of obstructive (BOS) or restrictive (RAS) phenotypes. Single center retrospective study of 91 LTR starting EVE-based immunosuppression matched 1:1 with LTR remaining on CNI-based immunosuppression. On multivariate analysis, compared to those remaining on CNI-based immunosuppression, starting EVE was not associated with poorer survival [HR 1.04, 95% CI: 0.67-1.61, p = 0.853], or a statistically significant faster time to CLAD [HR 1.34, 95% CI: 0.87-2.04, p = 0.182]. There was no difference in the emergence of CLAD (EVE, [n = 57, 62.6%] vs. CNI-based [n = 52, 57.1%], p = 0.41), or the incidence of BOS (p = 0.60) or RAS (p = 0.16) between the two groups. Introduction of EVE-based immunosuppression does not increase the risk of death or accelerate the progression to CLAD compared to CNI-based immunosuppression.

Keywords: bronchiolitis obliterans syndrome; calcineurin inhibitor; chronic lung allograft dysfunction; everolimus; lung transplantation; restrictive allograft syndrome.