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

Abstract

Calcinuerin inhibitor (CNI) based immunosuppression (IS) regimens remain the cornerstone of IS protocols post lung transplantation (LTx). Everolimus (EVE) has been used to augment IS in LTx patients or as a CNI minimization/ elimination agent in those with renal impairment or recurrent CMV infection. There is limited evidence to support EVE based IS regimens and the impact on progression to chronic lung allograft dysfunction (CLAD). The primary aim was to compare patients who remained on CNI-based IS to those who switched to EVE-based IS and assess the impact of EVE-based IS on time to CLAD and ultimately survival. Single centre retrospective study of 91 patients who were initiated on EVE from 1550 consecutive LTx recipients between 1993 and 2018. Each EVE patient was matched with a patient who remained on CNI-based IS. Criteria for matching included indication for LTx, gender, LTx procedure and age at LTx. A survival analysis was performed in the EVE cohort. 182 LTx recipients [91 EVE & 91 CNI-based IS, mean age 51 ±15 years, 70% male, 82% BSLTx, LTx diagnosis: COPD 35%, ILD 22%, CF 22%, PAH 8%]. The incidence of CLAD was similar across the groups (51% EVE-based vs 48% CNI-based). Patients with CLAD at initiation of EVE had a 3.6 times higher risk of death than those without CLAD [HR 3.60, 95% CI: 2.16 - 6.01, p = 0.0001]. However there was no significant difference in the risk of developing CLAD between EVE-based IS and CNI-based IS [HR 1.05, 95% CI: 0.65 - 1.71]. The incidence of the RAS phenotype of CLAD was higher in the EVE-based group (56% EVE-based vs 39%- CNI-based) but not significant. The risk of death is not significant between EVE-based IS and CNI-based IS from time of switch [HR 1.22, 95% CI: 0.77 - 1.88]. The median days from CLAD to death was significantly higher (p = 0.01) in the EVE-based IS group (1127, IQR: 504 - 2210) compared to the CNI-based group (427, IQR: 236 - 1229). The survival analysis noted a higher mortality with 1) Earlier initiation post LTx (2% / month closer to LTx, 95% CI 1.0 - 3.0%, p = 0.001), 2) Increasing age at initiation (3% /year of age, 95% CI, 0 - 5%, p = 0.029). 3) Diabetes at the time of initiating EVE (HR 2.74 [1.48 - 5.09], p = 0.001). EVE-based IS can be successfully utilized for second-line IS for CNI minimization / elimination and was not associated with an increase in CLAD incidence or CLAD related mortality.