Calcineurin Inhibitor Replacement With Mammalian Target of Rapamycin (mTOR) Inhibitor Following Lung Transplantation

Calcineurin inhibitors (CNIs) are the cornerstone of lung transplant immunosuppression but are associated with nephrotoxicity and other adverse effects. Although dose reduction and combination with Sirolimus, a mammalian target of rapamycin inhibitor (mTORi), have been explored, full conversion to Sirolimus remains uncommon. This study describes the characteristics and outcomes of lung transplant recipients who underwent complete CNI withdrawal and conversion to Sirolimus.

This retrospective case series included 52 lung transplant recipients transitioned to Sirolimus-based immunosuppression between 2010 and 2021. Data on demographics, transplant characteristics, immunosuppression, and outcomes were collected from electronic medical records.

The cohort included 31 males (59.6%) with a median age of 58.4 years (IQR 52.3-63.5). The primary indication for CNI withdrawal was renal dysfunction (73.1%). Sirolimus discontinuation occurred in 69.2%, most commonly due to edema (25.0%), lung toxicity (19.4%), rejection (19.4%), and surgical needs (22.2%). Clinically significant rejection occurred in 13.5%, with four patients progressing to chronic lung allograft dysfunction (CLAD) and two deaths. Sixteen patients (30.8%) tolerated CNI withdrawal for over a year.

Full conversion from CNI to Sirolimus is poorly tolerated due to side effects and has a high incidence of rejection. Further studies are needed to optimize patient selection and risk mitigation strategies.