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Clinical Outcomes of Using mTOR Inhibitors with Reduced Dose of Calcineurin Inhibitors in Lung Transplant Recipients: A Single Center Experience

M. Frawley1, J. Leedy1, A. James1, A. Salter1, V. Rusanov2

1Department of Pharmacy, UAB Hospital, Birmingham, AL, 2Division of Pulmonary, Allergy, and Critical Care Medicine, UAB Hospital, Birmingham, AL

Meeting: 2019 American Transplant Congress

Abstract number: C349

Keywords: Immunosuppression, Lung transplantation, Malignancy, Sirolimus (SLR)

Session Information

Date: Monday, June 3, 2019

Session Name: Poster Session C: Lung: All Topics

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Hall C & D

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*Purpose: The use of mammalian target of rapamycin inhibitors (mTORi) in cardiothoracic transplantation has significantly increased over the past decade. Several recent clinical trials have demonstrated mTORi efficacy in combination with reduced cyclosporine dosing in heart transplant recipients. Considerably less evidence is available in lung transplant populations and is limited to small retrospective studies. The purpose of this study is to analyze clinical outcomes of using mTORi in combination with reduced dose of calcineurin inhibitors (CNI) in lung transplant recipients.

*Methods: Single center, retrospective, observational review including lung transplant recipients > 18 years of age under the care of UAB Lung Transplant between January 2000 and June 2018. Patients with history of multiple transplants or who received mTORi therapy < 3 months were excluded. Variables collected included patient demographics, immunosuppression (IS) regimens, indication for mTORi initiation, renal function tests, lung function tests, episodes of acute rejection, squamous cell carcinoma (SCC) episodes, CMV viremia, and mTORi tolerability. All patients received mTORi in combination with reduced dose of CNI.

*Results: Initial results include 25 patients, 15 males and 10 females with mean age of 59.5 years. We plan to obtain data on a total of 75 patients. Main indications for initiation of mTORi were preservation of renal function (48%), history of recurrent SCC (32%), and decline in lung function (16%). The majority of patients (92%) received immunosuppression regimens that included sirolimus, with median duration of mTORi therapy being 1.0 years. Sixty-eight percent of patients in the mTORi group either remain on therapy currently or expired before discontinuation. Episodes of acute rejection (n=2) and impaired wound healing (n=1) were the most common reasons for discontinuation of mTORi therapy. Patients’ outcomes are summarized in Table 1. Renal function after mTORi initiation remained stable. Three patients had episodes of acute rejection and six experienced progressive decline in FEV1 despite mTORi therapy. Two new episodes of SCC were reported.

*Conclusions: Addition of mTORi to reduced dose CNI in lung transplant recipients shows stabilization of renal dysfunction and decreasing incidence of SCC. Additional data analysis will help to identify the effect of mTORi on lung allograft function.

Table 1: Outcomes
Change in SCr (mg/dL) -0.06
Decrease in FEV1 >20%, no. 6
New Episodes of SCC, no. 2
Episodes of CMV Viremia, no. 1
Episodes of Acute Rejection, no. 3
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To cite this abstract in AMA style:

Frawley M, Leedy J, James A, Salter A, Rusanov V. Clinical Outcomes of Using mTOR Inhibitors with Reduced Dose of Calcineurin Inhibitors in Lung Transplant Recipients: A Single Center Experience [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/clinical-outcomes-of-using-mtor-inhibitors-with-reduced-dose-of-calcineurin-inhibitors-in-lung-transplant-recipients-a-single-center-experience/. Accessed March 1, 2021.

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