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Sirolimus Plus Tacrolimus Immunosuppression, with or without Mycophenolate Mofetil, May Improve Survival after Bronchiolitis Obliterans Syndrome in Lung Transplant Patients

M. Wijesinha, M. Terrin, B. Griffith, A. Iacono

University of Maryland School of Medicine, Baltimore, MD

Meeting: 2020 American Transplant Congress

Abstract number: 188

Keywords: Immunosuppression, Lung transplantation, Rejection, Survival

Session Information

Date: Saturday, May 30, 2020

Session Name: Living in the Real World: Decision Making and Outcomes After Lung Transplant

Session Time: 3:15pm-4:45pm

 Presentation Time: 3:39pm-3:51pm

Location: Virtual

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*Purpose: There are very few ways to improve survival after bronchiolitis obliterans syndrome (BOS), the leading cause of death in lung transplant patients. Two long-term studies have found that prophylactic sirolimus + tacrolimus immunosuppression early after lung transplantation is associated with significantly improved survival and lower BOS risk compared to the traditional mycophenolate mofetil (MMF) + tacrolimus regimen, but among patients with BOS, data comparing survival between regimens are lacking.

*Methods: This study included lung transplant patients with BOS in the U.S. Scientific Registry for Transplant Recipients (SRTR), transplanted from May 2005-August 2016 and initially receiving traditional maintenance immunosuppression (tacrolimus/cyclosporine + MMF/azathioprine) and induction with basiliximab, daclizumab, antithymocyte globulin, alemtuzumab, or no induction. Patients missing data on BOS grade (1-3) or immunosuppression following BOS diagnosis were excluded. Survival was compared between BOS patients receiving tacrolimus + sirolimus [TS], tacrolimus + sirolimus + antimetabolite (MMF/azathioprine) [TSA], or tacrolimus + MMF [TM], based on Kaplan-Meier estimates and Cox regression adjusting for demographic and clinical factors, including transplant center-specific survival among BOS patients.

*Results: Combining BOS grades 1-3 without adjustment, 1-year survival and median [interquartile range] survival times by treatment group were, TSA: 100%, 4.5 [2.9-6.5] years, n=14; TS: 81%, 4.4 [1.6- -] years, n=37; TM: 78%, 3.5 [1.3-7.0] years, n=471. The groups had different distributions of BOS grades (p=0.004); prevalence of Grade 3 BOS at baseline was 36% in TSA, 51% in TS, and 27% in TM. Each group had patients from over 10 different centers. In adjusted analysis, TSA (HR=0.44, p=0.05) and TS (HR=0.55, p=0.03) were associated with better survival than TM. Effect sizes were larger when restricting to BOS Grade 3 patients; TSA again showed a trend towards the most favorable survival (HR=0.21, p=0.17) and TS (HR=0.35, p=0.04) also showed better survival, compared to TM.

*Conclusions: Maintenance immunosuppression combining sirolimus and tacrolimus may significantly improve survival in patients with BOS (especially Grade 3). Adding MMF or azathioprine to this combination appears promising, particularly for short-term survival in these patients with a high mortality rate, while being attentive to risks of possible over-immunosuppression with this strategy combining all 3 drug classes.

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To cite this abstract in AMA style:

Wijesinha M, Terrin M, Griffith B, Iacono A. Sirolimus Plus Tacrolimus Immunosuppression, with or without Mycophenolate Mofetil, May Improve Survival after Bronchiolitis Obliterans Syndrome in Lung Transplant Patients [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/sirolimus-plus-tacrolimus-immunosuppression-with-or-without-mycophenolate-mofetil-may-improve-survival-after-bronchiolitis-obliterans-syndrome-in-lung-transplant-patients/. Accessed March 1, 2021.

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