Work

Survival improvement with sirolimus plus tacrolimus immunosuppression for treatment of bronchiolitis obliterans syndrome after lung transplantation

Year: 2025

Type: article

Abstract: Background Chronic rejection, usually manifesting as bronchiolitis obliterans syndrome (BOS), is the leading cause of death among lung transplant patients. Prior lung transplant studies showed higher overall survival and lower BOS incidence associated with sirolimus (SIR) + tacrolimus (TAC) versus conventional mycophenolate mofetil (MMF) + TAC immunosuppression. However, after BOS occurs, it is unknown how immunosuppressive drugs may be linked to survival. Methods This study included U.S. lung transplant recipients in the Lung Allocation Score era (starting May 2005), with a BOS diagnosis documented from 2006 to 2020, in the Scientific Registry of Transplant Recipients dataset. Survival was compared between patients receiving MMF+TAC, SIR+TAC, or SIR+TAC+MMF/azathioprine after BOS onset, using multivariable adjusted Cox regression and Inverse Probability of Treatment Weighting (IPTW)-adjusted Kaplan-Meier estimates. Results SIR+TAC+MMF (HR=0.60, p=0.03, n=47) and SIR+TAC (HR=0.67, p=0.04, n=95) were associated with better survival than MMF+TAC (n=1012); each group contained patients from >15 centers. IPTW-adjusted survival probabilities for SIR+TAC+MMF, SIR+TAC, and MMF+TAC, respectively, were, 1-year: 91%, 84%, 80% and 5-year: 50%, 58%, 42%. Within severely affected BOS patients (BOS Grade 3, or FEV 1 decrease ≥30%/year, or FEV 1 <25% predicted at BOS documentation), SIR+TAC+MMF (HR=0.32, p=0.03) and SIR+TAC (HR=0.50, p=0.05) had larger survival advantages over MMF+TAC; the respective survival probabilities were, 1-year: 91%, 70%, 59%, and 5-year: 41%, 35%, 20%. Conclusions Sirolimus + tacrolimus immunosuppression may improve survival in BOS patients, especially severely affected patients with BOS Grade 3, or rapidly declining or low FEV 1 . Adding MMF or azathioprine to this combination may further increase short-term survival.

Source: JHLT Open

DOI: 10.1016/j.jhlto.2025.100469

Authors: Marniker Wijesinha, Michael Terrin, Si Pham, Aldo Iacono

Institutions: Northwell Health, North Shore University Hospital, University of Maryland, Baltimore

Language: English

Topic: Transplantation: Methods and Outcomes

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,500