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 (SIR+TAC+MMF/AZA) after BOS onset, using multivariable adjusted Cox regression and Inverse Probability of Treatment Weighting (IPTW)-adjusted Kaplan-Meier estimates. RESULTS: SIR+TAC+MMF/AZA (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/AZA, 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% of predicted at BOS documentation), SIR+TAC+MMF/AZA (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.