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

## TL;DR

Using sirolimus plus tacrolimus as immunosuppression improves survival in lung transplant patients with bronchiolitis obliterans syndrome, especially in severe cases.

## Contribution

This study demonstrates that sirolimus-based immunosuppression improves survival in BOS patients, particularly in those with severe disease.

## Key findings

- SIR+TAC and SIR+TAC+MMF/AZA were associated with better survival than MMF+TAC in BOS patients.
- Severely affected BOS patients had greater survival benefits with SIR+TAC+MMF/AZA and SIR+TAC combinations.
- Adding MMF or azathioprine to SIR+TAC may further improve short-term survival.

## Abstract

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.

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.

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 FEV1 decrease ≥30%/year, or FEV1<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%.

Sirolimus + tacrolimus immunosuppression may improve survival in BOS patients, especially severely affected patients with BOS Grade 3, or rapidly declining or low FEV1. Adding MMF or azathioprine to this combination may further increase short-term survival.