To Treat or Not to Treat: DSA Positive Lung Transplant Recipients

Purpose Donor-specific antibodies (DSA) is a major risk factor for chronic lung allograft dysfunction (CLAD) after lung transplantation (LTx). Unfortunately, DSA management (Rx) varies significantly. To date, there is no accepted standard on when to initiate treatment. This study examines whether the timing of DSA treatment alters outcomes. Methods 435 LTx subjects enrolled in two cohort studies were included. They underwent surveillance and clinically-indicated HLA DSA testing. DSA+patients were treated with a Rituximab or Bortezomib-based regimen either before they showed any clinical or histological signs of AMR (Early Rx) or when they developed these signs of AMR (Late Rx); choice was based on provider's practice. Outcomes: Time from transplant to CLAD-free survival, defined as being alive and CLAD-free. CLAD was adjudicated by a committee. Measure: Allograft injury at time of Rx was quantified via plasma donor-derived cell-free DNA (ddcfDNA), a validated biomarker. Analyses: Baseline characteristics, allograft injury, DSA clearance and CLAD-free survival were compared between treatment groups and controls (DSA- patients). Results Median follow-up was 10 (IQR = 11 - 37) months. 58% of patients developed HLA DSA, which was predominantly Class II than class I (85% vs. 15%). DSA+patients were treated either early (n = 49) or Late (n = 97). The remaining 32% of DSA+patients lacked relevant clinical data or were not treated. Baseline characteristics and DSA specificities were similar between treatment groups. However, Late AMR showed higher median %ddcfDNA (4% vs 1%, p Conclusion This study supports Early Rx of DSA over Late Rx since Early Rx shows improved CLAD-free survival. Multivariate analyses to identify other potential covariates are being planned.