Racial Differences in Immunosuppression and Lung Transplant Outcomes

Purpose Maintenance of immunosuppression in lung transplant recipients (LTx) is integral for preventing allograft rejection, with tacrolimus as a mainstay drug. Prior research from our group showed significantly poorer outcomes for Non-European Ancestry patients (Non-EA) as compared to those of European Ancestry (EA) and that donor-derived cell-free DNA (ddcfDNA) predicts molecular allograft injury in LTx. This study examines differences in immunosuppression between EA and Non-EA LTx in the context of disparate outcomes. Methods 453 LTx within two multicenter cohorts were analyzed based on self-identified race. Serial post-transplant tacrolimus blood levels and dosages were collected. Tacrolimus trough levels were dichotomized as “therapeutic” or “non-therapeutic” based on goal trough level ranges and were analyzed over 6-month periods up to 18 months post-transplant. Serial plasma samples were assayed for %ddcfDNA by shotgun sequencing and log-transformed to adjust for skewness. Results The study cohort was 80.1% EA and 19.9% Non-EA. The odds and mean number of therapeutic trough levels were similar between EA and Non-EA within the 0-6 (OR=0.98 95% CI 0.71 - 1.35, p=0.91), 6-12 (OR=2.25 95% CI 0.93 - 5.45, p=0.07), and 12-18-month (OR= 1.41 95% CI 0.73 - 2.71, p=0.31) intervals. However, non-EA patients required twofold higher median tacrolimus dosages to reach therapeutic trough levels as compared to EA patients (Fig. 1a). Furthermore, non-EA patients had significantly higher ddcfDNA levels as compared to non-EA (Fig. 1b). Conclusion Despite disparities in post-transplant outcomes, non-EA achieve similar therapeutic levels of tacrolimus as compared to EA but require significantly higher doses to do so. At a molecular level, non-EA showed significantly higher levels of molecular allograft injury as assessed by ddcfDNA despite equivalent immunosuppression trough levels. Further research is needed to investigate racial outcome disparities and use of ddcfDNA to augment immunosuppressive monitoring in minority LTx.