232.4: Donor-derived Cell-free DNA (Dd-cfDNA) for Assessment of Response After Treatment of Allograft Rejection

Introduction: Surveillance of dd-cfDNA after therapy for rejection represents a promising strategy for monitoring post-treatment response. We assessed post-rejection kinetics of dd-cfDNA among kidney transplant recipients in the Kidney allograft Outcomes AlloSure Registry (KOAR, NCT03326076). Methods: We identified patients with biopsy-proven allograft rejection (BPAR), defined as ABMR, TCMR, or Mixed (Banff 2019), biopsy-paired dd-cfDNA measurements (within ≤30d of biopsy), and follow-up results 60-150 days after BPAR. When available, treatment and follow-up histology data was also analyzed. Results: 48 episodes of BPAR (24 TCMR, 19 ABMR, 5 Mixed) and paired dd-cfDNA results were identified in 42 patients (Table 1). Overall, a significant reduction was seen between the median index (1.36%, IQR: 0.29-2.25) and follow-up dd-cfDNA results (0.35%, IQR: 0.13-0.95; p < 0.01) (Figure 1a). For patients with concurrent eGFR measurements, no statistically significant improvement was seen. These patterns held when analysis was limited to TCMR andABMR/Mixed rejections (Figure 1b, 1c). 7 patients (2 ABMR, 4 TCMR, and 1 Mixed; median index dd-cfDNA 1.15%, IQR: 0.31-2.46) had repeat biopsies within 30days of their follow-up testing; 1 patient with acute ABMR had chronic active ABMR on repeat biopsy, with a dd-cfDNA of 1.86%, while the remainder had eitherno rejection or borderline findings (median dd-cfDNA 0.74%, IQR: 0.30-2.59). Conclusions: Our findings highlight that reduction in dd-cfDNA is commonly seen following BPAR, suggesting that most patients experience a “molecularresponse” to therapy. Studies are needed to better understand the prognostic significance of a molecular response and how persistent elevations in dd-cfDNAafter treatment should guide subsequent management.