The Results of the PRISM (Prediction of Rejection In Sensitized patient blood saMples) Trial with a Novel Bioassay

Abstract

Background kSORT, a 17 gene blood biomarker, has been retrospectively validated for detection of BPAR and immune quiescence in kidney tx. This is the first assessment of the predictive accuracy of pre and serial post-tx kSORT in a prospective clinical trial of high immunologic risk tx patients. Methods 113 kidney tx recipients, with cPRA of >50% (median 97%) were enrolled pre-tx and followed for 6 mo post-tx in the PRISM (Prediction of Rejection In Sensitized SaMples) trial. A protocol bx was done at 6 mo and/or at graft dysfunction. kSORT was run pre-tx and 5 times post-tx (0.5, 1, 2, 3, 6 mo). Customized software kSAS generated actionable immune risk scores as High-(HR) or Low-(LR) risk for AR. All patients had induction with Thymoglobulin and maintained on TAC, MMF and prednisone. Statistical analysis used R and Fisher's exact test. Results 98 evaluable patients had kSORT analyzed across 560 blood samples and results correlated with 93 bx (34 for cause), with 12 AR and 20 borderline (BL)-AR. 15.7% of kSORT had a null call of Indeterminate-Risk (IR). The overall predictive accuracy of the pre-tx kSORT (assessed in 54 pts) was 90.3% for no-rejection post-tx. For pre-tx kSORT: 80% wereLR,18% were -HR and did not correlate with cause of sensitization. For post-tx blood samples paired with bx, 51 patients had no-rejection and 47 were correctly classified as LR (specificity 92.2%). Among the 20 BL-AR, kSORT was HR in 93% with definitive kSORT scores (HR in 14; LR in 1, IR in 5). Among the 12 AR, 78% were HR. Combining the AR and BL-AR group as “rejection”, the accuracy of kSORT for matching the same results as the biopsy was 84%. A diagnostic odds ratio of a kSORT+ (HR) call in the AR and BL-AR group, compared to the odds of a LR call in the same group was >27-fold (dOR=27.4), confirming that the kSORT test can discriminate between BPAR outcomes (p<0.0001). After treatment of AR, 42% remained kSORT positive. Conclusions kSORT can be applied both pre-tx and at serial times post-tx to monitor patients at low and high risk of rejection in highly sensitized patients. A LR kSORT score has 90% accuracy for predicting freedom from rejection, either before or after tx. Pre and post-tx kSORT assessment is an important adjunct measure for instituting Precision Medicine in the management of sensitized renal tx recipients and optimizing their outcomes.