Utility of Serial Donor-derived Cell-free DNA Measurements for Detecting Allograft Rejection in a Kidney Transplant Recipient After PD-1 Checkpoint Inhibitor Administration

Background. Donor-derived cell-free DNA (dd-cfDNA) is a useful biomarker of rejection that originates from allograft cells undergoing injury. Plasma levels <1% in kidney transplant recipients have a high negative predictive value for active allograft rejection. The utility of this biomarker in kidney transplant recipients receiving immune checkpoint inhibitor therapy is unknown. Methods. We describe a case in which serial dd-cfDNA monitoring facilitated the use of immune checkpoint inhibitor therapy, which is known to be associated with high rates of rejection, in a kidney transplant recipient with metastatic cancer. Results. A 72-y-old man with end-stage kidney disease secondary to autosomal dominant polycystic kidney disease underwent living unrelated kidney transplant in December 2010. His immunosuppression regimen included tacrolimus, mycophenolate, and prednisone. In July 2017, he presented with metastatic cutaneous squamous cell carcinoma. After his disease progressed through radiation therapy and cetuximab, he received pembrolizumab (antiprogrammed cell death protein 1). His dd-cfDNA level was undetectable at baseline, then increased during treatment but remained <1%. This trend, despite fluctuations in serum creatinine levels during therapy, allowed for continuation of pembrolizumab and successful treatment of his metastatic cancer without clinically evident allograft rejection. After discontinuation of pembrolizumab, dd-cfDNA levels fell below the level of detection. Genetic analysis of the cutaneous squamous cell carcinoma demonstrated a genetic profile distinct from the dd-cfDNA, indicating that tumor lysis did not impact increases in dd-cfDNA. Conclusions. Serial dd-cfDNA measurements may provide a useful, noninvasive biomarker for detecting allograft injury that may facilitate the use of immunomodulatory therapies in organ transplant recipients with cancer.