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Abstract: SA-PO1142

Utility of Donor-Derived Cell-Free DNA for Detecting Allograft Rejection with PD-L1 Checkpoint Inhibitor Use

Session Information

Category: Trainee Case Report

  • 1902 Transplantation: Clinical

Authors

  • Lakhani, Laila, Johns Hopkins Hospital, Baltimore, Maryland, United States
  • Alasfar, Sami, Johns Hopkins Hospital, Baltimore, Maryland, United States
  • Bhalla, Anshul, Johns Hopkins Hospital, Baltimore, Maryland, United States
  • Aala, Amtul, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
  • Lipson, Evan J., Johns Hopkins University, Baltimore, Maryland, United States
  • Brennan, Daniel C., Johns Hopkins, Baltimore, Maryland, United States
Introduction

Donor derived cell free DNA (dd-cfDNA) is a useful biomarker that originates from allograft cells undergoing injury. Levels <1% have strongly correlated with absence of active rejection. We describe a case where serial dd-cfDNA monitoring allowed the use of immune checkpoint inhibitor therapy in a renal transplant recipient.

Case Description

A 72 year old man with ESRD from ADPKD underwent living unrelated kidney transplant in Dec 2010. His immunosuppression regimen included tacrolimus 2mg bid, mycophenolate 500mg bid and prednisone 5mg daily. In July 2017, he was diagnosed with metastatic squamous cell cancer. He underwent radiation therapy followed by chemotherapy with Cetuximab. However, in the setting of disease progression, PD-L1 inhibitor was considered. A baseline dd-cfDNA was 0.23%. PD-L1 inhibitor, Pembrolizumab, was initiated in Nov 2017 with serial dd-cfDNA monitoring (weekly x 8 weeks, followed by monthly). Despite serum creatinine fluctuations (Fig 1), the relative change in dd-cfDNA of <65% and overall <1% (Fig 2) reassured of a low likelihood of active rejection, allowing the continuation of therapy. Pembrolizumab was used for about 1 year; however, subsequent imaging was concerning for local disease progression and Pembrolizumab was discontinued in Nov 2018. Thereafter, his dd-cfDNA returned to baseline with excellent allograft function, suggesting that the initial elevation may have been from tumor death.

Discussion

Dd-cfDNA is a helpful noninvasive marker for diagnosing graft rejection with checkpoint inhibitor use. Future investigations into sequencing the dd-cfDNA will help determine whether it is of tumor vs allograft origin.

Fig 1

Fig 2