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

Laila Lakhani, MD; Sami Alasfar, MD; Anshul Bhalla, MD; Amtul Aala, MD; Avi Rosenberg, MD; Darin Ostrander, PhD; Megan D. Schollenberger, CRNP; Daniel C. Brennan, MD; Evan J. Lipson, MD

doi:10.1097/TXD.0000000000001113

Transplantation Direct (Feb 2021)

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

Laila Lakhani, MD,
Sami Alasfar, MD,
Anshul Bhalla, MD,
Amtul Aala, MD,
Avi Rosenberg, MD,
Darin Ostrander, PhD,
Megan D. Schollenberger, CRNP,
Daniel C. Brennan, MD,
Evan J. Lipson, MD

Affiliations

Laila Lakhani, MD: 1 Emory Transplant Center, Emory University School of Medicine, Atlanta, GA.
Sami Alasfar, MD: 2 Johns Hopkins Medical Institute, Baltimore, MD.
Anshul Bhalla, MD: 3 James D Eason Transplant Institute, Methodist University Hospital, University of Tennessee Health Science Center, Memphis, TN.
Amtul Aala, MD: 4 Beth Israel Deaconess Medical Center, Boston, MA.
Avi Rosenberg, MD: 2 Johns Hopkins Medical Institute, Baltimore, MD.
Darin Ostrander, PhD: 2 Johns Hopkins Medical Institute, Baltimore, MD.
Megan D. Schollenberger, CRNP: 5 Johns Hopkins Bloomberg~Kimmel Institute for Cancer Immunotherapy, Kimmel Cancer Center, Baltimore, MD.
Daniel C. Brennan, MD: 2 Johns Hopkins Medical Institute, Baltimore, MD.
Evan J. Lipson, MD: 5 Johns Hopkins Bloomberg~Kimmel Institute for Cancer Immunotherapy, Kimmel Cancer Center, Baltimore, MD.

DOI: https://doi.org/10.1097/TXD.0000000000001113
Journal volume & issue: Vol. 7, no. 2
p. e656

Abstract

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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.

Published in Transplantation Direct

ISSN: 2373-8731 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Surgery
Website: http://journals.lww.com/transplantationdirect/Pages/default.aspx

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