Requiring Caution in the Interpretation of Donor-Derived Cell-Free DNA Levels During Cancer Treatment in a Kidney...

Donor-derived cfDNA (dd-cfDNA) indicates allograft rejection when > 1% of total cfDNA, but tumor-derived cfDNA can interfere in cancer patients.

A 61-year-old male kidney transplant recipient with metastatic renal cell carcinoma (RCC) initiated avelumab and axitinib. Following two cycles of Immno-oncology (IO) therapy, serum creatinine (Cr) levels increased to 3.1 mg/dL. Although %dd-cfDNA remained below the conventional 1% threshold, it rose to 0.41%, representing a relative change value (RCV) of +178% from baseline. Two weeks later, Cr increased to 4.5 mg/dL, accompanied by severe hyponatremia, necessitating discontinuation of IO therapy, treated with methylprednisolone and resumed IO therapy; however, Cr remained elevated; he required hemodialysis.

RCV from baseline %dd-cfDNA may serve as a more reliable indicator of allograft injury, facilitating earlier intervention in transplant recipients undergoing IO therapy.