Background: In solid organ transplant (SOT) recipients, transplant rejection during immune checkpoint inhibitor (ICI) treatment for cancer is a clinical problem. Donor-derived cell-free DNA (dd-cfDNA) can be detected in blood and is a sensitive biomarker for diagnosis of acute rejection in SOT recipients. To our best knowledge, this is the first case report of a kidney transplant recipient with advanced cancer treated with ICI who was monitored with dd-cfDNA. Case presentation: A 72-year old female with a long-standing renal transplant was diagnosed with advanced melanoma in 2018 and was treated with the anti-PD1 antibody nivolumab. Within 12 days after the first administration of nivolumab, dd-cfDNA ratio increased to 23%, suggesting allograft rejection. Her kidney transplant function deteriorated and acute rejection was confirmed by renal transplant biopsy. As the rejection could not be controlled despite immunosuppressive treatment, a transplant nephrectomy was necessary and haemodialysis was started. Immunological analysis of the renal explant showed infiltration of alloreactive, nivolumab-saturated, PD1+ cytotoxic T cells. After transplant nephrectomy, she experienced nivolumab-related toxicity and rapid disease progression. Conclusion: Clinicians prescribing ICIs should be aware that SOT recipients are at risk of transplant rejection as a result of T cell activation. Dd-cfDNA is a sensitive biomarker and should be further studied for early detection of transplant rejection. Immunological analysis of the kidney explant showed marked graft infiltration with alloreactive PD-1+ cytotoxic T cells that were saturated with nivolumab.

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Keywords Allograft rejection, Anti-PD-1, Dd-cfDNA, Donor-derived cell-free DNA, Immune checkpoint inhibition, Immunotherapy, Kidney transplantation, Melanoma, Nivolumab, Solid organ transplantation
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Journal Journal for ImmunoTherapy of Cancer
Hurkmans, D.P. (Daan P.), Verhoeven, J.G.H.P. (Jeroen G. H. P.), de Leur, K, Boer, K, Joosse, A, Baan, C.C, … Hesselink, D.A. (2019). Donor-derived cell-free DNA detects kidney transplant rejection during nivolumab treatment. Journal for ImmunoTherapy of Cancer, 7(1). doi:10.1186/s40425-019-0653-6