Donor-derived cell-free DNA detects kidney transplant rejection during nivolumab treatment

• Published in: Journal for immunotherapy of cancer Vol. 7; no. 1; p. 182
• Main Authors: Hurkmans, Daan P, Verhoeven, Jeroen G H P, de Leur, Kitty, Boer, Karin, Joosse, Arjen, Baan, Carla C, von der Thüsen, Jan H, van Schaik, Ron H N, Mathijssen, Ron H J, van der Veldt, Astrid A M, Hesselink, Dennis A
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 12.07.2019; BMJ Publishing Group LTD; BioMed Central; BMJ Publishing Group
• Subjects: Aged; Allograft rejection; Anti-PD-1; Antibodies; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; B cells; Biomarkers; Biopsy; Cancer; Cancer treatment; Case Report; Cell-Free Nucleic Acids; Creatinine; Cytokines; Cytotoxicity; Dd-cfDNA; DNA; Donor-derived cell-free DNA; Dosage and administration; Drug therapy; Edema; Female; Graft rejection; Graft Rejection - diagnosis; Graft Rejection - etiology; Health aspects; Hemodialysis; Humans; Immune checkpoint inhibition; Immunohistochemistry; Immunotherapy; Kidney transplantation; Kidney Transplantation - adverse effects; Kidney transplants; Lymphatic Metastasis; Lymphatic system; Lymphocytes; Lymphocytes - drug effects; Lymphocytes - immunology; Lymphocytes - metabolism; Medical research; Melanoma; Melanoma - complications; Melanoma - diagnosis; Melanoma - drug therapy; Metastasis; Monoclonal antibodies; Neoplasm Staging; Nivolumab; Nivolumab - adverse effects; Nivolumab - therapeutic use; Organ transplant recipients; Organ transplantation; Positron Emission Tomography Computed Tomography; Prescription writing; T cells; Targeted cancer therapy; Tissue Donors; Toxicity; Women; Donor-derived cell-free DNA; Immune checkpoint inhibition; Anti-PD-1; Immunotherapy; Nivolumab; Melanoma; Allograft rejection; Solid organ transplantation; Dd-cfDNA; Kidney transplantation
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1186/s40425-019-0653-6

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. 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. 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.