PT - JOURNAL ARTICLE AU - Daan P. Hurkmans AU - Jeroen G. H. P. Verhoeven AU - Kitty de Leur AU - Karin Boer AU - Arjen Joosse AU - Carla C. Baan AU - Jan H. von der Thüsen AU - Ron H. N. van Schaik AU - Ron H. J. Mathijssen AU - Astrid A. M. van der Veldt AU - Dennis A. Hesselink TI - Donor-derived cell-free DNA detects kidney transplant rejection during nivolumab treatment AID - 10.1186/s40425-019-0653-6 DP - 2019 Dec 01 TA - Journal for ImmunoTherapy of Cancer PG - 182 VI - 7 IP - 1 4099 - http://jitc.bmj.com/content/7/1/182.short 4100 - http://jitc.bmj.com/content/7/1/182.full SO - J Immunother Cancer2019 Dec 01; 7 AB - 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.Daan P. Hurkmans and Jeroen G.H.P. Verhoeven contributed equally as first authorsAstrid A.M. Van der Veldt and Dennis A. Hesselink contributed equally as senior authorsAbbreviations:dd-cfDNADonor-derived cell-free DNAGILGraft infiltrating lymphocyteICIImmune checkpoint inhibitorSOTSolid organ transplantation