RT Journal Article SR Electronic T1 Donor-derived cell-free DNA detects kidney transplant rejection during nivolumab treatment JF Journal for ImmunoTherapy of Cancer JO J Immunother Cancer FD BMJ Publishing Group Ltd SP 182 DO 10.1186/s40425-019-0653-6 VO 7 IS 1 A1 Daan P. Hurkmans A1 Jeroen G. H. P. Verhoeven A1 Kitty de Leur A1 Karin Boer A1 Arjen Joosse A1 Carla C. Baan A1 Jan H. von der Thüsen A1 Ron H. N. van Schaik A1 Ron H. J. Mathijssen A1 Astrid A. M. van der Veldt A1 Dennis A. Hesselink YR 2019 UL http://jitc.bmj.com/content/7/1/182.abstract 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