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

Daan P. Hurkmans*, Jeroen G.H.P. Verhoeven, Kitty De Leur, Karin Boer, Arjen Joosse, Carla C. Baan, Jan H. Von Der Thüsen, Ron H.N. Van Schaik, Ron H.J. Mathijssen, Astrid A.M. Van Der Veldt, Dennis A. Hesselink

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

27 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Article number182
JournalJournal for ImmunoTherapy of Cancer
Volume7
Issue number1
DOIs
Publication statusPublished - 12 Jul 2019

Bibliographical note

Funding:
This research was partially funded by the Dutch Kidney Foundation. The
Dutch Kidney Foundation is a non-profit organization which subsidizes research and innovation in nephrology and renal transplantation care.

Publisher Copyright:
© 2019 The Author(s).

Research programs

  • EMC MM-03-86-08
  • EMC MM-04-39-05
  • EMC NIHES-03-30-01
  • EMC NIHES-03-30-02

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