Donor-derived cell-free DNA detects kidney transplant rejection during nivolumab treatment. Issue 1 (12th July 2019)

• Record Type: Journal Article
• 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.
• Is Part Of: Journal for immunotherapy of cancer. Volume 7:Issue 1(2019)
• Publication Date: 2019-07-12
• Subjects: Allograft rejection -- Anti-PD-1 -- Dd-cfDNA -- Melanoma -- Donor-derived cell-free DNA -- Immune checkpoint inhibition -- Immunotherapy -- Nivolumab -- Solid organ transplantation -- Kidney transplantation; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1186/s40425-019-0653-6
• Languages: English
• ISSNs: 2051-1426

Abstract

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.