Cancer Immunology, Immunotherapy

, Volume 66, Issue 1, pp 45–50 | Cite as

Cardiac allograft rejection as a complication of PD-1 checkpoint blockade for cancer immunotherapy: a case report

  • Taofeek K. Owonikoko
  • Mukesh Kumar
  • Shu Yang
  • Alice O. Kamphorst
  • Rathi N. Pillai
  • Rama Akondy
  • Vivek Nautiyal
  • Monica S. Chatwal
  • Wendy M. Book
  • Anurag Sahu
  • Gabriel L. Sica
  • Rafi Ahmed
  • Suresh S. Ramalingam
Original Article

Abstract

Introduction

The increased availability of immunotherapeutic agents for the treatment of a wide array of cancer in the general oncology practice setting will reveal rare and unique toxicities.

Materials and methods

The mechanism of cardiac allograft rejection in the context of PD-1 antibody therapy was explored in a patient with cutaneous squamous cell cancer complicating long-standing cardiac allograft. Immune cell infiltrate in the myocardium and peripheral blood lymphocyte repertoire were assessed using myocardial biopsy and temporal analysis of peripheral blood samples. The efficacy of high-intensity immunosuppression to reverse graft rejection was explored.

Results

Endomyocardial biopsy showed acute moderate diffuse cellular rejection with a predominant population of CD3+, CD8+ and CD4+ infiltrating lymphocytes; peripheral blood circulating lymphocytes showed a high frequency of proliferating and activated CD8+ T cells expressing PD-1 compared to a normal control. There was no difference in the activation and proliferation of CD4+ T cells compared to a normal control. Cardiac function improved following high-intensity immunosuppression and patient survived for up to 7 months after discontinuation of nivolumab.

Conclusions

Immune checkpoint inhibitors should be avoided in allograft recipients but high-intensity immunosuppression is effective to salvage allograft rejection induced by these agents.

Keywords

Cancer Immunotherapy Rejection Allotransplant PD-1 Antibody 

Abbreviations

CAV

Cardiac allograft vasculopathy

LAD

Left anterior descending

EF

Ejection fraction

irAE

Immune-related adverse event

IRB

Institutional review board

Notes

Acknowledgements

This work was supported in part by grant support from the US National Institute of Health Grant 1K23CA164015 (TK Owonikoko).

Compliance with ethical standards

Conflict of interest

T. K Owonikoko and S. S Ramalingam received research funding and served on advisory board for Astra Zeneca, Bristol-Myers Squib, Merck and Genentech. All other authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Taofeek K. Owonikoko
    • 1
    • 2
  • Mukesh Kumar
    • 1
  • Shu Yang
    • 3
  • Alice O. Kamphorst
    • 3
  • Rathi N. Pillai
    • 1
  • Rama Akondy
    • 3
  • Vivek Nautiyal
    • 4
  • Monica S. Chatwal
    • 4
  • Wendy M. Book
    • 4
  • Anurag Sahu
    • 4
  • Gabriel L. Sica
    • 2
    • 5
  • Rafi Ahmed
    • 2
    • 3
  • Suresh S. Ramalingam
    • 1
    • 2
  1. 1.Department of Hematology and Medical OncologyEmory University School of MedicineAtlantaUSA
  2. 2.Winship Cancer InstituteEmory UniversityAtlantaUSA
  3. 3.Department of Microbiology and Immunology, Emory Vaccine CenterEmory University School of MedicineAtlantaUSA
  4. 4.Department of MedicineEmory University School of MedicineAtlantaUSA
  5. 5.Department of PathologyEmory University School of MedicineAtlantaUSA

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