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

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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.

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Abbreviations

CAV:

Cardiac allograft vasculopathy

LAD:

Left anterior descending

EF:

Ejection fraction

irAE:

Immune-related adverse event

IRB:

Institutional review board

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Acknowledgements

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

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Authors and Affiliations

  1. Department of Hematology and Medical Oncology, Emory University School of Medicine, 1365-C Clifton Road, NE, Suite C3080, Atlanta, GA, 30322, USA

    Taofeek K. Owonikoko, Mukesh Kumar, Rathi N. Pillai & Suresh S. Ramalingam

  2. Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Taofeek K. Owonikoko, Gabriel L. Sica, Rafi Ahmed & Suresh S. Ramalingam

  3. Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA

    Shu Yang, Alice O. Kamphorst, Rama Akondy & Rafi Ahmed

  4. Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA

    Vivek Nautiyal, Monica S. Chatwal, Wendy M. Book & Anurag Sahu

  5. Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA

    Gabriel L. Sica

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  1. Taofeek K. Owonikoko
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  2. Mukesh Kumar
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  13. Suresh S. Ramalingam
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Corresponding author

Correspondence to Taofeek K. Owonikoko.

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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.

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

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Owonikoko, T.K., Kumar, M., Yang, S. et al. Cardiac allograft rejection as a complication of PD-1 checkpoint blockade for cancer immunotherapy: a case report. Cancer Immunol Immunother 66, 45–50 (2017). https://doi.org/10.1007/s00262-016-1918-2

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  • DOI: https://doi.org/10.1007/s00262-016-1918-2

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