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

Cancer Immunol Immunother. 2017 Jan;66(1):45-50. doi: 10.1007/s00262-016-1918-2. Epub 2016 Oct 22.

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: Allotransplant; Antibody; Cancer; Immunotherapy; PD-1; Rejection.

Publication types

  • Case Reports

MeSH terms

  • Allografts
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / immunology
  • Graft Rejection / chemically induced*
  • Graft Rejection / immunology
  • Heart Transplantation / adverse effects*
  • Heart Transplantation / methods
  • Humans
  • Immunotherapy / adverse effects
  • Immunotherapy / methods
  • Male
  • Middle Aged
  • Neoplasms / immunology*
  • Nivolumab
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / immunology
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / immunology
  • Transplantation Immunology

Substances

  • Antibodies, Monoclonal
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab