Fatal Myocarditis Following Treatment with the PD-1 Inhibitor Nivolumab

J Forensic Sci. 2018 May;63(3):954-957. doi: 10.1111/1556-4029.13633. Epub 2017 Aug 17.

Abstract

Therapeutic antibodies targeting the programmed cell death protein 1 (PD-1) pathway function as immune checkpoint inhibitors, allowing the immune system to recognize tumors which otherwise escape immune surveillance. However, these agents can also elicit an autoimmune response by inhibiting the ability of non-neoplastic tissues and regulatory cells to suppress the immune system. Here we present a fatal case of active myocarditis in a 55-year-old man with non-small-cell lung cancer which occurred following monotherapy with the PD-1 inhibitor nivolumab (Opdivo). He presented with acute right-sided heart failure and died 1 day after admission. Postmortem examination revealed multiple gelatinous lesions in the myocardium of the interventricular septum and the bilateral atria and ventricles which had microscopic features diagnostic of myocarditis. Subsequent studies failed to identify an infectious cause. Immune checkpoint inhibitors are an increasingly common addition to anticancer regimens and they should be considered in the evaluation of acute myocarditis.

Keywords: autopsy; drug effects; forensic science; immunotherapy/adverse effects; myocarditis/immunology; myocarditis/pathology; nivolumab; programmed cell death 1 receptor.

Publication types

  • Case Reports

MeSH terms

  • Antibodies, Monoclonal / adverse effects*
  • Antineoplastic Agents / adverse effects*
  • Autoimmune Diseases / chemically induced*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Fatal Outcome
  • Humans
  • Lung Neoplasms / drug therapy
  • Male
  • Middle Aged
  • Myocarditis / chemically induced*
  • Myocarditis / immunology
  • Nivolumab

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Nivolumab