Acute fatal myocarditis after a single dose of anti-PD-1 immunotherapy, autopsy findings: a case report

Cardiovasc Pathol. 2020 May-Jun:46:107202. doi: 10.1016/j.carpath.2020.107202. Epub 2020 Jan 15.

Abstract

Nivolumab (PD-1 inhibitor) and Ipilimumab (CTLA-34 inhibitor) are both commonly used immune checkpoint inhibitor therapies for various cancers. Various adverse events are associated with these therapies, including hepatitis, nephritis, dermatitis, and myocarditis. It is believed these adverse events occur in part because modified cellular receptors lead to enhanced CD4 and CD8 lymphoproliferation. These events usually occur after several months and rounds of treatment. Here we present a case of an 81-year-old male with recurrent renal cell carcinoma (RCC) who experienced myocarditis after only a single dose of combination therapy with Nivolumab and Ipilimumab. He presented with elevated troponins and a third-degree heart block; three days after admission he died. Histologic examination revealed a predominance of CD3 T cells (CD4 > CD8) and CD68 macrophages, with occasional CD20 B cells. C4d staining was negative in the interstitial capillaries, suggesting that antibody-mediated injury of endothelial cells did not play a significant role in the pathogenesis of this myocarditis. Additional studies ruled out an infectious etiology. Immune checkpoint inhibitors are increasingly more common, and it is important clinicians are aware patients can present with myocarditis early in the course of treatment.

Keywords: Autopsy; Myocarditis; PD-1 immunotherapy.

Publication types

  • Case Reports

MeSH terms

  • Acute Disease
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / secondary
  • Fatal Outcome
  • Humans
  • Ipilimumab / administration & dosage
  • Ipilimumab / adverse effects*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / pathology
  • Male
  • Myocarditis / chemically induced*
  • Myocarditis / immunology
  • Myocarditis / pathology
  • Myocardium / immunology
  • Myocardium / pathology
  • Nivolumab / administration & dosage
  • Nivolumab / adverse effects*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*

Substances

  • Antineoplastic Agents, Immunological
  • Ipilimumab
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab