Steroid-Refractory Myocarditis Induced by Immune Checkpoint Inhibitor Responded to Infliximab: Report of Two Cases and Literature Review

Cardiovasc Toxicol. 2024 Nov;24(11):1174-1191. doi: 10.1007/s12012-024-09918-6. Epub 2024 Sep 10.

Abstract

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death protein 1 and its ligand (PD-1/PD-L1) as well as anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4), have been widely used for treating solid tumors. Myocarditis is a potentially lethal immune-related adverse events (irAEs) caused by ICIs therapy. The treatment of steroid-refractory myocarditis is challenging. We reported two non-small-cell lung cancer patients with steroid-refractory myocarditis induced by ICI. The symptoms were not resolved after pulse corticosteroid therapy and subsequent treatment including intravenous immunoglobulin and mycophenolate mofetil. Considering the level of serum interleukin (IL)-6 decreased by > 50% and level of serum tumor necrosis factor-α (TNF-α) increased during the course of the disease, infliximab was used. Myocarditis gradually alleviated after infliximab treatment. The cases revealed that specific cytokine inhibitors have promising roles in the treatment of steroid-refractory myocarditis. Infliximab could be considered for patients with low level of IL-6 and elevated level of TNF-α.

Keywords: Cytokine inhibitors; Immune checkpoint inhibitors; Infliximab; Steroid-refractory myocarditis; Tocilizumab.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Drug Resistance
  • Humans
  • Immune Checkpoint Inhibitors* / adverse effects
  • Infliximab* / therapeutic use
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / blood
  • Lung Neoplasms* / drug therapy
  • Myocarditis* / chemically induced
  • Myocarditis* / diagnosis
  • Myocarditis* / drug therapy
  • Myocarditis* / immunology
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / blood

Substances

  • IL6 protein, human
  • Immune Checkpoint Inhibitors
  • Infliximab
  • Interleukin-6
  • Tumor Necrosis Factor-alpha