A Fatal Case of Myocarditis Following Myositis Induced by Pembrolizumab Treatment for Metastatic Upper Urinary Tract Urothelial Carcinoma

Int Heart J. 2020 Sep 29;61(5):1070-1074. doi: 10.1536/ihj.20-162. Epub 2020 Sep 12.

Abstract

We report a case of lethal myocarditis and myositis after pembrolizumab treatment for advanced upper urinary tract urothelial carcinoma. A 69-year-old man underwent pembrolizumab therapy as a second-line treatment. He had myalgia and a slightly elevated creatinine kinase (CK) on the day of the second administration of pembrolizumab. Five days later, the patient was admitted with severe fatigue and an abnormal gait. Physical examination revealed reduced muscle reflexes and proximal muscle weakness. An electrocardiogram (ECG) demonstrated a wide QRS complex ventricular rhythm. A marked elevation of cardiac enzymes, including CK, myoglobin, and cardiac troponin I, was detected. Myocardial biopsy revealed inflammatory cell infiltration and the partial impairment of myocardial tissue. The electromyogram was normal, but inflammation in myofibers was noted in a muscle biopsy. Myocarditis and myositis as immune-related adverse events (irAEs) were suspected, and the patient began intravenous steroid therapy and plasma exchange. However, the patient underwent cardiac arrest three days after admission and began extracorporeal membrane oxygenation and intra-aortic balloon pumping therapy. Despite steroid pulse therapy, the patient demonstrated no sign of improvement and subsequently died 17 days after admission. Immune-mediated myocarditis is a rare but fatal irAE of an immune checkpoint inhibitor (ICI). The present case suggests that myositis precedes myocarditis. Therefore, if myositis is suspected, subsequent myocarditis may need attention. In conclusion, we found that myositis and myocarditis developed in a patient with advanced urothelial carcinoma after pembrolizumab treatment. A routine follow-up of CK and cardiac troponin I, as well as an ECG, should be performed to identify any possible ICI-induced myocarditis and myositis quickly.

Keywords: Cardiac troponin I; Creatinine kinase; Immune checkpoint inhibitor; Immune-related adverse event; Myocardial biopsy; Steroid pulse therapy.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antineoplastic Agents, Immunological / adverse effects*
  • Carcinoma, Transitional Cell / drug therapy*
  • Carcinoma, Transitional Cell / secondary
  • Creatine Kinase / blood
  • Creatine Kinase, MB Form / blood
  • Echocardiography
  • Electromyography
  • Extracorporeal Membrane Oxygenation
  • Fatal Outcome
  • Glucocorticoids / therapeutic use
  • Heart Arrest
  • Humans
  • Intra-Aortic Balloon Pumping
  • Kidney Neoplasms / pathology*
  • Kidney Pelvis
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / secondary
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / secondary
  • Male
  • Muscle, Skeletal / pathology
  • Myocarditis / blood
  • Myocarditis / chemically induced*
  • Myocarditis / diagnostic imaging
  • Myocarditis / pathology
  • Myocardium / pathology
  • Myoglobin / blood
  • Myositis / blood
  • Myositis / chemically induced*
  • Myositis / pathology
  • Myositis / physiopathology
  • Plasma Exchange
  • Troponin I / blood

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • Glucocorticoids
  • Myoglobin
  • TNNI3 protein, human
  • Troponin I
  • pembrolizumab
  • Creatine Kinase
  • Creatine Kinase, MB Form