Immunomodulatory treatment of immune checkpoint inhibitor-induced myocarditis: Pathway toward precision-based therapy

Cardiovasc Pathol. 2020 Jul-Aug:47:107211. doi: 10.1016/j.carpath.2020.107211. Epub 2020 Feb 14.


Immune checkpoint inhibitor (ICI)-induced myocarditis carries a poor prognosis and is not fully understood. Similar to lymphocytic myocarditis and acute cellular rejection in heart transplant, ICI-induced myocarditis requires immune suppressive strategies. We aimed to describe ICI-induced myocarditis by presenting findings of comprehensive cardiovascular evaluations and outcomes of patients following a therapeutic approach similar to autoimmune disorders or allograft transplant rejection, and to discuss the molecular basis of the benefits of immune modulation and statins in ICI-myocarditis. Three patients with ICI-induced myocarditis (2 with positive biopsies and 1 based on cardiac magnetic resonance imaging with negative biopsy) underwent a complete cardiovascular workup, including cardiac catheterization with endomyocardial biopsy. Treatment was with intravenous immunoglobulins (IVIG) and statins in all cases, with additional colchicine (2 cases) or hydroxychloroquine (1 case). Immunohistochemical analysis demonstrated varied subsets of T cells involved in the inflammatory response. Therapy with IVIG and statins led to symptom resolution and cardiac function normalization at 1-month follow-up in all patients. Cancer therapy was resumed in all patients. One patient expired 10 months after the myocarditis episode due to advanced malignancy; two patients were alive, free of heart failure symptoms and cancer progression, at 1-year follow-up, and 1 patient was rechallenged with ICI. We suggest that treatment with IVIG and statins may allow for a prompt resumption of anti-cancer therapy (including ICI) and improve outcomes.

Keywords: Cardio-oncology; Immune checkpoint inhibitors; Immune-related adverse events; Immunotherapy; Myocarditis.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antineoplastic Agents, Immunological / adverse effects*
  • Cardiotoxicity
  • Colchicine / therapeutic use
  • Female
  • Humans
  • Hydroxychloroquine / therapeutic use
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Immunoglobulins, Intravenous / therapeutic use
  • Immunologic Factors / therapeutic use*
  • Ipilimumab / adverse effects*
  • Male
  • Melanoma / drug therapy*
  • Melanoma / immunology
  • Melanoma / secondary
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / immunology
  • Myelodysplastic Syndromes / pathology
  • Myocarditis / chemically induced
  • Myocarditis / drug therapy*
  • Myocarditis / immunology
  • Myocarditis / pathology
  • Nivolumab / adverse effects*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology
  • Treatment Outcome


  • Antineoplastic Agents, Immunological
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Immunoglobulins, Intravenous
  • Immunologic Factors
  • Ipilimumab
  • Nivolumab
  • Hydroxychloroquine
  • Colchicine