Review: Treatment of immune checkpoint inhibitor-associated myocarditis

Abstract

Immune checkpoint inhibitors (ICIs) are a form immunotherapy where the negative regulators of host immunity are targeted, thereby leveraging the own immune system. ICIs have significantly improved cancer survival in several advanced malignancies and there are currently over 90 different cancer indications for ICIs. The majority of patients develop immune-related adverse events (irAEs) during ICI therapy. Most are mild but a small subset of patients will develop severe and potentially fatal irAEs. A serious cardiovascular complication of ICI therapy is myocarditis. While the incidence of myocarditis is low, mortality rates of up to 50% have been reported. The mainstay of ICI associated myocarditis treatment is high-dose corticosteroids. Unfortunately, half of patients with myocarditis do not show clinical improvement after corticosteroid treatment. Also, high doses of corticosteroids may adversely impact cancer outcomes. There is an evidence gap in the optimal second-line treatment strategy. Currently, there is a paradigm shift in second-line treatment taking place from empirical corticosteroid-only strategies to either intensified initial immunosuppression where corticosteroids are combined with another immunosuppressant or targeted therapies directed at the pathophysiology of ICI myocarditis. However, the available evidence to support these novel strategies is limited to observational studies and case reports. The aim of this review is to summarize the literature, guidelines, and future directions on the pharmacological treatment of ICI myocarditis.

Inflammation and Heart Diseases: Immunology, Cardiology,and Rheumatology,

“…Randomized clinical trials are few, and they have largely failed to show efficacy that is consistent across trials. Heemelaar et al 9 from Boston, MA, address a specific form of acute myocarditis associated with the use of immune checkpoint inhibitors. In these cases, treatments aimed at inducing an immune response to cancer cells occasionally result in autoimmune reactions to the myocardium, causing heart failure, shock, and life-threatening arrhythmias.…”