Myocarditis associated with immune checkpoint inhibitors: Practical considerations in diagnosis and management

Abstract

Immune checkpoint inhibitors (ICI) have caused radical changes in the treatment scheme of many types of cancer in the past 10 years. ICIs are specific monoclonal antibodies that increase T-cell mediated immune response against cancer cells. Despite important advances in cancer treatment, uncontrolled activation of cytotoxic T cells has brought along many autoimmune clinical side effects, especially acute myocarditis. Although the incidence of ICI-related myocarditis is about 1%, it is remarkable in terms of mortality rate reaching 46% and demonstrating the necessity of rapid diagnosis and multidisciplinary approach. The present review aimed to summarize the heterogeneous symptomatology of ICI-associated myocarditis, clinical presentation ranging from elevated asymptomatic cardiac enzyme levels to cardiogenic shock, prominent diagnostic value of cardiac magnetic resonance imaging, and current information on the effectiveness of immunosuppressants in therapy.

Figure 1

Major types of immune checkpoint inhibitor-related cardiotoxicity CTLA-4 - cytotoxic T lymphocyte-associated antigen-4; PD-1 - programmed cell death protein receptor; PD-L-1 - programmed cell death protein ligand

Figure 2

How to make the differential diagnosis in patients using ICI and presenting nonspecific symptoms: An algorithm for the clinician BNP/NT-proBNP - brain natriutetic peptide; LV - left ventricle; EF - efection fraction; MRI - magnetic resonance imaging; CT - computed tomography; PET-CT - positron emission tomography-computed tomography; EMB - endomyocardial biopsy

Figure 3

Follow-up of the patient according to the response to corticosteroid treatment in ICI-related myocarditis ICI - immune checkpoint inhibitors; ECG - electrocardiogram; LVEF - left ventricular ejection fraction; IVIg - intravenous immunoglobulin; ATG - anti-thymocyte globulin *There are no prospective or randomized controlled studies evaluating treatment options for ICI-related myocarditis. The available information is based on case series experience. There is no clear information about the optimal duration and dose for corticosteroid therapy. However, based on the experience, it is recommended to continue the treatment for 4-6 weeks and to reduce it according to clinical and troponin levels. **The American Society of Clinical Oncology (ASCO) guidelines recommend the initial dose for corticosteroid therapy as 1 mg/kg/day oral or intravenous (IV). In case series in the literature, it is reported that faster recovery in clinical and troponin levels and lower rates of major adverse cardiovascular events (MACE) are observed during follow-up period with a high initial dose (1000 mg/day/IV 3-5 days) of corticosteroid treatment

Figure 4

Management of immune checkpoint inhibitor-related myocarditis-ASCO recommendations