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Analysis of Corticosteroids in Immune Checkpoint Inhibitors (ICI) Induced Myocarditis- A Systematic Review of 352 Screened Articles

Author(s): Mona Sheikh, Saumil Patel, Shavy Nagpal, Zeynep Yukselen, Samina Zahid, Vivek Jha, Diana F Sánchez-Velazco, Sima Marzban, Odalys Frontela

Introduction
Immune Checkpoint Inhibitors (ICI) are used as a single agent or as a combination therapies for early or late-stage malignancies. The common malignancies that ICI targets include the following: melanoma, lung cancer, renal cell carcinoma, and hematological malignancies such as Hodgkin’s lymphoma. ICI use is associated with many immune-related adverse events, and ICI-induced myocarditis is one of the rare and most severe AE with a high mortality rate. There are no consensus evidence-based treatment guideline; the expert recommendation is to use high-dose steroids. We aim in this review to assess the effectiveness of steroids in treating ICI-induced myocarditis.

Methods
We searched the following database Pubmed, Scopus, Cinahl, and Google Scholar, using the following keywords: ICI-induced myocarditis, treatment, steroid. We included articles in the English language, case reports, case series, and published in the last five years.

Results
352 articles were screened using PRISMA guidelines. After excluding the articles that were duplicate, irrelevant, and did not meet inclusion criteria, 35 articles with a total number of 50 patients were included. All patients treated with ICI either as a single or combination regimen. The onset of symptoms post initiation varied from one day to a year. 46 out of the 50 cases received high doses of Intravenous steroids as a loading dose followed by an oral or intravenous maintenance dose. Out of 50 patients 14 patients (28%) died but 34 (68%) patients survived, and 2 (4%) patients data were not available. The mean age of the patients was 66.31 ± 14.071 (range 23-88 years), 29 were male (58%), 21 were female (42%). Most of the cases were from the USA (42%), followed by Australia (20%), Japan (14%), Germany, France, and China (4%), Switzerland, Canada, and Spain (2%), and for (6%) cases. A total of 23 patients had cardiovascular comorbidities (46%), which were HTN (14 patients, 60.87%), hyperlipidemia (5 patients, 21.73%), and less than 1% of patients had myocardial ischemia, congestive heart failure, atrial fibrillation, and peripheral vascular disease. While 26 patients (52%) had normal basal cardiac status.

Conclusion
Our results showed that high doses of steroids were effective in controlling cardiac myocyte inflammation and mortality by 28%. Race was not included in the analysis as it was not reported. More in depth studies are needed to provide a broader representation of steroids in myocarditis.

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