Systematic review of immunotherapy-associated cardiotoxicities.

Abstract

e24005 Background: In recent years, the number of FDA-approved cancer immunotherapy treatments has increased exponentially, including immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T-cell therapies. Immunotherapy has revolutionized cancer treatment by enabling the immune system to target tumors and significantly increasing survivorship. It offers a powerful therapeutic option but has also been hypothesized to increase the incidence of immune-related adverse events. This review evaluates the correlation between immunotherapy oncological treatments and resulting cardiovascular adverse events (CAE) from immune-related cardiotoxicities. Methods: A systematic review was conducted using the 2022 European Society of Cardiology Guidelines on Cardio-Oncology. The 837 cited articles were used to construct a database. Then, two expert opinions, one from medical oncology and one from cardiology, were used to form a MeSH database of 355 terms, refined to 81 terms and 44 full-text articles. Two researchers conducted separate PubMed searches utilizing the list of MESH terms, which resulted in identifying 46 additional articles. All 90 abstracts were individually screened using the Covidence systematic review tool resulting in 47 full-text articles; 34 met eligibility criteria. The articles were analyzed using a standardized data extraction template in Covidence. Results: Cardiotoxicities associated with ICI have an average incidence rate of 1%. In several studies, the incidence of immune-related events was higher with dual therapy versus monotherapy. Myocarditis is the most common CAE with an incidence of 23% of all reported CAE, with pericardial disease, cardiogenic shock, accelerated atherosclerosis, and cardiovascular death also being reported following ICI therapies. Cardiotoxicities associated with CAR T-cell therapy have an average incidence rate of 24%. Cytokine release syndrome (CRS) is the most common effect in conjunction with high troponin levels in 66% of cases. Secondary to CRS, patients experienced hypotension, pericarditis, left ventricular systolic dysfunction, and arrhythmias. Concerning overall immunotherapy-related CAEs, the average mortality rate is 29% and the mean time to onset of symptoms is 89.5 days. Conclusions: The incidence of immunotherapy-related toxicities continues to rise due to increased survivorship and greater access to treatment. Given the low, yet severe and often irreversible incidence of these toxicities, (along with 77% of articles highlighting research gaps), there is a need to create a database that establishes comprehensive guidelines to improve patient outcomes and reduce toxicities. As of 2024, no such database exists for physicians to utilize. A proposed clinical study aims to track inflammatory cardiotoxic cases within the first 90 days of treatment and compare outcomes between monotherapy and dual immunotherapy approaches.