Treatment strategy for myocarditis in patients using immune checkpoint inhibitors or combined anti-vascular endothelial growth factor therapy by clinical severity.

ABSTRACT

BACKGROUND: Combination of immune checkpoint inhibitor (ICI) and anti-vascular endothelial growth factor (VEGF) therapy has increasingly become a promising strategy in various tumors. However, the combination might be associated with increased cardiotoxicities. Myocarditis is a potentially fatal complication in cancer patients treated with ICI. Currently, there are no clear guidelines for the management of this disease nor data characterizing the clinical course of myocarditis patients due to the combination of ICI and anti-VEGF therapy. PATIENTS AND METHODS: This study included all patients consecutively admitted to Shanghai Zhongshan Hospital, Fudan University for the diagnosis of ICI-associated myocarditis according to Bonaca's criteria. The clinical presentation and outcome of myocarditis patients were collected receiving ICI and anti-VEGF combined therapy. RESULTS: A total of 48 patients were included (23 received combined treatment of ICI and anti-VEGF while 25 received ICI only). No differences in baseline characteristics, clinical course, and outcomes were observed among patients receiving ICI with or without anti-VEGF treatment. The patients were subdivided into 3 groups including 8 fulminant cases, 25 clinically significant cases, and 15 subclinical cases based on clinical severity. The fulminant group was associated with a higher rate of cardiovascular deaths (CVDs) compared with clinically significant and subclinical groups (87.5% versus 4.0% versus 0.0%, p < 0.01). When stratified by the dose of corticosteroids used, cases with high-dose usage were more likely to have a CVD when compared to low dose or no use and intermediate dose groups (0.0% versus 4.0% versus 57.1%, p < 0.01). CONCLUSIONS: No significant differences between myocarditis patients receiving ICI or combined anti-VEGF therapy in terms of clinical presentation and outcome were observed. Treatment strategy for myocarditis in patients using ICI or combined anti-VEGF therapy should be based on clinical severity. Specifically, immunosuppressive therapy besides high-dose corticosteroids is needed for fulminant cases.