Case Series of Steroid-Resistant Immune Checkpoint Inhibitor Associated Myocarditis: A Comparative Analysis of Corticosteroid and Tofacitinib Treatment

Cong Wang; Jinyi Lin; Yan Wang; David H Hsi; Jiahui Chen; Tianshu Liu; Yuhong Zhou; Zhenggang Ren; Zhaochong Zeng; Leilei Cheng; Junbo Ge

doi:10.3389/fphar.2021.770631

Case Series of Steroid-Resistant Immune Checkpoint Inhibitor Associated Myocarditis: A Comparative Analysis of Corticosteroid and Tofacitinib Treatment

Front Pharmacol. 2021 Dec 6:12:770631. doi: 10.3389/fphar.2021.770631. eCollection 2021.

Authors

Cong Wang¹, Jinyi Lin¹, Yan Wang², David H Hsi³, Jiahui Chen¹, Tianshu Liu², Yuhong Zhou², Zhenggang Ren⁴, Zhaochong Zeng⁵, Leilei Cheng⁶, Junbo Ge¹

Affiliations

¹ Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai, China.
² Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
³ Department of Cardiology, Stamford Hospital, Stamford, CT, United States.
⁴ Department of Liver Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
⁵ Department of Radiotherapy, Zhongshan Hospital, Fudan University, Shanghai, China.
⁶ Department of Echocardiography, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China.

Abstract

Background: Immune checkpoint inhibitor (ICI)-associated myocarditis is an uncommon and potentially fatal immune-related adverse event (irAE). Although corticosteroids are recommended as the first-line treatment by current guidelines, patients still have variable responses to it, and the guidelines vary significantly in terms of treatment strategies. Objectives: In this study, we performed a retrospective analysis of ICI-associated myocarditis in our hospital to propose a new comparative analysis to aid individualized treatment. Methods: We reviewed detailed records of 24 patients with confirmed ICI-associated myocarditis in our hospital from July 1, 2019, to April 1, 2021. Although all the cases in our study received recommended initial corticosteroid treatment according to the guidelines, different responses to corticosteroid were observed during the process of subsequent corticosteroid tapering. Basing on troponin cardiac troponin T rebound during corticosteroid tapering, we propose a new classification analysis of ICI-associated myocarditis that included two subgroups: corticosteroid-sensitive (n = 8) and corticosteroid-resistant group (n = 16). Results: Compared with corticosteroid-sensitive patients, larger doses of corticosteroid, longer period of treatment, and higher mortality rate were found in corticosteroid-resistant patients. Corticosteroid-resistant patients were characterized by more prominent ptosis, muscle weakness, elevated cardiac biomarkers, creatine kinase, and hepatic enzymes levels than that in the corticosteroid-sensitive patients. Tofacitinib (5 mg twice a day) was used in 11 corticosteroid-resistant patients, with seven patients recovered from ICI-associated myocarditis, showing a promising therapeutic effect. Conclusion: Our group analysis of corticosteroid responsiveness in patients with ICI-associated myocarditis may help clinicians to apply individualized treatment in this high-risk cohort. In addition, tofacitinib could provide clinical benefits when used early in the corticosteroid-resistant patients and may provide a new option for the treatment of ICI-associated myocarditis.

Keywords: cardiotoxicity; corticosteroid; immune checkpoint inhibitor; myocarditis; tofacitinib.