Mycophenolate mofetil as second-line therapy for steroid-refractory ICI-induced myocarditis

Introduction Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events, including myocarditis, a rare yet potentially fatal condition. Current guidelines recommend nonsteroidal immunomoduladors for patients unresponsive to corticosteroids; however, optimal second-line treatments remain undefined. Purpose To evaluate the clinical characteristics and outcomes of patients treated with mycophenolate mofetil (MMF) due to ICI-induced myocarditis. Methods A retrospective, single-center analysis of all patients admitted with ICI myocarditis between January 2020 and December 2024 was conducted. Steroid-refractory myocarditis was defined as persistent symptoms and/or failure of cardiac biomarkers to decrease after appropriate therapy. Patients meeting these criteria and without hemodynamic instability or respiratory failure received MMF as a second-line immunosuppressant. Data collected included demographics, ICI regimen, time to myocarditis onset, presenting symptoms, laboratory findings, imaging, treatment, and clinical outcomes. Results Among 13 patients diagnosed with ICI myocarditis during the study period, 5 (38%) were identified as steroid-refractory and received MMF. Our cohort had a mean age of 70.6 ± 7.6 years, with a predominance of males (85%). The majority had no prior history of cardiac disease (92%). Combination ICI therapy was administered in 23% of cases. The average number of ICI cycles before myocarditis onset was 2.7 ± 2.2. Neurological symptoms were present in 61% of patients, and 54% exhibited other immune-related toxicities. At diagnosis, patients exhibited significant elevations in cardiac biomarkers: mean peak troponin T was 1048.0 ± 710.6 ng/L, and mean peak creatine kinase was 2125.5 ± 2561.3 U/L. The mean left ventricular ejection fraction (LVEF) was 58.3% ± 9.9%. New-onset conduction abnormalities were observed in 54% of patients. Cardiac magnetic resonance imaging (available in 8 patients) revealed myocarditis in 7 cases. There were no significant differences between the MMF and non-MMF groups in baseline characteristics. The MMF-group patients were more frequently treated with intravenous immunoglobulin (80% vs 37%). Following MMF administration, a rapid decline in cardiac biomarkers was noted in all cases, indicating a favorable response. In-hospital mortality was 31% overall, with a lower rate in the MMF group (20%) compared to those not receiving MMF (37%). During follow-up, mortality was 54%, with 40% in the MMF group versus 62% in the non-MMF group. Conclusions In our population with steroid-refractory ICI-induced myocarditis, MMF demonstrated potential as an effective second-line therapy. Given the absence of randomized controlled trials, our study provides valuable clinical insights, suggesting that MMF may offer a beneficial therapeutic option for patients unresponsive to corticosteroids. Further prospective studies are warranted to confirm these observational data.Baseline characteristics by MMF