Introduction: Immune checkpoint inhibitors (ICI) have transformed the management of many malignancies, superseding traditional chemotherapy agents. Although rare, activation of immunemediated myocarditis can quickly become life threatening and presents unique challenges due to heterogenous and varied presentations. Permanent discontinuation of ICI followed by
immunosuppressive therapy generally reverses myocarditis and preserves cardiac function. The growing interest in combining ICI with potentially cardiotoxic targeted therapies adds to this complexity.
Method: This series describes six patients with advanced melanoma who developed immune-mediated myocarditis whilst receiving an anti-PD-1 antibody or an anti-PD-L1 antibodies plus a mitogen-activated protein kinase kinase (MEK) inhibitor at Peter MacCallum Cancer Centre.
Results: Presentations ranged from asymptomatic cardiac enzyme elevation to death due to heart failure. We demonstrate the cardiac enzyme kinetics of five of the six patients and their responses to immunosuppressive therapy. We highlight the role of cardiac MRI (CMRI), a sensitive and non-invasive tool, for the early detection of myocardial inflammation. Five of the six patients exhibited CMRI changes consistent with myocarditis, including mid-wall myocardial oedema and late gadolinium enhancement in a non-coronary distribution. Critically, two of these patients had normal findings on echocardiograms. Of the five patients who received immunosuppression, four recovered from myocarditis, one improved with cardiac failure management alone, and one died of cardiac failure. Three of the four patients who responded to ICI derived long-term benefit.
Conclusion: Clinical pharmacovigilance, prompt multi-modal diagnosis, cardiac imaging, and multidisciplinary management is paramount for the treatment immune-mediated myocarditis.