Ipilimumab- and nivolumab-induced myocarditis in a patient with metastatic cholangiocarcinoma: a case report

Abstract

Background Myocarditis in patients treated with immune checkpoint inhibitors has previously been reported to be rare, though it has most likely been underreported owing to misdiagnosis in the absence of overt clinical presentation. Early detection and characterization of this potentially life-threatening immune-related adverse event is of major importance. Herein we report a case of early-onset myocarditis in an asymptomatic patient treated with dual checkpoint inhibition for metastatic cholangiocarcinoma. Case presentation A 69-year-old male Caucasian patient with metastatic cholangiocarcinoma presented with mild epigastric pain and troponinemia prior to the third dose of dual checkpoint inhibition (ipilimumab 1 mg/kg body weight and nivolumab 3 mg/kg body weight). Initial workup showed no significant abnormalities (physical/neurological examination, electrocardiogram, 72-hour Holter monitoring, and a transthoracic echocardiogram). However, cardiac magnetic resonance imaging revealed a zone of contrast enhancement in the inferior segment of the left ventricular wall indicating a recent episode of myocarditis. Despite steroid initiation (0.5 mg/kg oral prednisolone per day), troponin levels kept increasing, in the absence of coronary disease, for which steroids were increased to 1.5 mg/kg/day. Fluorodeoxyglucose positron emission tomography/computed tomography, 28 days after detecting elevated troponin levels, depicted multiple zones of active myocardial inflammation (basal septal, mid-anterior, and apical inferior). The patient is currently stable, and troponinemia is slowly decreasing while steroids are steadily being tapered. Conclusion As the number of cancers treated with immune checkpoint inhibitors is expanding, the incidence of immune checkpoint inhibitor-induced myocarditis is likely to increase. Moreover, the emerging combination of immune checkpoint inhibitors with non-immune checkpoint inhibitor therapies with potential synergistic cardiotoxic side effects (for example, tyrosine kinase inhibitors) will further complicate the diagnosis of immune-related cardiotoxicity. This case highlights the urgent need for predictive biomarkers to stratify patients at risk and to develop a standardized and multidisciplinary management approach for early diagnosis and treatment of this severe immune-related adverse event.

A Systematic Review of Myocarditis Induced by Immune Checkpoint Inhibitors: How Concerning Is the Most Common Cardiotoxicity of Immune Checkpoint Inhibitors?

“…The second group of these drugs is CTLA-4 inhibitors, including ipilimumab, which is the first FDA-approved ICI [22]. A combination of these two groups, specifically ipilimumab and nivolumab, is used to fight cancer, and some studies report myocarditis with this combination [20][21][22]28]. The pathophysiology of myocarditis-related ICIs is still under research, as the inflammation can cause severe problems such as heart failure as well as other major cardiac events with a high rate of mortality.…”