Mortality from immune checkpoint inhibitor-related myocarditis has halved in recent years, but the condition remains the top cardiovascular concern with these cancer therapies.
An international cardio-oncology panel has issued new guidance on managing the cardiac complications, reporting myocarditis deaths fell from 45% to 23% between 2016 and 2021-22.
The position statement, published in JAMA Oncology [link here], provides a framework for stratifying myocarditis severity and tailoring treatment accordingly.
“Myocarditis remains of highest concern, although fatality rates have declined over time with a broadening spectrum of presentations ranging from troponin elevation of uncertain significance to smouldering, nonsevere, and severe or fulminant myocarditis,” the authors wrote.
The panel identified key risk factors including dual ICI therapy, concurrent tyrosine kinase inhibitors, and certain cancer types such as melanoma and thymic epithelial tumours.
Management by severity
The statement categorises three myocarditis presentations:
Smouldering/subclinical: Patients meet diagnostic criteria but are asymptomatic. Stop ICIs but may restart after multidisciplinary review.
Nonsevere: Symptomatic without haemodynamic or electrical instability. Discontinue ICIs, start prednisone immediately, and monitor with telemetry.
Severe: Electrical or haemodynamic instability present. Admit to intensive care, stop ICIs, and start high-dose steroids immediately.
The authors stressed that elevated troponin alone shouldn’t trigger automatic ICI cessation or immunosuppression. Clinicians should consider a broad differential including acute coronary syndrome, sepsis, respiratory failure, and pulmonary embolism.
Restarting therapy
Data on ICI rechallenge after myocarditis remain very limited, the panel noted.
Rechallenge should only occur if myocarditis has fully resolved, minimal immunosuppression is required (ideally under 10mg daily prednisolone), and continuation of ICI therapy is compelling.
To reduce risk, clinicians should switch to monotherapy with a different ICI, avoid CTLA-4 inhibitors, and conduct serial troponin monitoring with periodic cardiac imaging.
Beyond myocarditis, the statement highlighted pericarditis, vasculitis, and aggravation of chronic inflammatory conditions such as atherosclerosis with acute ischaemic complications as potential ICI-related cardiovascular risks.
Overall immune-related adverse event mortality from ICIs fell from 14% to 7% between 2016 and 2021-22.
“Patients benefit from a multidisciplinary and nuanced approach to management that accounts for both the severity of the presentation and the importance of balancing toxic effect with the continuation of life-saving cancer treatment,” the authors said.
The statement was developed by experts in cardiology, oncology, and haematology on behalf of the International Cardio-Oncology Society.