Cardiac Monitoring Recommendations for Patients Receiving Opdualag (Nivolumab and Relatlimab)
Patients receiving Opdualag (nivolumab and relatlimab) should undergo baseline cardiac assessment with electrocardiogram (ECG) and echocardiography before treatment initiation, followed by periodic monitoring of cardiac function every 3 months during treatment due to the increased risk of cardiac adverse events, particularly myocarditis.
Background
Opdualag is a fixed-dose combination immunotherapy containing nivolumab (anti-PD-1) and relatlimab (anti-LAG-3) approved for treatment of unresectable or metastatic melanoma. Recent pharmacovigilance data indicates that this combination carries specific cardiac risks that require monitoring.
Pre-Treatment Cardiac Assessment
Baseline Evaluation
- Complete cardiac history and risk factor assessment
- 12-lead ECG
- Echocardiography to assess left ventricular ejection fraction (LVEF)
- Consider cardiac biomarkers (troponin, BNP or NT-proBNP)
Risk Stratification
Patients with pre-existing cardiovascular conditions require more intensive monitoring:
- History of cardiovascular disease
- Hypertension, diabetes, hyperlipidemia
- Previous cardiotoxic therapy (especially anthracyclines)
- Age >60 years
Monitoring Protocol During Treatment
Standard Monitoring Schedule
- ECG and cardiac biomarkers (troponin, BNP) every 3 months 1
- Echocardiography every 3 months during treatment 1
- Additional monitoring at treatment completion
Enhanced Monitoring for High-Risk Patients
- More frequent monitoring (every 4-8 weeks) for patients with:
- Pre-existing cardiac disease
- Abnormal baseline cardiac assessment
- Development of cardiac symptoms
Warning Signs Requiring Immediate Evaluation
- New-onset chest pain or discomfort
- Dyspnea or shortness of breath
- Palpitations or irregular heartbeat
- Unexplained fatigue
- Peripheral edema
- Syncope or pre-syncope
Management of Cardiac Adverse Events
LVEF Reduction
For asymptomatic LVEF decrease of ≥10% from baseline or drop to <50%:
- Cardiology consultation (preferably cardio-oncology)
- Consider cardioprotective medications (ACE inhibitors, beta-blockers)
- Reassess LVEF within 3-6 weeks 1
- Consider temporary treatment interruption if LVEF <40%
Myocarditis
- Immediate treatment interruption
- Urgent cardiology consultation
- High-dose corticosteroids
- Daily troponin monitoring until stabilization
QTc Prolongation
- If QTc >440 ms, increase monitoring frequency
- If QTc >500 ms or prolongation >50 ms from baseline, temporarily discontinue treatment and obtain cardiology consultation 1
- Check and correct electrolyte abnormalities
Special Considerations
Biomarker-Guided Monitoring
- Elevated troponin may identify early cardiotoxicity before LVEF changes 1
- Consider troponin assessment with each treatment cycle for high-risk patients
Imaging Modalities
- Echocardiography is preferred for routine monitoring
- Consider cardiac MRI for confirmation of suspected myocarditis or when echocardiography is inconclusive 1
- Global longitudinal strain (GLS) may detect subclinical cardiac dysfunction earlier than LVEF when available 1
Recent Evidence on Opdualag-Specific Cardiac Risks
Recent pharmacovigilance data from the FDA Adverse Event Reporting System indicates that nivolumab plus relatlimab (NIVO-RELA) is associated with increased risks for cardiac disorders (ROR = 2.84) compared to other immunotherapy combinations, with specific risks for myocarditis and troponin elevation 2. This underscores the importance of dedicated cardiac monitoring for patients receiving this combination.
While general immunotherapy cardiac monitoring guidelines provide a framework, the specific cardiac risk profile of Opdualag warrants particular attention to early detection of myocarditis and other cardiac adverse events through regular biomarker assessment and cardiac imaging.