| 9.1. Myocarditis, pericarditis, arrhythmias, impaired ventricular function with heart failure, and vasculitis |
Work-up and evaluation: - ECG.
- Troponin, and CPK to rule out concurrent myositis, especially in patients treated with combination immune therapies. Alternative reasons for elevation should be ruled out.
- If elevated, troponin should be serially monitored. With elevated troponin, be aware of the potential for triple M irAEs – myositis, myasthenia, and myocarditis – and refer to subspecialties.
- BNP.
- Echocardiogram.
- Chest radiograph.
Additional testing to be guided by cardiology and may include: - Stress test.
- Cardiac catheterization.
- Cardiac MRI.
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| Grading | Management |
G1: Abnormal cardiac biomarker testing without symptoms and with no ECG abnormalities.
G2: Abnormal cardiac biomarker testing with mild symptoms or new ECG abnormalities without conduction delay.
G3: Abnormal cardiac biomarker testing with either moderate symptoms or new conduction delay.
G4: Moderate to severe decompensation, IV medication or intervention required, life-threatening conditions. | - All grades warrant work-up and intervention, given the potential for cardiac compromise.
- Hold ICPi for G1 elevated troponin¶ and recheck troponin 6 hours later. May consider resuming once normalized or if believed not to be related to ICPi.
- Hold ICPi and discontinue for ≥G2:
- For patients with grade ≥2, early (ie, within 24 hours) initiation of high-dose corticosteroids (prednisone 1 to 2 mg/kg/day, oral or IV equivalent depending on symptoms) should be considered as it is likely to be beneficial without adverse effects.
- Admit patient for cardiology consultation.
- Management of cardiac symptoms according to ACC/AHA guidelines and with guidance from cardiology.
- Immediate transfer to a coronary care unit should be considered for patients with elevated troponin or conduction abnormalities.
- For new conduction delay, consider a pacemaker.
- In patients without an immediate response to high-dose corticosteroids, consider early institution of cardiac transplant rejection doses of corticosteroids (methylprednisolone 1 g every day) and the addition of either mycophenolate, infliximab, or antithymocyte globulin. Consider abatacept (costimulatory molecule blockade) or alemtuzumab (CD52 blockade) as additional immunosuppression in life-threatening cases.
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Qualifying statement: - Treatment recommendations are based on anecdotal evidence and the life-threatening nature of cardiovascular complications. Holding checkpoint inhibitor therapy is recommended for all grades of complications. The appropriateness of rechallenging remains unknown. Note that infliximab has been associated with heart failure and is contraindicated at high doses (ie, >5 mg/kg) in patients with moderate-severe heart failure.
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| 9.2. Venous thromboembolism |
Work-up and evaluation: - Evaluation of signs and symptoms of PE or DVT may include:
- Clinical prediction rule to stratify patients with suspected VTE.
- Venous ultrasound for suspected DVT.
- CTPA for suspected PE.
- Can also consider D-dimer for low-risk patients based on risk stratification by clinical prediction rule for DVT/PE when CT or Doppler not available or appropriate.
- V/Q scan is also an option when CTPA is not appropriate.
- Consider other testing, including ECG, chest radiography, BNP and troponin levels, and ABG.
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| Grading | Management |
| G1: Venous thrombosis (eg, superficial thrombosis). | - Continue ICPi.
- Warm compress.
- Clinical surveillance.
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| G2: Venous thrombosis (eg, uncomplicated deep vein thrombosis), medical intervention indicated. | - Continue ICPi.
- Management according to CHEST, ACC, and/or AHA guidelines and consider consult from cardiology or other relevant specialties.
- LMWH, VKA, dabigatran, rivaroxaban, apixaban, or edoxaban for initial anticoagulation treatment. For long-term anticoagulation, LMWH, edoxaban, rivaroxaban, or apixaban for at least 6 months are preferred over VKAs because of improved efficacy.
- IV heparin is an acceptable alternative for initial use and oral anticoagulants are acceptable for the long term.
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| G3: Venous thrombosis (eg, uncomplicated PE), urgent medical intervention indicated. | - Hold ICPi and may reintroduce after risk and benefit are considered.
- Follow G2 anticoagulation recommendations.
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| G4: Life-threatening consequences; hemodynamic or neurologic instability; organ damage; loss of extremity(ies). | - Hold ICPi and may reintroduce after risk and benefit are considered.
- Admit patient and management according to CHEST, ACC, and/or AHA guidelines and with guidance from cardiology.
- Respiratory and hemodynamic support.
- Follow G2 anticoagulation recommendations with further clinical management as indicated based on symptoms.
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Additional considerations: - VTE prophylaxis in high-risk outpatients with cancer (Khorana score of 2 or higher before starting a new systemic regimen) may be offered thromboprophylaxis with apixaban, rivaroxaban, or LMWH, provided there are no significant risk factors for bleeding and no drug interactions, as per ASCO VTE guideline.
- Although it may be impossible to determine the etiology of thromboembolic disease in patients with advanced cancer and the role, if any, that ICPi treatment plays, it is reasonable to remove the potential inciting agents, given the severity and life-threatening potential of grade 4 complications. Clinicians are to use clinical judgment and take into account the risks and benefits when deciding whether to discontinue ICPi treatment.
- Anticoagulant therapy duration should continue while on immunotherapy and consideration be given to continuing for an additional 6 months following completion of immunotherapy.
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