Editorial
doi: 10.1016/j.jaccao.2020.12.001.
eCollection 2021 Mar.
Management of Immune Checkpoint Inhibitor-Induced Myocarditis: The French Working Group's Plea for a Pragmatic Approach
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- PMID: 34396318
- PMCID: PMC8352226
- DOI: 10.1016/j.jaccao.2020.12.001
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Editorial
Management of Immune Checkpoint Inhibitor-Induced Myocarditis: The French Working Group's Plea for a Pragmatic Approach
JACC CardioOncol.
.
No abstract available
Keywords: cancer; immune checkpoint inhibitors; myocarditis.
Conflict of interest statement
Dr. Thuny has received modest fees for lectures outside the submitted work from Merck Sharp and Dohme, Bristol Myers Squibb, and Roche. Dr. Alexandre has received modest lecture fees outside the submitted work from Bristol Myers Squibb. Dr. Salem has received modest fees for serving on advisory boards from Bristol Myers Squibb; and shares a patent related to the use of CTLA4 agonists for the treatment of severe immune-related adverse reactions. Dr. Cohen-Solal has received fees for lectures or board participation, outside the submitted work, from Merck Sharp and Dohme. Dr. Cohen has received modest consultant and lecture fees outside the submitted work from Bristol Myers Squibb. Dr. Ederhy has received modest lecture fees outside the submitted work from Bristol Myers Squibb. Dr. Cautela has received modest lecture fees outside the submitted work from Merck Sharp and Dohme. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Figures
The French Working Group’s Pragmatic Approach for ICI CV Monitoring and Management of ICI-Induced Myocarditis ∗For monitoring, troponin testing should be carried out by the same laboratory (same assay and method of measurement). Troponin testing is considered positive if troponin I or T is >99th percentile of the upper reference limit. Concomitant myositis may result in significant elevations of creatine kinase (CK), CK isoforms, and even troponin T. Thus, troponin I would be the most specific option for myocardial injury. CK-myocardial band should be used if troponin I measurement is not available. In patients with pre-therapeutic troponin elevation, a 50% increase of the level may be used as a cutoff, but no evidence currently supports this recommendation. †We feel that electrocardiography (ECG) and troponin testing should be performed for at least 6 weeks after initiation of immune checkpoint inhibitor (ICI) therapy because most ICI-induced myocarditis episodes occur after the first cycles. This is a specific strategy suggested by the French Working Group of Cardio-Oncology. We acknowledge that there is a need for greater evidence, and thus far, the data to date do not strongly support this strategy. Moreover, we propose that ECG and troponin are performed within 48 h prior to each cycle. ‡Especially pericarditis, vasculitis, myositis, and myasthenia gravis. Immune toxicities can also affect the skin (maculopapular rash, vitiligo, psoriasis, Lyell syndrome, drug reaction with eosinophilia, and systemic symptoms), the gastrointestinal tract (enterocolitis, gastritis, pancreatitis, celiac disease), the endocrine glands (abnormal thyroid function, hypophysitis, adrenal insufficiency, diabetes), the lungs (pneumonitis, pleural effusion, sarcoidosis), the nervous system (peripheral neuropathy, aseptic meningitis, Guillain-Barré syndrome, encephalopathy, myelitis, meningoradiculoneuritis, myasthenia gravis), the liver (hepatitis), the kidney (granulomatous interstitial nephritis, lupus-like glomerulonephritis), hematological cells (hemolytic anemia, thrombocytopenia, neutropenia, pancytopenia), the musculoarticular system (arthritis, myopathies), the pericardium (pericarditis), the vessels (vasculitis), and the eyes (uveitis, conjunctivitis, blepharitis, retinitis, choroiditis, orbital myositis). §Including ECG, transthoracic echocardiogram, troponin, natriuretic peptides [NPs], CK, CK-myocardial band, and cardiovascular (CV) magnetic resonance imaging. Rule out acute coronary syndrome using coronary angiography or computed tomography according to the clinical context. Consider excluding acute pulmonary embolism. ||According to Bonaca diagnostic criteria (8) and clinical judgment. #Unfavorable course defined as hemodynamic instability OR electrical instability OR increasing troponin OR decreasing left ventricular ejection fraction. ∗∗There is a lack of data to recommend a standardized strategy for the intensification of immunosuppressive therapy. For now, case series and case reports have shown the potential efficacy of antithymocyte globulin, intravenous immunoglobulin, plasma exchange, mycophenolate mofetil, tacrolimus, tocilizumab, abatacept, alemtuzumab, and tofacitinib. The decision regarding optimal therapy must be multidisciplinary, involving specialists in immunology and organ rejection. Infliximab was also proposed but was not incorporated into the algorithm because of its contraindication in acute heart failure. ††2 mg/kg/day for 14 days, then 1 mg/kg/day for 14 days and then tapered over 4 to 6 weeks. Consider troponin monitoring at each dose change. i.v. = intravenous; irAE = immune-related adverse event.
References
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- Escudier M., Cautela J., Malissen N. Clinical features, management, and outcomes of immune checkpoint inhibitor-related cardiotoxicity. Circulation. 2017;136:2085–2087. - PubMed
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- Haanen J.B.A.G., Carbonnel F., Robert C. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28:iv119–iv142. - PubMed
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