Immune checkpoint inhibitor–associated myocarditis

Osinga, Thamara E.; Oosting, Sjoukje F.; Meer, Peter van der; Boer, Rudolf A. de; Kuenen, B.; Rutgers, Abraham; Bergmann, Lothar; Munnink, Thijs H. Oude; Jalving, Mathilde; Kruchten, Michel van

doi:10.1007/s12471-021-01655-7

Cited by 8 publications

(4 citation statements)

References 34 publications

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“…Considering that myocarditis may be refractory to treatment, a careful long-term follow-up with troponin is required. Few cases have reported changes in troponin levels over time in patients with ICI-related myocarditis alone ( Norwood et al, 2017 ; Ida et al, 2022 ; Osinga et al, 2022 ). In these cases, high troponin levels were found to prolong after the initiation of steroid therapy.…”

Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Inhibitor-Related Myositis Overlapping With Myocarditis: An Institutional Case Series and a Systematic Review of Literature

et al. 2022

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Background: Immune checkpoint inhibitor (ICI)-related myositis with myocarditis is a rare but potentially fatal immune-related adverse event. However, its clinical features, response to immunosuppressive treatment, and prognosis remain poorly understood. Here, we describe the clinical course of patients with ICI-related myositis overlapping with myocarditis treated at our institution and a systematic review focusing on the response to immunosuppressive therapy.Methods: We identified patients who developed ICI-induced myositis with myocarditis and were treated at our hospital using a retrospective chart review of electronic medical records. For the systematic review, studies reporting ICI-induced myositis with myocarditis were identified using the Cochrane Library and PubMed databases.Results: Of the 625 patients treated with ICIs, four developed myositis with concurrent myocarditis. All the patients received immunosuppressive therapy. We assessed the activity of myocarditis and myositis based on temporal changes in troponin and creatine kinase (CK) levels. In all patients, peak troponin values appeared later than the peak CK values (median, 17 days). The median time from the start of ICI therapy to the peak of troponin and CK levels was 42.5 and 28 days, respectively. In all patients, CK levels decreased rapidly and steadily after the initiation of immunosuppressants. However, troponin levels were unstable and increased. In all patients, CK levels normalized within one month (range, 12–27 days), but troponin levels took several months to normalize (range, 84–161 days). Fourteen cases of ICI-related myositis with myocarditis were included in the systematic review. Of the 14 cases, 12 (86%) had their CK level decreased after the initial steroid treatment, but the troponin level increased and was higher than that before the start of treatment. In addition, the peak troponin values appeared later than the peak CK values (a median of 6.5 days). Eight (89%) of 9 long-term follow-up patients had troponin levels above the normal range even after CK normalization.Conclusion: In most cases of ICI-related myositis with myocarditis, troponin levels increased after the initial steroid treatment despite decreased CK levels, and exceeded pre-steroid levels. In addition, troponin remained elevated for several months after CK normalized.

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Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Inhibitor-Related Myositis Overlapping With Myocarditis: An Institutional Case Series and a Systematic Review of Literature

et al. 2022

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“…Additionally, our case makes evident the importance of interdisciplinary teams for optimal management of such patients. By reviewing the case in our well-established CIO iTox Board, we swiftly coordinated diagnostics and early immunosuppression, which data suggests is critical for patients’ outcomes ( 4 , 5 , 10 ). With the ever-growing number of ICI-based treatments and expansion beyond targeting PD-1 and CTLA-4, such interdisciplinary teams will become increasingly important in the future to manage these patients’ therapies, especially when irAEs occur.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…With a reported incidence between 0.04% and 1.14%, ICI-related myocarditis (irMyocarditis) is a relatively rare, yet potentially lethal immune-related adverse effect (irAE) ( 2 ). Importantly, irMyocarditis is considered an early irAE, with a median occurrence of 17 to 34 days after treatment initiation, and 76% of cases develop within the first six weeks of ICI ( 3 – 5 ). However, in the following, we present a rare case of histologically confirmed near fatal irMyocarditis, which occurred after over 2.5 years of pembrolizumab treatment.…”

Section: Introductionmentioning

confidence: 99%

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Case Report: Sudden very late-onset near fatal PD1 inhibitor-associated myocarditis with out-of-hospital cardiac arrest after >2.5 years of pembrolizumab treatment

Lewis,

Seuthe,

Lennartz

et al. 2024

Front. Cardiovasc. Med.

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IntroductionImmune checkpoint inhibitors have advanced the outcomes of many different types of cancer. A rare but extraordinarily severe complication of these agents resembles immune checkpoint inhibitor-related myocarditis, which typically occurs within the first few weeks after treatment initiation with a mortality of 25%–50%.Case reportA 57-year-old woman had uneventfully received pembrolizumab for metastatic non-small cell lung cancer for over 2.5 years and was admitted after an out-of-hospital cardiac arrest due to ventricular fibrillation. After successful cardiopulmonary resuscitation, the initial diagnostic work-up showed elevated cardiac enzymes and a limited left-ventricular ejection fraction, while coronary angiography did not show relevant stenosis. Despite cardiac MRI being unsuggestive of myocarditis, myocardial biopsies were obtained and histologically confirmed anti-PD-1 antibody-associated myocarditis. After the initiation of prednisone at 1 mg/kg body weight, the patient gradually recovered and was discharged three weeks later with markedly improved cardiac function.ConclusionThis case resembles the first description of a very late onset irMyocarditis, occurring over 2.5 years after the start of treatment. It demonstrates the importance of contemplating that severe immune-related toxicities with a sudden onset clinical presentation may occur even after long uneventful periods of anti-PD-1 immune checkpoint inhibitor treatment. Furthermore, it underlines the critical importance of myocardial biopsies in this setting, especially when cardiac MRI remains inconclusive. Moreover, it demonstrates the necessity and benefits of early immunosuppressive treatment if immune-related myocarditis is considered a differential diagnosis.

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Role of Biomarkers in the Management of Immune-Checkpoint Inhibitor-Related Myocarditis

et al. 2023

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Immune checkpoint inhibitor–associated myocarditis

Cited by 8 publications

References 34 publications

Immune Checkpoint Inhibitor-Related Myositis Overlapping With Myocarditis: An Institutional Case Series and a Systematic Review of Literature

Immune Checkpoint Inhibitor-Related Myositis Overlapping With Myocarditis: An Institutional Case Series and a Systematic Review of Literature

Case Report: Sudden very late-onset near fatal PD1 inhibitor-associated myocarditis with out-of-hospital cardiac arrest after >2.5 years of pembrolizumab treatment

Role of Biomarkers in the Management of Immune-Checkpoint Inhibitor-Related Myocarditis

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