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<p>Immune checkpoint inhibitors (ICIs) have significantly advanced cancer therapy. However, these therapies can disrupt immune self-tolerance, leading to immune-related adverse events, among which immune checkpoint inhibitor-related myocarditis (ICIrM) is associated with the highest mortality rates. Clinical presentation of ICIrM varies widely, ranging from asymptomatic cardiac biomarker elevation to fulminant heart failure. As such, uniform treatment guidelines may not be appropriate, and a personalized approach is essential. There is no universal consensus on routine screening; however, baseline ECG and echocardiography are recommended by most cardio-oncology guidelines. Serial cardiac biomarker monitoring may aid in early detection and intervention. Both cardiac troponin T and cardiac troponin I are sensitive for the diagnosis of ICIrM and prognosis of increased risk of major adverse cardiovascular events. Two diagnostic frameworks for ICIrM help clinicians in establishing diagnosis. Echocardiographic global longitudinal strain measurement provides a more sensitive risk assessment than traditional measures like ejection fraction. Cardiac MRI plays a critical role, offering high diagnostic accuracy. Endomyocardial biopsy confirms ICIrM and provides both diagnostic and prognostic information based on the presence or absence of myocyte necrosis. For confirmed ICIrM, corticosteroids remain the cornerstone of therapy, with high-dose regimens shown to reduce major adverse cardiovascular events. In steroid-refractory or severe cases, adjunctive immunomodulators such as mycophenolate mofetil, janus kinase inhibitors, and notably abatacept are utilized, although evidence is largely case-based. Abatacept, a CTLA-4 fusion protein, is the only drug under investigation in a randomized trial as a targeted therapy for ICIrM. In conclusion, ICIrM represents a diagnostic and therapeutic challenge due to its rarity, heterogeneous presentation, and the limitations of current tools. By describing the management of three illustrative real-life cases, this article aims to provide a framework for individualized management of ICIrM in adults, integrating current guidelines, literature, and clinical experience. Continued research and prospective trials are critical to refine diagnostic algorithms and improve patient outcomes.</p>

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How should immune checkpoint inhibitor myocarditis be treated?

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月17日

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  • Sally Badaan,
  • Adi Abbass,
  • Svetlana Tov,
  • Gil Bar-Sela,
  • Naiel Bisharat

摘要

Immune checkpoint inhibitors (ICIs) have significantly advanced cancer therapy. However, these therapies can disrupt immune self-tolerance, leading to immune-related adverse events, among which immune checkpoint inhibitor-related myocarditis (ICIrM) is associated with the highest mortality rates. Clinical presentation of ICIrM varies widely, ranging from asymptomatic cardiac biomarker elevation to fulminant heart failure. As such, uniform treatment guidelines may not be appropriate, and a personalized approach is essential. There is no universal consensus on routine screening; however, baseline ECG and echocardiography are recommended by most cardio-oncology guidelines. Serial cardiac biomarker monitoring may aid in early detection and intervention. Both cardiac troponin T and cardiac troponin I are sensitive for the diagnosis of ICIrM and prognosis of increased risk of major adverse cardiovascular events. Two diagnostic frameworks for ICIrM help clinicians in establishing diagnosis. Echocardiographic global longitudinal strain measurement provides a more sensitive risk assessment than traditional measures like ejection fraction. Cardiac MRI plays a critical role, offering high diagnostic accuracy. Endomyocardial biopsy confirms ICIrM and provides both diagnostic and prognostic information based on the presence or absence of myocyte necrosis. For confirmed ICIrM, corticosteroids remain the cornerstone of therapy, with high-dose regimens shown to reduce major adverse cardiovascular events. In steroid-refractory or severe cases, adjunctive immunomodulators such as mycophenolate mofetil, janus kinase inhibitors, and notably abatacept are utilized, although evidence is largely case-based. Abatacept, a CTLA-4 fusion protein, is the only drug under investigation in a randomized trial as a targeted therapy for ICIrM. In conclusion, ICIrM represents a diagnostic and therapeutic challenge due to its rarity, heterogeneous presentation, and the limitations of current tools. By describing the management of three illustrative real-life cases, this article aims to provide a framework for individualized management of ICIrM in adults, integrating current guidelines, literature, and clinical experience. Continued research and prospective trials are critical to refine diagnostic algorithms and improve patient outcomes.