A closer look at immune-mediated myocarditis in the era of combined checkpoint blockade and targeted therapies

Guo, Christina; Alexander, Marliese; Dib, Youseph; Lau, Peter K. H.; Weppler, Alison M.; Au-Yeung, George; Lee, Belinda; Khoo, Christine; Mooney, D.; Joshi, S.; Creati, Louise; Sandhu, Shahneen

doi:10.1016/j.ejca.2019.09.009

Cited by 36 publications

(47 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, clear consensus on the optimal dose of corticosteroids (the first-line treatment to start as an immunosuppressive) and on how and when to add other immunosuppressive agents has not been reported yet. In this regard, the initial dose of corticosteroid [(methyl) prednisolone] is usually recommended as 1–2 mg/kg in the present study ( 6 , 7 , 9 ). Some studies showed strong association of high-dose steroid therapy with a significantly lower rate of major adverse cardiac events ( 6 , 7 ).…”

Section: Introductionmentioning

confidence: 99%

“…Clinical presentation generally ranges from an asymptomatic elevation of cardiac enzymes to sudden death due to heart failure. Accordingly, symptoms generally present with a heterogeneous clinical spectrum that might include dyspnea (usually accompanied by a reduced left ventricular ejection fraction (LVEF) value), palpitations, nausea, fatigue, weight loss, and chest pain ( 6 ). In full-blown cases, all aspects of an acute heart failure scenario are usually fully established.…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, another study by Atallah-Yunes et al ( 17 ) reported that 93% of subjects with fatal myocarditis received only one or two doses of ICI. Of note, previous cases of immune myocarditis were reported to develop even within the first 15 days of therapy, particularly in those who had received combination therapy (ICI+tyrosine kinase inhibitors (TKI) and/or previous PD-1 inhibition) ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

“…Although no strong evidence-based recommendations has been reported, suppression of high-grade inflammatory response within the myocardium largely through immunosuppressive agents has been suggested as a milestone in the treatment of ICI-associated myocarditis ( 24 , 30 , 33 , 34 ). Within this context, even though corticosteroids ( 7 ) appear to be the basis of immunosuppressive therapy, cases have been reported where treatment regimens including antithymocyte globulin ( 6 ), mycophenolate mofetil ( 6 ), abatacept ( 33 ), alemtuzumab ( 34 ), tacrolimus ( 30 ), and rituximab ( 30 ) have been initiated depending on LVEF, hs-troponin level along with hemodynamic status. The common mechanism of action of these agents is to induce the inactivation or destruction of T cells, that are considered to play a pivotal role in the evolution of myocarditis, as confirmed by endomyocardial biopsy findings of patients with ICI-related myocarditis.…”

Section: Introductionmentioning

confidence: 99%

“…In ICI-related myocarditis with left ventricular systolic dysfunction, heart failure treatment as per current guidelines should be immediately started ( 6 ). However, clear consensus on the optimal dose of corticosteroids (the first-line treatment to start as an immunosuppressive) and on how and when to add other immunosuppressive agents has not been reported yet.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Myocarditis associated with immune check-point inhibitors: Practical considerations in diagnosis and management

Gürdoğan¹

2020

Anatol J Cardiol

View full text Add to dashboard Cite

Immune checkpoint inhibitors (ICI) have caused radical changes in the treatment scheme of many types of cancer in the past 10 years. ICIs are specific monoclonal antibodies that increase T-cell mediated immune response against cancer cells. Despite important advances in cancer treatment, uncontrolled activation of cytotoxic T cells has brought along many autoimmune clinical side effects, especially acute myocarditis. Although the incidence of ICI-related myocarditis is about 1%, it is remarkable in terms of mortality rate reaching 46% and demonstrating the necessity of rapid diagnosis and multidisciplinary approach. The present review aimed to summarize the heterogeneous symptomatology of ICI-associated myocarditis, clinical presentation ranging from elevated asymptomatic cardiac enzyme levels to cardiogenic shock, prominent diagnostic value of cardiac magnetic resonance imaging, and current information on the effectiveness of immunosuppressants in therapy.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Myocarditis associated with immune check-point inhibitors: Practical considerations in diagnosis and management

Gürdoğan¹

2020

Anatol J Cardiol

View full text Add to dashboard Cite

show abstract

Prognostic value of cardiovascular magnetic resonance in immune checkpoint inhibitor‐associated myocarditis: A systematic review and meta‐analysis

Song,

Zhang,

et al. 2024

Cancer Innovation

View full text Add to dashboard Cite

BackgroundImmune checkpoint inhibitors (ICI) are increasingly used in the first‐line treatment of malignant tumors. There is increasing recognition of their cardiotoxicity and, in particular, their potential to lead to myocarditis. Cardiovascular magnetic resonance (CMR) can quantify pathological changes, such as myocardial edema and fibrosis. The purpose of this systematic review and meta‐analysis was to examine the evidence for the roles of CMR in predicting prognosis in ICI‐associated myocarditis.MethodsPubMed, Cochrane Library, and Web of Science databases were searched until October 2023 for published works investigating the relationship between CMR parameters and adverse events in patients with ICI‐associated myocarditis. The analysis included studies reporting the incidence of late gadolinium enhancement (LGE), T1 values, T2 values, and CMR‐derived left ventricular ejection fraction (LVEF). Odds ratios (OR) and weighted mean differences (WMD) were combined for binary and continuous data, respectively. Newcastle‐Ottawa Scale was used to assess the methodological quality of the included studies.ResultsFive cohort studies were included (average age 65–68 years; 25.4% female). Of these, four studies were included in the meta‐analysis of LGE‐related findings. Patients with major adverse cardiovascular events (MACE) had a higher incidence of LGE compared with patients without MACE (OR = 4.18, 95% CI: 1.72–10.19, p = 0.002). A meta‐analysis, incorporating data from two studies, showed that patients who developed MACE exhibited significantly higher T1 value (WMD = 36.16 ms, 95% CI: 21.43–50.89, p < 0.001) and lower LVEF (WMD = − 8.00%, 95% CI: −13.60 to −2.40, p = 0.005). Notably, T2 value (WMD = −0.23 ms, 95% CI: −1.86 to −1.39, p = 0.779) was not associated with MACE in patients with ICI‐related myocarditis.ConclusionsLGE, T1 value, and LVEF measured by CMR imaging have potential prognostic value for long‐term adverse events in patients with ICI‐related myocarditis.

show abstract

Value of troponin T versus I in the diagnosis of immune checkpoint inhibitor‐related myocarditis and myositis: rechallenge?

et al. 2023

View full text Add to dashboard Cite

A 54-year old patient with metastatic melanoma presented with asymptomatic myositis and myocarditis after combined immune checkpoint inhibitors (ICI) therapy (anti-programmed cell death receptor-1, anti-lymphocyte activating gene-3, and anti-indoleamine 2,3-dioxygenase-1). The diagnosis was based on the typical time window after ICI, recurrence upon rechallenge, elevations of CK, high-sensitive troponin T (hs-TnT) and I (hs-TnI), mild NT-proBNP increase, and positive magnetic resonance imaging criteria. Notably, hsTnI was found to more rapidly increase and fall and to be more heart-specific than TnT in the context of ICI-related myocarditis. This led to ICI therapy withdrawal and switch to a less effective systemic therapy. This case report highlights the differential value of hs-TnT and hs-TnI for diagnosis and monitoring of ICI-related myositis and myocarditis.

show abstract

A closer look at immune-mediated myocarditis in the era of combined checkpoint blockade and targeted therapies

Abstract: term benefit. Clinical vigilance, prompt multimodal diagnosis and multidisciplinary management are paramount for the treatment of immune-mediated myocarditis.

Cited by 36 publications

References 38 publications

Myocarditis associated with immune check-point inhibitors: Practical considerations in diagnosis and management

Myocarditis associated with immune check-point inhibitors: Practical considerations in diagnosis and management

Prognostic value of cardiovascular magnetic resonance in immune checkpoint inhibitor‐associated myocarditis: A systematic review and meta‐analysis

Value of troponin T versus I in the diagnosis of immune checkpoint inhibitor‐related myocarditis and myositis: rechallenge?

Contact Info

Product

Resources

About