Early evaluation of severe immune checkpoint inhibitor-associated myocarditis: a real-world clinical practice

Tang, Xin; Li, Yuan; Huang, He; Shi, Rui; Shen, Li-Ting; Qian, Wen-Lei; Yang, Zhi-Gang

doi:10.1007/s00432-023-04782-3

Cited by 5 publications

(5 citation statements)

References 30 publications

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“…Tang et al. 9 also noted that ICI treatment cycles, ICI types, and concurrent systematic therapies did not increase the risk of severe ICI‐associated myocarditis. Additionally, a noteworthy finding of our study was that concurrent targeted therapy did not increase myocarditis severity, but it reduced the risk of severe ICI‐associated myocarditis.…”

Section: Discussionmentioning

confidence: 98%

“…Thus far, some serum or echocardiographic markers have been reported to predict severe ICI‐associated myocarditis. 9 , 10 However, few studies were focused on comparing patients with mild and severe myocarditis and most studies explored the predictive value of fewer electrocardiographic parameters.…”

Section: Discussionmentioning

confidence: 99%

“…Tang et al. 9 retrospectively analyzed the clinical characteristics of patients with ICI‐associated myocarditis and reported several predictors of severe ICI‐associated myocarditis. However, they did not found that ECG abnormalities were associated with the severity of ICI‐associated myocarditis.…”

Section: Discussionmentioning

confidence: 99%

“…Only a few studies have reported differences in clinical characteristics between patients with mild and severe myocarditis. 9 , 10 Electrocardiogram (ECG) is a simple, economical, and noninvasive test and can be chosen as the first‐line tool for detecting cardiovascular abnormalities in ICI users, particularly those with cardiac arrhythmias. Some studies reported the ECG changes in patients with ICI‐associated myocarditis, including low QRS voltage, pathological Q waves, and prolonged QRS interval.…”

Section: Introductionmentioning

confidence: 99%

“… 11 , 12 , 13 , 14 However, very few investigations have reported differences in electrocardiographic manifestations between patients with mild and severe ICI‐associated myocarditis. 9 , 15 Therefore, to recognize severe myocarditis at an early stage and improve patent prognosis, there is an urgent requirement to determine the electrocardiographic characteristics of severe ICI‐associated myocarditis compared with mild ICI‐associated myocarditis.…”

Section: Introductionmentioning

confidence: 99%

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Early identification of severe immune checkpoint inhibitor associated myocarditis: From an electrocardiographic perspective

Gao,

Zhang,

Qiu

et al. 2024

Cancer Medicine

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ObjectivesImmune checkpoint inhibitor (ICI)‐associated myocarditis, particularly severe ICI‐associated myocarditis, has a high mortality rate. However, the predictive value of electrocardiogram (ECG) remains unclear. The present study aimed to evaluate the predictive value of clinical and electrocardiographic parameters for severe myocarditis.MethodsClinical and electrocardiographic data of 73 cancer patients with ICI‐associated myocarditis were retrospectively collected. The severity of ICI‐associated myocarditis was graded using the NCCN guidelines for managing immunotherapy‐related toxicities. Myocarditis grades 1–2 and grades 3–4 were classified as mild and severe myocarditis, respectively. Logistic regression analysis was performed to analyze the predictive value of each parameter in predicting severe myocarditis.ResultsAmong the 73 patients with myocarditis, 20 (27.4%) patients had severe myocarditis. Compared with mild myocarditis group, sinus tachycardia (p = 0.001), QRS duration ≥110 ms (p = 0.001), prolonged QTc interval (p < 0.001), and bundle branch block (p = 0.007) at the time of myocarditis were more common in the severe myocarditis group. Logistic regression analysis revealed that sinus tachycardia (p = 0.028) and QTc interval prolongation (p = 0.007) were predictors of severe myocarditis. Whereas the predictive value of other electrocardiographic parameters was weak. Concurrent targeted therapy didn't increase the risk of severe myocarditis. A high NT‐proBNP level was associated with severe myocarditis.ConclusionsECG at the onset of myocarditis manifested as sinus tachycardia and prolonged QTc interval predicted a high risk of severe myocarditis. Early detection of ECG abnormalities may faciliate early detection of severe ICI‐associated myocarditis.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Early identification of severe immune checkpoint inhibitor associated myocarditis: From an electrocardiographic perspective

Gao,

Zhang,

Qiu

et al. 2024

Cancer Medicine

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Central memory CD4+ T cells play a protective role against immune checkpoint inhibitor–associated myocarditis

Yu,

Long,

et al. 2024

Cardiovascular Research

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Aims The widespread use of immune checkpoint inhibitors (ICIs) has demonstrated significant survival benefits for cancer patients and also carry the risk of immune-related adverse events (irAEs). ICIs-associated myocarditis is a rare and serious adverse event with a high mortality rate. Here, we explored the mechanism underlying ICIs-associated myocarditis. Methods and results Using the peripheral blood of patients with ICIs therapy and ICIs treated mice with transplanted tumors, we dissect the immune cell subsets and inflammatory factors associated with myocarditis. Compared to the control group, patients with myocarditis after ICIs therapy showed an increase in NK cells and myeloid cells in peripheral blood, while T cells significantly decreased. Among T cells, there was an imbalance of CD4/CD8 ratio in the peripheral blood of myocarditis patients, with a significant decrease in central memory CD4+ T (CD4+ TCM) cells. RNA-Seq revealed that CD4+ TCM cells in myocarditis patients were an immunosuppressive cell subset, which highly express the immunosuppressive factor IL4I1. To elucidate the potential mechanism of the decrease in CD4+ TCM cells, protein array was performed and revealed that several inflammatory factors gradually increased with the severity of myocarditis in the myocarditis group, such as IL-1B/CXCL13/CXCL9, while the myocardial protective factor IL-15 decreased. Correlation analysis indicated a positive correlation between IL-15 and CD4+ TCM cells, with high expression of IL-15 receptor IL15RA. Furthermore, in vivo studies using an anti-PDL1 antibody in a mouse tumor model indicated a reduction in CD4+ TCM cells and an increase in CD8+ TEMRA cells, alongside evidence of cardiac fibrosis. Conversely, combining anti-PDL1 antibody treatment with IL-15 led to a resurgence of CD4+ TCM cells, a reduction in CD8+ TEMRA cells, and a mitigated risk of cardiac fibrosis. Conclusions Our data highlight CD4+ TCM cells as a crucial role in cardiac protection during ICIs therapy. IL-15, IL4I1 and CD4+ TCM cells can serve as therapeutic targets to reduce ICIs-associated myocarditis in cancer patients.

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Efficacy and safety of anti-programmed death-1 antibody-based combination therapy in advanced or metastatic gastric or gastroesophageal junction cancer in Chinese patients: A real-world study

Gao,

Li,

Qiu

et al. 2024

Science Progress

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Purpose: Programmed death-1 antibody plus chemotherapy has gained approval for the treatment for (human epidermal growth factor receptor 2 negative locally advanced or metastatic gastric or gastroesophageal junction cancer. This study aims to analyze the efficacy and safety of anti-programmed death-1 antibody combined with chemo- or anti-angiogenesis therapy in Chinese patients with advanced or metastatic gastric or gastroesophageal junction cancer in a real-world setting. Methods: In total, 122 patients treated with anti-programmed death-1 antibody-based combination therapy between April 2019 and December 2021 were encompassed. Clinical outcomes and safety proﬁle were measured and analyzed. Results: In the whole cohort, median overall survival was 17.2 months, median progression-free survival was 10.9 months, and median duration of response was 9.4 months. Notably, in the first-line patients, the median overall survival was not reached, median progression-free survival was 14.8 months, objective response rate was 68.4%. In the second-line group, median overall survival, median progression-free survival, median duration of response, and objective response rate were 10.9 months, 5.9 months, 4.5 months, and 41.5%, respectively. Treatment-related adverse events of any grade were observed in 28.2% of the overall cohort, primarily affecting the hematological and liver function. Grade 3 or 4 adverse events were mainly characterized by increased levels of aspartate aminotransferase, alanine aminotransferase, along with decreased lymphocyte and white blood cells, as well as anemia. Conclusions: Patients in our cohort experienced a clinical benefit from anti-programmed death-1 antibody-combined treatment in first-line treatment settings, with acceptable treatment-related adverse events. The benefit of anti-programmed death-1 antibody combined with chemo- or anti-angiogenesis treatment to the second-line patients should be further confirmed by large multi-center randomized, controlled clinical trials.

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Early evaluation of severe immune checkpoint inhibitor-associated myocarditis: a real-world clinical practice

Cited by 5 publications

References 30 publications

Early identification of severe immune checkpoint inhibitor associated myocarditis: From an electrocardiographic perspective

Early identification of severe immune checkpoint inhibitor associated myocarditis: From an electrocardiographic perspective

Central memory CD4+ T cells play a protective role against immune checkpoint inhibitor–associated myocarditis

Efficacy and safety of anti-programmed death-1 antibody-based combination therapy in advanced or metastatic gastric or gastroesophageal junction cancer in Chinese patients: A real-world study

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