Immune Checkpoint Inhibitors

ABC

Original Article

Prognostic Value of Troponin to Lymphocyte Ratio in Patients with Immune Checkpoint Inhibitor-associated Myocarditis

Wanwen Chen et al. Wenhao Zhang Caiyin Luo Junying Cai … Xinqing Lin Chengzhi Zhou Yuwen He

Abstract

Background

Immune checkpoint inhibitor (ICI)-associated myocarditis is a rare but life-threatening immune-related adverse event (irAE). Cardiac troponin (cTn) and absolute lymphocyte count (ALC) have been reported to be associated with ICI-myocarditis.

Objective

We aimed to investigate the prognostic value of the combination of these two features (cTn/ALC ratio) in ICI-associated myocarditis.

Methods

Our center performed a retrospective analysis of 46 patients with ICI myocarditis (cases) and 46 patients without myocarditis after receiving ICI (controls). We obtained data on cardiac enzymes, routine blood parameters, and other clinical biomarkers. Statistical significance was defined as a two-sided α level of 0.05. The association between these covariates and the clinical outcomes of ICI-mediated myocarditis was also tested.

Results

Abnormally elevated cTn (p < 0.001), cTn/ALC ratio (p < 0.001), and decreased ALC (p < 0.001) were observed in patients who developed ICI-myocarditis. The cTn/ALC ratio was associated with the development of severe myocarditis (OR, 5.05; 95% CI, 1.22-20.84; p = 0.025). Survival analysis and Cox regression analysis indicated that a higher cTn/ALC ratio emerged as a significant independent predictor for major adverse cardiac events (MACE) [HR, 5.64; 95%CI, 1.43-22.34; p = 0.014].

Conclusions

An increase in the cTn/ALC ratio was associated with the severity of ICI-myocarditis and could be an effective predictor of poor prognosis in patients with ICI-associated myocarditis.

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ABCIC

Editorial

Metformin in Combination with Immune Checkpoint Inhibitors: Myocardial FDG Uptake Can Predict Prognosis?

Claudio Tinoco Mesquita et al. Ana Beatriz Couto Marina Schmid Nunes Fernanda Azevedo Silva

In Brazil, the estimate for 2023-2025 indicates that there will be 704,000 new cancer cases in the country, 221,000 of which will be non-melanoma skin cancers, cited as the most common type. After this type of cancer, breast cancer has the highest incidence, with 74,000 cases, followed by prostate cancer, with 72,000 cases, colorectum cancer, with 46,000 cases, and lung cancer, with 32,000 new cases. The cancer epidemiological profile in Brazil is like countries with a high income; however, it differs when analyzed by region, indicating significant regional inequalities. While in the country’s more developed regions (South and Southeast), the age-adjusted incidence rates range between 180 and 190 cases per 100,000 inhabitants, in less developed regions (North and Northeast), these rates vary from 157 to 164 cases per 100,000 inhabitants. The highest cancer mortality in Brazil is due to lung cancer (13.7% of cancer deaths), followed by colorectum cancer (10.4% of cancer deaths), and then breast cancer (8% of cancer deaths).

Immune checkpoints, like PD-1, PD-L1, and CTLA-4, regulate the immune system and help to equilibrate immune activation and suppression. They act by avoiding a strong immune response that could attack normal cells. Tumor cells can use these mechanisms to elude the immune system, decreasing its response. The mechanisms used for immune system evasion in lung cancer are linked to PD-1 inhibition, which reduces the activity of tumor immunity cells. Additionally, there is a decrease in T-lymphocyte proliferation and cytokine production (IL-2 and IFN-γ), allowing neoplastic cells to proliferate.

[…]

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ABCIC

Original Article

Variations in Myocardial FDG Uptake and Metformin Use: Implications for Survival during Immunotherapy

Matheus Coelho Torres et al. Juliana Goes Martins Fagundes Luís Fábio Barbosa Botelho Alinne Fernanda Amaral Verçosa Marcelo Dantas Tavares de Melo

Abstract

Background:

The rise of immune checkpoint inhibitors (ICIs) has significantly improved lung cancer outcomes; however, there is a lack of response prediction protocols. Furthermore, preclinical studies have indicated a promising association between metformin, β-blockers (BBs), and improved cancer patient outcomes.

Objectives:

The primary objective of this study was to investigate metformin’s impact on survival outcomes. The secondary objectives included assessing myocardial FDG uptake variation (change in standardized uptake value [ΔSUV]) during ICI treatment and evaluating the effects of smoking, diabetes, hypertension, and BB usage on survival outcomes.

Methods:

This single-arm, unicentric retrospective cohort study evaluated lung cancer patients who started using ICIs from July 2016 to December 2021. Inclusion criteria were age 18 years or above, lung cancer treated with ICIs (CTLA-4, PD-1, and PD-L1 inhibitors), and having undergone at least two positron emission tomography-computed tomography (PET-CT) scans.

Results:

Fifty-eight patients fulfilled all the inclusion criteria. Metformin users presented a 759-day increase in overall survival (OS) (p = 0.015). A trend of a 161-day increase in progression-free survival was observed in patients with positive myocardial ΔSUV compared to the negative ΔSUV group (p = 0.066), along with a trend of a 285-day increase in favor of BB users (p=0.886).

Conclusion:

The significant association between metformin use and increased OS suggests metformin as a promising adjuvant for ICI therapy. A trend of positive myocardial ΔSUV and improved outcomes may suggest a potential role of PET-CT in response prediction; however, larger studies are necessary to solidify this hypothesis.

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ABCHF

Viewpoint

Advances in Diagnosis and Treatment of Cancer Immunotherapy and CAR-T Cell–Related Myocarditis

Ariane Vieira Scarlatelli Macedo et al. Aurea Grippa Katia Regina Medeiros Luz Nathalia Coelho de Castro Nunes Sandrigo Mangini

Immune checkpoint inhibitors

The incidence of myocarditis in patients using ICI is low, around 1%. However, several series describe mortality between 30% and 40%. This is the primary reason that every effort is made for myocardial protection and early identification of signs of inflammatory response onset, in addition to understanding of T cell and macrophage stimulation and cytokine production.^, The onset of the lesion is most frequently observed observed early after the first dose of immunotherapy with a median time to onset of 30 days, with an average resolution of 90 to 120 days. Patients over 60 years of age are the most affected in the majority of series.

Patients with suspected ICI-associated myocarditis may develop from asymptomatic conditions with increased biomarkers to severe presentations including cardiogenic shock, ventricular arrhythmias, and sudden death. Dyspnea and asthenia are the most common complaints related to ICI-associated myocarditis; chest pain may also occur. The combination of ICI appears to be an important risk factor compared to monotherapy.

[…]

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ABCHF

Review Article

Myocarditis in Cancer Patients: A Review of an Emerging Problem in Cardio-Oncology

Wolney de Andrade Martins et al. Eduardo Schlabendorff

Abstract

Patients with cancer have a multitude of etiological factors for developing myocarditis. Classical or conventional chemotherapy, radiation therapy, and, more recently, immunotherapy have all been described as possible etiologies of myocarditis. Furthermore, patients with cancer are immunosuppressed and more susceptible to bacterial and viral infections that can cause myocarditis. This narrative review addresses the many possible causes of myocarditis in patients with cancer. Particular emphasis will be given to immune checkpoint inhibitor (ICI)-induced myocarditis. ICI myocarditis generally affects male patients, over the age of 50, who are being treated for lung cancer, melanoma, or renal cell carcinoma and have multiple comorbidities. Clinical manifestations present early, with elevated troponin and electrocardiogram changes. The case fatality rate is high. Treatment consists of discontinuation of the offending ICI and corticosteroid therapy. Myocarditis due to cyclophosphamide, anthracyclines, 5-fluorouracil, cisplatin, carboplatin, proteasome inhibitors, immunomodulators, tyrosine kinase inhibitors, and radiation therapy will also be addressed.

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Prognostic Value of Troponin to Lymphocyte Ratio in Patients with Immune Checkpoint Inhibitor-associated Myocarditis

Abstract

Background

Objective

Methods

Results

Conclusions

Metformin in Combination with Immune Checkpoint Inhibitors: Myocardial FDG Uptake Can Predict Prognosis?

Variations in Myocardial FDG Uptake and Metformin Use: Implications for Survival during Immunotherapy

Abstract

Background:

Objectives:

Methods:

Results:

Conclusion:

Advances in Diagnosis and Treatment of Cancer Immunotherapy and CAR-T Cell–Related Myocarditis

Immune checkpoint inhibitors

Myocarditis in Cancer Patients: A Review of an Emerging Problem in Cardio-Oncology

Abstract

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