Immune checkpoint inhibitors (ICIs) are revolutionizing cancer treatment, but they can also cause serious cardiac complications known as ICI-related cardiotoxicity (ICICT). Researchers from Chongqing Medical University in China have developed a novel risk assessment strategy that could help identify patients at high risk of ICICT before starting immunotherapy. The study found that four common clinical biomarkers – cardiac troponin T (cTnT), high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and coronary artery calcium (CAC) score – are all independently associated with an increased risk of ICICT. By combining these four biomarkers into a simple scoring system, the researchers were able to stratify patients into low, medium, high, and very high-risk categories for developing severe cardiac complications like cardiomyopathy, myocarditis, heart failure, and even death. This multimodal approach provides a practical tool for clinicians to assess cardiac risk and implement preventive measures for cancer patients before starting ICI treatment. Immune checkpoint inhibitors, Cardiotoxicity, Biomarkers, Risk assessment, Cancer treatment
Understanding the Cardiac Risks of Immunotherapy
The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, leading to significant improvements in tumor regression and long-term survival for many patients. However, these revolutionary therapies also come with a concerning side effect – an increased risk of ICI-related cardiotoxicity (ICICT). ICICT can manifest in various forms, including cardiomyopathy, myocarditis, heart failure, arrhythmias, and even stroke. These cardiac complications can be severe, with mortality rates as high as 50% in some cases.
Recognizing the urgent need to address this issue, researchers from the First Affiliated Hospital of Chongqing Medical University in China set out to develop a more effective way to assess the risk of ICICT before starting immunotherapy. Their goal was to create a practical, multimodal scoring system that could help clinicians identify high-risk patients and implement appropriate preventive measures.
Identifying Key Biomarkers for ICICT
The research team focused on four common clinical biomarkers that have shown promise in predicting cardiovascular risks in other settings: cardiac troponin T (cTnT), high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and coronary artery calcium (CAC) score.
Cardiac troponin T is a well-established marker of myocardial injury, while hs-CRP and NT-proBNP indicate inflammation and neurohormonal activation, respectively. The CAC score, derived from non-contrast CT scans, provides a measure of subclinical atherosclerosis.
Table 1 Multivariable-adjusted ICICT risk of four biomarker results.
Through a retrospective analysis of 375 cancer patients undergoing immunotherapy, the researchers found that all four of these biomarkers, when measured before starting ICI treatment, were independently associated with a higher risk of developing ICICT. This was true across a broad spectrum of cardiac complications, including cardiomyopathy, myocarditis, heart failure, myocardial infarction, stroke, and even death.
Developing a Multimodal Risk Scoring System
Building on these findings, the research team created a simple, integer-based risk scoring system that combined the four biomarkers. Patients were assigned one point for each abnormal biomarker result, resulting in a score ranging from 0 to 4.
Fig. 2
The researchers found that this multimodal scoring approach provided much stronger risk stratification than any single biomarker alone. Compared to patients with a low-risk score (0-1), those with a “very high-risk” score of 4 had a 7- to 9-fold higher risk of developing severe ICICT, even after accounting for other potential confounding factors.
Implications and Future Directions
This study represents a significant step forward in addressing the growing challenge of ICICT. By combining four readily available, inexpensive biomarkers into a simple risk assessment tool, clinicians can now more effectively identify cancer patients who may require closer monitoring and early preventive interventions before starting immunotherapy.
The findings also highlight the importance of considering a broader spectrum of cardiovascular complications beyond just cardiomyopathy and myocarditis when evaluating the cardiac risks of ICIs. The researchers’ attention to other severe outcomes like stroke and arrhythmias provides a more comprehensive understanding of the cardiovascular impact of these therapies.
As the use of ICIs continues to expand, this multimodal risk scoring system could become an invaluable resource for oncologists and cardiologists, helping to ensure the safe and effective use of these transformative cancer treatments. Future research may explore the utility of this approach in other cancer populations and investigate whether dynamic changes in biomarker levels during ICI treatment can further refine risk assessment.
Author credit: This article is based on research by Zhulu Chen, Rui Lan, Tao Ran, Li Tao, Yuxi Zhu, Yanwei Li, Chuan Zhang, Min Mao, Diansa Gao, Zhong Zuo.
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