A retrospective analysis of cardiovascular adverse events associated with immune checkpoint inhibitors
Jessica Castrillon Lal1,2, Sherry-Ann Brown3, Patrick Collier2,4
1Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Background:
Modern therapies in oncology have increased cancer survivorship, as well as the incidence of cardiovascular adverse events. While immune checkpoint inhibitors have shown significant clinical impact in several cancer types, the incidence of immune-related cardiovascular (CV) adverse events poses an additional health concern and has been reported.
Methods:
We performed a retrospective analysis of the FDA Adverse Event Reporting System data of suspect product reports for immunotherapy and classical chemotherapy from January 2010-March 2020. We identified 90,740 total adverse event reports related to immune checkpoint inhibitors and classical chemotherapy.
Results:
We found that myocarditis was significantly associated with patients receiving anti-program cell death protein 1 (PD-1) or anti-program death ligand 1 (PD-L1), odds ratio (OR) = 23.86 (95% confidence interval [CI] 11.76-48.42, (adjusted p-value) q < 0.001), and combination immunotherapy, OR = 7.29 (95% CI 1.03-51.89, q = 0.047). Heart failure was significantly associated in chemotherapy compared to PD-(L)1, OR = 0.50 (95% CI 0.37-0.69, q < 0.001), CTLA4, OR = 0.08 (95% CI 0.03-0.20, q < 0.001), and combination immunotherapy, OR = 0.25 (95% CI 0.13-0.48, q < 0.001). Additionally, we observe a sex-specificity towards males in cardiac adverse reports for arrhythmias, OR = 0.81 (95% CI 0.75-0.87, q < 0.001), coronary artery disease, 0.63 (95% CI 0.53-0.76, q < 0.001), myocardial infarction, OR = 0.60 (95% CI 0.53-0.67, q < 0.001), myocarditis, OR = 0.59 (95% CI 0.47-0.75, q < 0.001) and pericarditis, OR = 0.5 (95% CI 0.35-0.73, q < 0.001).
Conclusion:
Our study provides the current risk estimates of cardiac adverse events in patients treated with immunotherapy compared to conventional chemotherapy. Understanding the clinical risk factors that predispose immunotherapy-treated cancer patients to often fatal CV adverse events will be crucial in Cardio-Oncology management.
Insights
Immune checkpoint inhibitors significantly increase myocarditis risk, while chemotherapy is linked to heart failure. Understanding these risks is vital for managing cardiovascular events in cancer patients.
Area of Science:
- Cardio-Oncology
- Immunotherapy
- Oncology
Background:
- Cancer survivorship has increased due to modern therapies.
- However, cancer treatments, particularly immune checkpoint inhibitors, are associated with cardiovascular adverse events.
- Immune-related cardiovascular events are a growing concern in cancer care.
Purpose of the Study:
- To compare the risk of cardiac adverse events between immunotherapy and conventional chemotherapy.
- To provide current risk estimates for cardiovascular events in patients receiving different cancer treatments.
Main Methods:
- Retrospective analysis of FDA Adverse Event Reporting System data.
- Examined suspect product reports for immunotherapy and classical chemotherapy from January 2010 to March 2020.
- Identified 90,740 adverse event reports related to immune checkpoint inhibitors and chemotherapy.
Main Results:
- Myocarditis was significantly associated with anti-program cell death protein 1 (PD-1) or anti-program death ligand 1 (PD-L1) and combination immunotherapy.
- Heart failure showed significant association with chemotherapy compared to PD-(L)1, CTLA4, and combination immunotherapy.
- Cardiac adverse reports for arrhythmias, coronary artery disease, myocardial infarction, myocarditis, and pericarditis showed sex-specificity towards males.
Conclusions:
- This study offers current risk estimates for cardiac adverse events in patients treated with immunotherapy versus conventional chemotherapy.
- Identifying clinical risk factors for fatal cardiovascular adverse events in immunotherapy-treated patients is crucial for effective Cardio-Oncology management.
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