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Biomarkers and CV Outcomes in CAR-T Therapy Recipients
Quick Takes
- This multicenter registry-based study investigated the association between severe cardiovascular events (SCEs) and mortality in patients undergoing anti-CD19 CAR-T chimeric antigen receptor T-cell (CAR-T) therapy.
- Patients who experienced SCEs had significantly higher overall mortality and nonrelapse mortality, as well as elevated peak levels of IL-6, CRP, ferritin, and troponin. SCEs were independently associated with increased mortality.
- These findings underscore the critical need for vigilant cardiovascular monitoring and management in patients undergoing CAR-T therapy, as the occurrence of SCEs may significantly impact patient outcomes, potentially informing therapeutic strategies and patient counseling in this rapidly evolving field of oncology.
Study Questions:
In patients receiving anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy, how does the occurrence of severe cardiovascular events (SCEs) compare to no occurrence of such events in terms of overall mortality, nonrelapse mortality, and peak levels of interleukin (IL)-6, C-reactive protein (CRP), ferritin, and troponin?
Methods:
This is a multicenter registry-based study of 202 recipients of anti-CD19 CAR-T (Chimeric Antigen Receptor T-cell) therapy examining the difference in clinical characteristics, outcomes, and biomarkers of patients who had a SCE and those who did not. SCE was defined as a composite of heart failure, cardiogenic shock, or myocardial infarction. The primary outcome of the study was overall mortality, with secondary outcomes including nonrelapse mortality and peak levels of specific biomarkers, namely IL-6, CRP, ferritin, and troponin.
Results:
The analysis included 202 recipients of CAR-T therapy, with a median age of 60 years, of which 16% of patients experienced a SCE at a median of 12 days after CAR-T cell infusion. Patients with SCE had a higher burden of pre-existing cardiovascular risk factors such as hypertension and a history of atrial fibrillation or heart failure. Baseline biomarkers prior to CAR-T infusion were available for a subset of patients, and those who experienced SCE had a greater median rise in troponin from baseline. Post-CAR-T infusion, SCE was associated with higher peak levels of inflammatory and cardiac biomarkers. Over a median follow-up of 297 days, 53% of patients died, with 86 deaths due to cancer recurrence or progression and 22 due to nonrelapse mortality. SCEs were more common among those who died, including a higher incidence of myocardial infarction and cardiogenic shock. The occurrence of SCE following CAR-T was independently associated with an increased risk of overall hazard ratio (HR) of 2.8 (95% confidence interval [CI], 1.6-4.7) and nonrelapse mortality of HR of 3.5 (95% CI, 1.4–8.8).
Conclusions:
Patients undergoing CAR-T therapy who experience SCEs have significantly higher overall and nonrelapse mortality, as well as elevated peak levels of troponin and inflammatory biomarkers.
Perspective:
This study provides crucial insights into the cardiovascular implications of CD19 targeting CAR-T therapy, an oncological treatment that is rapidly expanding in its applications. SCEs were associated with worse longer-terms outcomes and linked to higher peak levels of inflammatory and cardiac biomarkers such as IL-6, CRP, ferritin, and troponin. While long-term cardiovascular mortality was not defined, the findings suggest that the severe inflammation induced by CAR-T therapy may lead to long-term cardiotoxicity. The findings are particularly important given the increasing use of CAR-T therapy. The authors rightfully call for the development of standardized cardiovascular surveillance protocols for early detection of cardiotoxicity, similar to those established for other cancer therapies. Future investigations should also explore potential treatment options to mitigate CAR-T cardiotoxicity, such as the early use of tocilizumab, an IL-6 receptor antagonist, and traditional cardioprotective therapies.
Clinical Topics: Arrhythmias and Clinical EP, Cardio-Oncology, Dyslipidemia, Heart Failure and Cardiomyopathies, Atrial Fibrillation/Supraventricular Arrhythmias, Lipid Metabolism, Acute Heart Failure, Heart Failure and Cardiac Biomarkers
Keywords: Antigens, CD19, Atrial Fibrillation, Biomarkers, Cardiotoxicity, Cell- and Tissue-Based Therapy, C-Reactive Protein, Ferritins, Heart Failure, Interleukin-6, Myocardial Infarction, Receptors, Chimeric Antigen, Risk Factors, Shock, Cardiogenic, T-Lymphocytes, Troponin
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