An Analysis of Cardiac Disorders Associated With Chimeric Antigen Receptor T Cell Therapy in 126 Patients: A Single-Centre Retrospective Study

Abstract

IntroductionChimeric antigen receptor T (CAR-T) cells are effective in treating hematological malignancies. However, in patients receiving CAR-T therapy, data characterizing cardiac disorders are limited.Methods126 patients with hematologic malignancies receiving CAR-T cell therapy were analyzed to determine the impact of CAR-T therapy on occurrence of cardiac disorders, including heart failure, arrhythmias, myocardial infarction, which were defined by the Common Terminology Criteria for Adverse Events (CTCAE). Parameters related to cardiac disorders were detected including myocardial enzyme, NT-proBNP and ejection fraction (EF). Cardiovascular (CV) events included decompensated heart failure (HF), clinically significant arrhythmias and CV death.ResultsThe median age of patients was 56 years (6 to 72 years). 58% patients were male, 62% had multiple myeloma, 20% had lymphoma and 18% had ALL. 33 (26%) patients had cardiac disorders, most of which were grade 1-2. 13 patients (10%) were observed with cardiac disorders grade 3-5, which comprised 5(4%) patients with new-onset HF, 2 (2%) patients with new-onset arrhythmias, 4 (3%) patients with the acute coronary syndrome, 1(1%) patient with myocardial infarction and 1(1%) patient with left ventricular systolic dysfunction. There were 9 CV events (7%) including 6 decompensated heart failure, 1 clinically significant arrhythmias and 2 CV deaths. Among the 33 patients with cardiac disorders, the patients with cardiac disorders CTCAE grade 3-5 had higher grade CRS (grade ≥ 3) than those with cardiac disorders CTCAE grade ≤ 2 (P <0.001). More patients with cardiac disorders CTCAE grade 3-5 were observed in the cohort who did not receive corticosteroids and/or tocilizumab therapy timely comparing with those who received corticosteroids and/or tocilizumab therapy timely (P =0.0004).ConclusionsCardiac disorders CAR-T cell therapy were common and associated with occurrence of CRS. However, most cases were mild. For patients with CRS grade 3-5, timely administration of corticosteroids and/or tocilizumab can effectively prevent the occurrence and progression of cardiac disorders.

Secretory co-factors in next-generation cellular therapies for cancer

“…After IL-1 overproduction, the monocytes/macrophages produce IL-6, which plays a pivotal role in CRS ( 50 ). Current clinical protocols to treat CRS include glucocorticoids and/or IL-6 blockade (tocilizumab) ( 1 , 52 ), whereas preemptive or early intervention with tocilizumab has been reported to prevent severe CRS ( 53 , 54 ). IL-1 blockade (anakinra) is another promising strategy that is currently in clinical trials ( 55 ).…”

Serious adverse events and coping strategies of CAR-T cells in the treatment of malignant tumors

“…The patient's symptoms improved quickly and the lung inflammation gradually subsided. Besides, K. Qi et al (125) analyzed the adverse events after treatment in 126 patients with hematologic malignancies who received CAR-T cells therapy. The results showed that cardiac adverse events associated with CAR-T cells therapy were common and related to the development of CRS.…”

Successful administration of CD19 chimeric antigen receptor T cells in association with severe cyanotic congenital heart disease

“…11 A key approach to improving outcomes is to reduce the risk of CRS and cardiac toxicity by pre-CD19-CART reduction of leukemia burden and a preemptive approach to treating CRS. 10,12 This case demonstrates that even in a pediatric patient with complex cyanotic heart disease, CD19-CART therapy could be tolerated and is a viable option to treat high-risk or relapsed B-ALL. However, the efficacy and safety of this approach need further study.…”