Background: Previous retrospective studies have shown that chimeric antigen receptor T (CAR-T) cell therapy may be associated with major adverse cardiovascular events (MACE), especially in the context of cytokine-release syndrome (CRS) events.
Objectives: The aim of this prospective observational study was to define the occurrence of MACE in adults undergoing treatment with CAR-T cell therapy and identify associated risk factors.
Methods: Vital signs, blood samples, and an echocardiogram were collected prior to and 2 days, 1 week, 1 month, and 6 months after CAR-T cell infusion, and charts were consulted at 12 months. In the event of CRS, echocardiography was repeated within 72 hours. MACE were defined as cardiovascular death, symptomatic heart failure, acute coronary syndrome, ischemic stroke, and de novo cardiac arrhythmia.
Results: A total of 44 patients were enrolled (mean age 58 ± 11 years, 77% men). The median follow-up duration was 487 days (Q1-Q3: 258-622 days). There were 24 episodes of CRS in 23 patients (52%) (13 grade 1, 10 grade 2, and 1 grade 3), with a median time to CRS of 4 days. Two patients had MACE (heart failure with preserved ejection fraction and atrial fibrillation) within 1 year and 6 and 7 days after CAR-T cell infusion. There was no change in left ventricular ejection fraction, but a modest decrease in global longitudinal strain was noted.
Conclusions: There were few cardiac effects associated with contemporary CAR-T cell therapy. As MACE occurred after CRS episodes, aggressive treatment and close follow-up during CRS events are essential.
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http://dx.doi.org/10.1016/j.jaccao.2023.07.009 | DOI Listing |
Blood Rev
January 2025
Department of Hematology, First Hospital of Jilin University, Changchun, Jilin, China. Electronic address:
Multiple myeloma (MM) remains incurable and patients eventually face the relapse/refractory dilemma. B cell maturation antigen (BCMA)-targeted immunotherapeutic approaches have shown great effectiveness in patients with relapsed/refractory MM, mainly including chimeric antigen receptor T cells (CAR-T), bispecific T cell engagers (TCEs), and antibody-drug conjugates (ADCs). However, their impact on long-term survival remains to be determined.
View Article and Find Full Text PDFMol Ther
January 2025
Leibniz Institute for Immunotherapy (LIT), Division of Genetic Immunotherapy, Regensburg, Germany. Electronic address:
A rapidly growing number of chimeric antigen receptors (CARs) is being translated into cell therapy for malignant and autoimmune diseases. While cancer cell-selective CAR targeting is undergoing continuous refinement, specific testing for overlooked recognition of healthy tissues is commonly not performed, which potentially results in underestimating of the risk of severe tissue damage upon CAR T cell application. Using the FcμR/IgM receptor/FAIM3/TOSO-specific CAR, designed to target chronic lymphocytic leukemia cells, we exemplarily outline a screen to uncover reactivities to healthy tissues and discuss the value of such pre-clinical testing to improve safety in CAR T cell application.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
TriArm Therapeutics, Niudun Road 200, 201203 Shanghai, China. Electronic address:
Background: The immunosuppressive microenvironment negatively affects the efficacy of chimeric antigen receptor T (CAR-T) cells in solid tumors. Fusion protein that combining extracellular domain of inhibitory checkpoint protein and the cytoplasmic domain of stimulatory molecule may improve the efficacy of CAR-T cells by reversing the suppressive signals.
Methods: To generate optimal PD1-TLR10 fusion proteins, PD1 extracellular domain and TLR10 intracellular domain were connected by transmembrane domain from PD1, CD28, or TLR10, respectively.
Biomarkers
January 2025
Pediatric Intensive Care Unit, Hospital Sant Joan de Déu-University of Barcelona, Barcelona, Spain.
PurposeChimeric antigen receptor (CAR) T-cell CD19 therapy has changed the treatment paradigm for patients with relapsed/refractory B-cell acute lymphoblastic leukemia. It is frequently associated with potentially severe toxicities: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and admission to PICU is often required. Some biomarkers seem to correlate with CRS severity.
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