Factors Associated with Increased Risk of Major Cardiovascular Events for Patients Undergoing CAR T Therapy

Abstract

Introduction: Chimeric antigen receptor (CAR)-T cell therapy use has increased exponentially following its approval for multiple indications in non-Hodgkin lymphomas, multiple myeloma, and acute lymphoblastic leukemia. While cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias are well-described and frequently encountered side effects, a significant proportion of patients experience major adverse cardiovascular events (MACE). This study investigates factors associated with increased risk for MACE. Methods: We performed a retrospective analysis of a consecutive cohort of patients treated with CAR-T therapy at our center between 2018 and 2022. Clinical, laboratory, and imaging parameters were collected. MACE were defined as acute myocardial infarction (AMI), stroke or transient ischemic attack, cardiovascular death, unstable angina, life-threatening arrhythmias, and heart failures. Data was analyzed using SPSS v23. Categorical variables were compared using univariate chi-square test. Results: A total of 126 patients were included. Of these, ten patients (12.5%) had a MACE event. Baseline characteristics including age, sex, body mass index, coronary artery calcium, lipid profile, baseline medications, preceding anthracycline or carfilzomib exposure, cancer type, CRS, ICANS, and tocilizumab use are summarized in Table. The median follow-up period was 8.9 months. Patients who experienced MACE versus no MACE had a significantly higher age at CAR-T cell therapy (74.5 years vs. 64.9 years, p = .009), higher peak C-reactive protein (CRP) with a median of 116.7 mg/dL versus 73.85 mg/dL, p = 0.006 respectively. CRS and ICANS grades were associated with MACE events (p = 0.008 and 0.005, respectively). No echocardiographic differences were found. No progression free or overall survival differences were observed in the groups (p = 0.67 and 0.16, respectively). Conclusions: Our results indicate that patients undergoing CAR-T cell therapy who are older and who experience an increased degree of inflammatory response, reflected by peak CRP level, were associated with MACE. These data suggest that inflammatory markers may be clinically relevant predictors of subsequent MACE in CAR-T therapy-treated patients. Prospective inflammation monitoring combined with trials incorporating anti-inflammatory strategies may mitigate the risk of MACE in this patient population. Keywords: Cellular therapies, Diagnostic and Prognostic Biomarkers, Molecular Targeted Therapies Conflicts of interests pertinent to the abstract. G. Kaur Consultant or advisory role: SANOFI, BMS, Janssen, Cellectar, Arcellx Y. F. Madanat Consultant or advisory role: BluePrint Medicines, GERON, OncLive, MD Education, Sierra Oncology, Stemline Therapeutics, Blueprint Medicines, Morphosys, Taiho Oncology and Novartis Honoraria: BluePrint Medicines, GERON, OncLive, MD Education, Sierra Oncology, Stemline Therapeutics, Blueprint Medicines, Morphosys, Taiho Oncology and Novartis Educational grants: Blueprint Medicines and Morphosys.