The Impact of Cardiovascular Vulnerabilities in Non Hodgkin Lymphoma Patients Treated with Chimeric Antigen Receptor T Cell Therapy

INTRODUCTION: CAR-T therapy is an effective treatment for hematological malignancies. However, in recent years there is a growing body of literature suggesting adverse cardiovascular (CV) events among patients treated with CAR-T therapy. Whether cardiovascular risk factors serve as determinants of CV complications and CAR-T outcomes is unclear. The aim of this study is to investigate the landscape and prognostic role of CV comorbidities in patients with non-Hodgkin lymphoma (NHL) treated with autologous CD19- CAR-T. METHODS: We included patients with NHL treated with CD19-directed CAR-T across two tertiary care centers. Data collected included baseline demographics, CV risk factors, and outcomes. CV disease and risk factors included were: coronary artery disease (CAD), diabetes, hypertension (HTN), sleep apnea, smoking history, and stroke/ transient ischemic attack (TIA). CV events were defined as atrial fibrillation (AF), heart failure (HF), acute coronary syndrome (ACS), and cardiogenic shock. All CV events were adjudicated by a board certified cardiologist. RESULTS: In the cohort of 345 patients, 87% had large B cell lymphoma (LBCL), 4% follicular lymphoma, and 9% mantle cell lymphoma (MCL). Predominant CV vulnerabilities included a history of smoking (41%), HTN (32%), diabetes (12%), sleep apnea (8%), history of CAD (7%), and history of stroke/TIA (5%). Patients were categorized based on number of CV risk factors or CV disease with 37% having 0, 35% with 1, and 28% with 2 or more. A total of 41 (12%) patients experienced a CV event within the first 100 days after CAR-T infusion, with 29 (8.4%) patients developing AF, 15 (4.3%) patients with HF, 2 (0.5%) patients with ACS, and 2 (0.5%) patients with cardiogenic shock. Five patients experienced more than one cardiac event. Univariable logistic regression of CV vulnerabilities revealed that patients with a history of HTN (OR 2.23, 95% CI 1.15-4.33, p = 0.018), 1 CV risk factor (OR 2.57, 95% CI 1.05-6.91) and/or 2 or more CV risk factors (OR 3.67, 95% CI 1.51-9.88) were associated with an increased risk of CV event(s) (global p=0.012). Additional baseline characteristics increasing risk of CV events included older age (OR 1.04, 95% CI: 1.01 - 1.07, p = 0.004), Karnofsky performance scale < 90 (OR 2.31, 95% CI: 1.13-5.12, p = 0.021), or stage III-IV disease (OR 2.90, 95% CI 1.11-9.94, p = 0.028). The 1-year overall survival was 62%, with a trend towards worse overall survival (HR 1.59, 95% CI:1.0-2.54, p=0.