The impact of obesity and its related underlying diseases on cytokine release syndrome and the efficacy of CAR-T therapy in treating B-cell malignancies.

Chimeric Antigen Receptor T-cell (CAR-T) therapy has revolutionized treatment for relapsed/refractory B-cell malignancies, including B-cell Acute Lymphoblastic Leukemia (B-ALL) and Diffuse Large B-Cell Lymphoma (DLBCL). However, the influence of obesity and related comorbidities on treatment outcomes and toxicity profiles remains unclear. This retrospective study included 115 patients treated with CAR-T therapy at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from 2017 to October 2023. Patients were stratified into high-risk and low-risk groups based on Body Mass Index (BMI) and the presence of obesity-related comorbidities. Clinical outcomes, including Cytokine Release Syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) severity, treatment efficacy, Overall Survival (OS), and Progression-Free Survival (PFS), were analyzed. Logistic regression models assessed the relationships between covariates and clinical outcomes. The median BMI was 21.91 (IQR 19.265-24.365). Among the patients, 32 were overweight, and only one had a BMI over 30. Severe CRS occurred in 16 patients, with a higher proportion in those with obesity or related conditions (10.4% vs. 3.5%, p = 0.01). Hyperlipidemia significantly increased the risk of severe CRS (OR = 3.730, CI [1.204-11.556], p = 0.022). However, being overweight, having diabetes, hypertension, coronary heart disease, or fatty liver were not significantly associated with severe CRS. Elevated total cholesterol was moderately correlated with increased Interleukin 6 (IL-6) levels (R = 0.637, p < 0.001) and weakly with Interferon gamma (IFN-γ) (R = 0.337, p < 0.001). Besides, overweight patients had a lower proportion of CAR-T cells post-infusion (OR = 0.98, CI [0.961-1.0], p = 0.048). Obesity and related comorbidities did not significantly impact treatment efficacy. However, hyperlipidemia was associated with an increased risk of severe CRS, emphasizing the need for tailored risk management strategies in CAR-T therapy. Clinical trial: NCT02965092/ NCT03366350/ NCT04008251(ClinicalTrials.gov).