Effect of BMI on CAR T-cell therapy outcomes: Real-world analysis.

Abstract

e19013 Background: The escalating obesity rates in the USA are contributing to an increase in associated health complications. Limited data exists regarding obesity and its effects on CAR T-cell outcomes. Our study aimed to rigorously evaluate the real-world outcomes of patients undergoing CAR-T cell therapy based on their BMI. Methods: This multicenter, retrospective cohort analysis compared patients with normal BMI 18-25 kg/m² (Cohort 1 or C1) and patients with high BMI>25 kg/m² (Cohort 2 or C2) using BMI assessment before receiving CAR T-cell therapy, using TriNetX database. The outcomes were survival probability, rates of Cytokines Release Syndrome (CRS), Immune-effector Cells associated neurotoxicity syndrome (ICANS), and Infections. The outcomes were assessed by Kaplan-Meier analysis, hazard ratios, risk ratios, and 95% confidence intervals. Results: 4657 patients were analyzed (1606 in Cohort 1, 3051 in Cohort 2). Propensity score matching (PSM) was performed using forty-seven unique variables, including age, sex, ethnicity, labs, and comorbidities, to ensure comparability between the groups. After PSM, 1544 patients were identified in each cohort. After PSM analysis, the 3-year survival probability was significantly higher in the high BMI group (C1 vs C2: 55% vs 61%, p= <0.001). The rate of CRS (57.3% vs. 58.3%, p=0.56) and ICANS (21.3% vs. 19.8%, p= 0.30) were similar in C1 & C2 respectively. Different grades of CRS and ICANS were similar in both groups. The risk of infection was significantly lower in the high BMI group (C1 vs. C2: 56.2% vs. 52.1%, p=0.02), with a lower numerical rate of viral, fungal, and bacterial infection in the high BMI group. We evaluated weight loss at the end of the time window; 46.5% in C2 had BMI decreased to 18-25 kg/m², while 15% in C1 and 4.7% in C2 ended up with BMI <18 kg/m². The risk of heart failure (C1 vs. C2: 11.5% vs. 13.4%, p=0.05), Diabetes (C1 vs. C2: 16% vs. 26%, p= <0.001), & HTN (C1 vs C2: 39.5% vs. 52%, p= <0.001) was significantly higher in the high BMI group after CAR T-cell therapy. Conclusions: Our study is the most extensive and first study to date to evaluate the effects of BMI on CAR T-cell therapy outcomes, showing a protective effect of BMI in patients undergoing CAR T-cell therapy. Our study underscores the complex relationship between BMI and clinical outcomes following CAR T-cell therapy. It suggests that high BMI patients (>25 kg/m²) may have a survival advantage and lower infection risk, even though they face increased risks of specific comorbidities. Further research is warranted to elucidate the mechanisms underlying these observations and to optimize CAR T-cell therapy for patients with varying BMI profiles. BMI and CAR T-cell outcomes. Cohort 1 (BMI 18-25 kg/m²) Cohort 2 (BMI >25 kg/m²) P value Total # of pts 1544 1544 Survival Probability (%) 55 61 0.001 * Infection rate (%) 56.2 52.1 0.02 * CRS (%) 57.3 58.3 0.56 ICANS (%) 21.3 19.8 0.30 Weight loss to <18kg/m 2 BMI 15.0 4.7 <0.001 * *Statistically significant.