The role of obesity on outcomes of adoptive cellular therapy in solid tumors.

2544 Background: Anti-tumor response and toxicity outcomes with adoptive cell therapy (ACT) have been heterogeneous in solid tumors, and it is still unclear how host factors such as obesity may contribute to efficacy and immune-related safety events. Methods: We conducted a retrospective study including 95 consecutive advanced solid tumor patients who received ACT on protocol in the Department of Investigational Cancer Therapeutics between August 2017 and June 2023. We analyzed baseline clinical characteristics, immune-related safety events, response to ACT, and survival outcomes between obese and non-obese patients. Overweight was defined as body mass index (BMI) 25-29.99 kg/m 2 and obesity was defined as BMI ≥ 30 kg/m 2 at the time of treatment. Fisher’s exact test was used to compare the proportions of categorical variables between two groups. Pairwise comparison with Bonferroni correction was performed if necessary. T-test was used to compare the mean of continuous variables between two groups. The distributions of overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier method. Log-rank test was used to compare the distributions of OS and PFS by baseline characteristics. Hazard ratio was estimated in Cox proportional hazard regression model. A two-sided p-value < 0.05 was considered statistically significant. Results: The median age at treatment was 60.9 (range 20.5 – 84). Thirty-nine patients (41.1%) had a BMI (kg/m 2 ) defined as normal weight, 26 (27.4%) as overweight, 27 (28.4%) as obese, and 3 (3.2%) as underweight. Eighty-four (88.4%) were Caucasian; 54 (56.8%) were female. The most prevalent cancers were gastrointestinal (21.1%), gynecologic (15.8%), sarcoma (11.6%), mesothelioma (10.5%), breast (8.4%). The median follow-up was 39.9 months, with a median PFS of 2.8 months (95% CI: 2.3, 3.5) and a median OS of 8.4 months (95% CI: 6.4, 11.0). The risk of death among the obese patients was 0.56 (95% CI: 0.31, 0.99) times the risk of death among normal weight patients (p = 0.045). No weight difference was found between responder and non-responder. While BMI was not associated with the development of cytokine release syndrome (CRS), the patients with normal weight had a higher proportion of immune effector cell-associated neurotoxicity syndrome (ICANS) than the obese patients (23.1% vs 0%, p = 0.049). Conclusions: Obesity was associated with improved survival and decreased ICANS rates following ACT. Our findings may suggest a differential interaction between obesity, different immunotherapeutic modalities, and hematologic vs nonhematologic cancers.