Influence of adipose tissue distribution, sarcopenia, and nutritional status on clinical outcomes after CD19 CAR T-cell therapy.

Although CD19-directed chimeric antigen receptor T-cell therapy (CD19.CAR-T) has proven clinical efficacy for multiple refractory B-cell malignancies, over 50% of patients ultimately relapse. Recent evidence has underlined the critical role of the host in determining treatment responses. In this retrospective observational study of 106 relapsed/refractory large B-cell lymphoma (LBCL) patients receiving standard-of-care CD19.CAR-T, we analyzed the impact of immunometabolic host features and detailed body composition measurements on post-CAR-T clinical outcomes. We extracted muscle and adipose tissue distributions from pre-lymphodepletion CT images and assessed laboratory-based immuno-nutritional scores. Early responders displayed increased total abdominal adipose tissue deposits (TAT: 336 vs. 266 mm3, P=0.008) and favorable immuno-nutritional scores compared to non-responding patients. On univariate Cox regression analysis, visceral fat distribution, sarcopenia, and nutritional indices significantly impacted both progression-free (PFS) and overall survival (OS). Patients with a low skeletal muscle index (e.g. SMI<34.5), a sarcopenia indicator, exhibited poor clinical outcomes (mOS 3.0 vs. 17.6 months, log-rank p=0.0026). Prognostically adverse immuno-nutritional scores were linked to inferior survival (low PNI, HROS: 6.31, 95% CI: 3.35-11.90, P<0.001). In a multivariable analysis adjusting for baseline ECOG, CRP, and LDH, increased TAT independently associated with improved clinical outcomes (adjusted HROS: 0.27, 95% CI: 0.08-0.90, P=0.03). We noted particularly favorable treatment outcomes in patients with both increased abdominal fat and muscle mass (TAThigh/SMIhigh: 1-yr PFS 50%, 1-yr OS 83%). These real-world data provide evidence for a role of body composition and immuno-nutritional status in the context of CD19.CAR-T and suggest that the obesity paradox extends to modern T-cell based immunotherapies.