脂肪组织分布、肌少症与营养状态对 CD19 CAR-T 细胞治疗后临床结局的影响

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 patients with relapsed/refractory large B-cell lymphoma 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 prelymphodepletion CT images and assessed laboratory-based immuno-nutritional scores. Early responders displayed increased total abdominal adipose tissue deposits (TAT: 336 mm3 vs. 266 mm3, P = 0. 008) and favorable immuno-nutritional scores compared to nonresponding 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 (SMI; e. g.

<34. 5), a sarcopenia indicator, exhibited poor clinical outcomes (mOS 3. 0 months 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% confidence interval (CI), 3. 35-11. 90; P < 0. 001].

In a multivariable analysis adjusting for baseline Eastern Cooperative Oncology Group performance status, C-reactive protein, and lactate dehydrogenase, increased TAT was 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-year PFS 50%, 1-year 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 may extend to modern T cell-based immunotherapies. See related Spotlight by Nawas and Scordo, p. 704.