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 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.

Metastatic Calcinosis of Gastric Mucosa.

Calcinosis cutis refers to the deposition of calcium salts in the cutaneous and subcutaneous tissue and is frequently associated with inflammation. Gastric calcinosis can be classified into metastatic, dystrophic, and idiopathic; metastatic calcinosis is the most common type. In metastatic calcification, calcium salts are deposited in normal soft tissues in the setting of altered metabolism of serum calcium and phosphorus and is a rare and serious complication of chronic renal failure. The important factors contributing to the development of metastatic calcinosis are hypercalcemia, hyperphosphatemia, and an elevated calcium-phosphate product. The most striking feature of this diagnosis is the calcification around the large joints. While it mostly involves dermis of small and medium-sized vessels, it can rarely affect the mucosal layers of the gastrointestinal (GI) tract. Calcinosis presents as a marker for the presence of calcifications in other organs, such as heart or lung, which can be life-threatening. Patients rarely present with clinical symptoms of GI upset, dyspepsia, or epigastric pain that are attributed to calcinosis. If patients present with GI symptoms, infectious causes remain to be higher on the differential. We present a case of incidental finding of gastric mucosal calcinosis during the workup and treatment of dysphagia.