Pretreatment TyG-BMI predicts CD19 CAR-T persistence and prognosis in diffuse large B-cell lymphoma

Abstract

Background Although CD19 CAR-T cell therapy has improved outcomes in relapsed or refractory diffuse large B-cell lymphoma (DLBCL), responses are variable and predictive biomarkers are lacking. The triglyceride glucose-body mass index (TyG-BMI)—a surrogate of insulin resistance—has shown prognostic value in solid tumors, but its relevance to DLBCL and CAR-T efficacy remains unknown. Methods We retrospectively analyzed 204 newly diagnosed DLBCL patients treated with rituximab-containing regimens, stratified by median TyG-BMI. Prognostic associations were assessed by Kaplan-Meier and multivariate Cox regression, and a nomogram was constructed. In an exploratory sub-analysis, 20 patients who received CD19 CAR-T therapy were assessed. CAR-T cell persistence was measured by flow cytometry one week post-infusion and correlated with pre-infusion TyG-BMI by Pearson analysis. CRS and ICANS were graded per ASTCT criteria. Post-CAR-T survival was compared by Kaplan-Meier analysis stratified by median pre-infusion TyG-BMI. Results High TyG-BMI was independently associated with poorer PFS (HR, 2.146; 95% CI, 1.092–4.214; P = 0.027) and OS (HR, 2.531; 95% CI, 1.084–5.913; P = 0.032), and further stratified risk within IPI risk groups and across disease stages. A nomogram incorporating TyG-BMI, IPI, and bone marrow involvement predicted 1-, 3-, and 5-year OS (AUC: 0.886, 0.799, 0.772). In the CAR-T subcohort (n = 20), elevated pre-infusion TyG-BMI was significantly inversely correlated with CAR-T cell persistence at one week post-infusion (r = -0.570, P = 0.009). Patients with high pre-infusion TyG-BMI experienced inferior responses to CAR-T therapy, with shorter median PFS (5.0 vs. 19.5 months) and OS (39.0 vs. 81.0 months) compared with the low TyG-BMI group. Conclusion TyG-BMI is an independent prognostic factor in DLBCL that refines IPI-based stratification, and elevated pre-infusion TyG-BMI is associated with attenuated CAR-T cell persistence and inferior outcomes. This readily available metabolic index may aid risk assessment and treatment planning in DLBCL.