Predictors of response to CD19 chimeric antigen receptor T-cell therapy in large B-cell lymphoma: a consolidated review.

Abstract

Purpose of review: CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has transformed outcomes for relapsed/refractory large B-cell lymphoma (LBCL), yet nearly half of treated patients relapse, and toxicities remain frequent. A deeper understanding of response predictors is urgently needed to guide patient selection, treatment optimization, and development of rational combination strategies.

Recent findings: Emerging data reveal that response to CAR-T therapy is shaped by patient-specific, tumor-intrinsic, and treatment-related factors. Clinical variables such as age, performance status, inflammation, and microbiome composition influence efficacy. Tumor burden, disease distribution, histologic subtype, and genomic alterations correlate with resistance. Treatment factors, including bridging strategies, lymphodepletion regimen, and CAR-T product design, affect expansion, persistence, and clinical outcomes. Novel insights from immune profiling, radiomics, and single-cell transcriptomics offer further granularity and predictive potential.

Summary: Predictors of CAR-T response span diverse biological and clinical domains and are increasingly actionable. Integrating multimodal biomarkers into routine workflows can personalize care and improve outcomes. Prospective validation, real-time monitoring, and adaptive trial designs are essential next steps toward precision CAR-T therapy.