Prognostic factors and response monitoring after CD19-directed CAR T-cell therapy in diffuse large B-cell lymphoma: a time-resolved review

CD19-directed chimeric antigen receptor (CAR) T-cell therapy produces durable remission in a subset of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Outcomes vary with disease burden, host reserve, cellular product characteristics and the course of treatment. Interpretation of the biomarker literature is complicated by heterogeneous products, sampling windows, endpoints and mixed large B-cell lymphoma (LBCL) populations. This critical narrative review organizes the evidence by assessment time, biomarker role and validation design. Pretreatment burden, inflammation and host reserve provide prognostic information within treated populations. Apheresis and product characteristics inform hypotheses about cellular fitness, while bridging response updates the disease state before infusion. After treatment, cellular kinetics, tumor-specific circulating DNA and positron-emission tomography provide distinct measures of exposure and response. Most reported associations do not establish differential benefit over another therapy. We distinguish prognosis, candidate treatment interactions, pharmacodynamic monitoring, toxicity associations and mechanistic hypotheses. We also compare validation designs and the reporting of discrimination, calibration and clinical utility across integrated models. The resulting framework is conceptual; it does not provide a combined risk equation or a validated treatment-selection algorithm. Current evidence supports contextual risk assessment and standardized response evaluation. Molecular, cellular and imaging biomarkers require assay- and setting-specific interpretation. Independent validation and prospective studies of prespecified biomarker-guided interventions are needed before risk estimates can justify treatment changes. Not applicable.