Precision medicine in diffuse large B-cell lymphoma: Integrating molecular biomarkers, targeted therapies, and prognostic tools

Abstract

Diffuse large B-cell lymphoma (DLBCL) has undergone a profound transformation in its therapeutic landscape over the past decade, driven by advances in molecular characterization and the emergence of targeted immunotherapies. Although standard immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone achieves high initial remission rates, approximately 30%-40% of patients experience refractory or relapsed disease, underscoring the urgent need for refined risk stratification and innovative treatment approaches. This review synthesizes the current state of precision medicine in DLBCL, emphasizing the integration of molecular biomarkers—including genetic subtypes, tumor microenvironment features, and circulating biomarkers such as circulating tumor DNA—into clinical decision-making. We critically evaluate emerging targeted therapies, including Bruton tyrosine kinase inhibitors, BCL-2 inhibitors, antibody-drug conjugates, and bispecific T-cell engagers (BiTEs), alongside the expanding role of chimeric antigen receptor T-cell therapy. Central to this discussion is the development of robust prognostic models designed to identify high-risk patients most likely to benefit from novel agents, highlighting recent advances in nomogram-based systems derived from Chinese cohorts. Ultimately, we propose that the future of DLBCL management lies not merely in the availability of novel agents, but in the rational sequencing and combination of these modalities based on dynamic molecular monitoring and individualized risk assessment—translating molecular insights into actionable clinical pathways.