Prognostic molecular biomarkers in diffuse large B-cell lymphoma in the rituximab era and their therapeutic implications

Abstract

Diffuse large B-cell lymphoma (DLBCL) represents a group of tumors characterized by substantial heterogeneity in terms of their pathological and biological features, a causal factor of their varied clinical outcome. This variation has persisted despite the implementation of rituximab in treatment regimens over the last 20 years. In this context, prognostic biomarkers are of great importance in order to identify high-risk patients that might benefit from treatment intensification or the introduction of novel therapeutic agents. Herein, we review current knowledge on specific immunohistochemical or genetic biomarkers that might be useful in clinical practice. Gene-expression profiling is a tool of special consideration in this effort, as it has enriched our understanding of DLBCL biology and has allowed for the classification of DLBCL by cell-of-origin as well as by more elaborate molecular signatures based on distinct gene-expression profiles. These subgroups might outperform individual biomarkers in terms of prognostication; however, their use in clinical practice is still limited. Moreover, the underappreciated role of the tumor microenvironment in DLBCL prognosis is discussed in terms of prognostic gene-expression signatures, as well as in terms of individual biomarkers of prognostic significance. Finally, the efficacy of novel therapeutic agents for the treatment of DLBCL patients are discussed and an evidence-based therapeutic approach by specific genetic subgroup is suggested.

Identification and Validation of a Prognostic Prediction Model in Diffuse Large B-Cell Lymphoma

“…It has been established that DELs are generally aggressive and respond poorly to currently available therapies ( 9 , 44 , 45 ). Moreover, IPI and age-adjusted IPI have been developed as models for predicting outcomes based on clinical factors from more than 4,000 patients ( 46 , 47 ). However, despite overall improvements in DLBCL patient outcomes, 30%–40% of patients develop relapsed or refractory disease ( 48 ).…”

“…showed the presence of CD1a+ dendritic cells (DCs) and increased granzyme B+ T cells within tumors was associated with a favorable prognosis ( 51 ). It has been established that M1 cells play a proinflammatory and anticancer role in the TME of DLBCL, while M2 type plays an immunosuppressive role to promote cancer progression ( 47 , 52 , 53 ). Herein, we used two algorithms to evaluate the TME of patients with DLBCL and found that patients in the high-risk score group exhibited significant B-cell infiltration with mild infiltration of M0, M1, CD8+ T cells, and DCs.…”

Comprehensive treatment for primary right renal diffuse large B-cell lymphoma with a renal vein tumor thrombus: A case report

“…Emerging immunotherapy options and targeted therapies may provide chemotherapy-free first-line approaches for DLBCL[ 9 ]. However, recent evidence suggests that COO, concurrent rearrangements of MYC/BCL2/BCL6, the characterization of DH/TH HGBL, and the overexpression of MYC/BCL2 result in highly aggressive clinical behavior, resistance to standard chemotherapy and extremely poor outcomes[ 10 , 11 ]. Side effect management and challenges to effective therapy, including unfavorable biological features, individual vulnerabilities and toxicities of cytotoxic chemotherapy, are the main concerns.…”

Overexpression of BCL2, BCL6, VEGFR1 and TWIST1 in Circulating Tumor Cells Derived from Patients with DLBCL Decreases Event-Free Survival

“…However, approximately 30 to 40% of patients will develop a recurrent or refractory disease that remains one of the main causes of morbidity and mortality in patients who have this pathology. 18 The monitoring of the disease during the progression of DLBCL to a disseminated state is usually identified with image studies such as PET; however, its access is limited and expensive, so the need to have molecular-specific, sensitive and low-cost strategies arises. The search for biomarkers in CTCs of liquid biopsies of peripheral blood might cover this need and will help us to predict, prevent and customize therapeutic strategies that will help improve the quality of life of patients.…”