Rituximab-Based Therapy in Newly Diagnosed Diffuse Large B-Cell Lymphoma Patients: Individualized Risk-Adapted Therapy Approach Using Molecular Subtypes.

Rituximab (R) with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) is the current standard of care as first-line treatment for diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype. Patients who fail R-CHOP have a poor outcome with relapse or refractory disease resulting in fatality in majority of patients. This review focuses on novel therapies which are currently being assessed as first-line treatment in combination with R-CHOP in patients with DLBCL. Targeted drug development is a possibility with recent developments like gene expression profiling, RNA interference screening, DNA sequencing, identification of new biomarkers and signaling pathways. Newer drugs such as bortezomib, lenalidomide, and ibrutinib are being investigated as first-line therapy in combination with R-CHOP (XR-CHOP) in the activated B-cell (ABC) subtype of DLBCL. Additionally, inhibitors of BCL6, EZH2, and PI3K/Akt/mTOR are being considered for treatment of germinal center B-cell (GCB) subtype of DLBCL in patients with probable survival of less than 5 years. Double- or triple-hit lymphomas and double-expressor lymphomas also have poor prognosis and research to identify effective first-line therapy in these patients remains an unmet need. Presently, individualized approach that includes effective therapeutic combinations with acceptable safety profiles for use in routine practice, especially in patients likely to have poor outcomes such as relapsed/refractory DLBCL remains a distant possibility. Current evidence shows that untreated high risk patients do not have the greater benefit with use of newer drugs compared with R-CHOP. Therefore, R-CHOP remains the first-line treatment for newly diagnosed DLBCL patients.