Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma in the world. Clinically, biologically, and pathologically, DLBCL is a heterogeneous entity with a range of potential outcomes. Immunochemotherapy regimens, consisting of the chimeric monoclonal anti-CD20 antibody rituximab in combination with chemotherapy, have improved the outcomes. Relapsed DLBCL is generally treated with salvage immunochemotherapy followed by high-dose therapy and autologous stem cell transplantation; however, DLBCL is not yet curable in up to a third of patients. The real promise for cure lies in novel agents and their rational combinations. The improved understanding of DLBCL subtypes and gene expression profiling has led to the identification of targeted drugs that may allow for subtype specific therapy. We have summarized the existing data on the prognostic factors and the treatment of DLBCL, including the use of novel agents such as lenalidomide, carfilzomib, and ibrutinib. We also share our thoughts on the direction of future clinical trials.
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