Review ArticlesMolecular Classification and Treatment of Diffuse Large B-Cell Lymphoma and Primary Mediastinal B-Cell LymphomaRoschewski, Mark MD; Phelan, James D. PhD; Wilson, Wyndham H. MD, PhD Author Information From the Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. All authors researched the data for the article, made a substantial contribution to discussion of the content, wrote the article, and reviewed and edited the manuscript prior to submission. Reprints: Mark Roschewski, MD, Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bldg 10, Room 4N115, National Institutes of Health, Bethesda, MD 20892. E-mail: [email protected]. The Cancer Journal: 5/6 2020 - Volume 26 - Issue 3 - p 195-205 doi: 10.1097/PPO.0000000000000450 Buy Metrics Abstract Diffuse large B-cell lymphoma (DLBCL) encompasses a group of aggressive B-cell non-Hodgkin lymphomas with striking genetic heterogeneity and variable clinical presentations. Among these is primary mediastinal B-cell lymphoma (PMBL), which has unique clinical and molecular features resembling Hodgkin lymphoma. Treatment of DLBCL is usually curative, but identifiable subsets at highest risk for treatment failure may benefit from intensified chemotherapy regimens and/or targeted agents added to frontline therapy. Recent comprehensive genomic analyses have identified distinct genetic subtypes of DLBCL with characteristic genetic drivers and signaling pathways that are targetable. Immune therapy with chimeric antigen receptor T cells and checkpoint inhibitors has revolutionized the treatment of relapsed or refractory disease, and antibody drug conjugates have weaponized otherwise intolerable cytotoxic agents. Ongoing clinical trials are further refining the specificity of these approaches in different genetic subtypes and moving them from the setting of recurrent disease to frontline treatment in high-risk patient populations. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.