New agents and regimens for diffuse large B cell lymphoma
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REVIEW
New agents and regimens for diffuse large B cell lymphoma Liang Wang1,2*, Lin‑rong Li3 and Ken H. Young4*
Abstract As a widely recognized standard regimen, R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is able to cure two-thirds patients with diffuse large B cell lymphoma (DLBCL), and the remaining patients suffer from refractory or relapsed disease due to resistance to R-CHOP and fare poorly. Unsatisfied outcomes for those relapsed/refractory patients prompted efforts to discover new treatment approaches for DLBCL, including chimeric antigen receptor T cells, bispecific T cell engagers, immunomodulatory drugs, immune checkpoint inhibitors, mono‑ clonal antibodies, antibody–drug conjugates, molecular pathway inhibitors, and epigenetic-modifying drugs. Herein, up-to-date data about the most promising treatment approaches for DLBCL are recapitulated, and novel genetic clas‑ sification systems are introduced to guide individualized treatment for DLBCL. Keywords: Diffuse large B cell lymphoma, Chimeric antigen receptor T cells, Immunotherapy, Chemoresistance, Novel agents, Genetic classification Introduction Diffuse large B cell lymphoma (DLBCL) is the most common subtype of lymphoma in adults worldwide, composing about one-third of non-Hodgkin lymphomas (NHLs) diagnosed each year [1], and it represents a considerable socioeconomic burden affecting millions of people [2]. CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen has been used for more than 40 years, and rituximab was approved by the US Food and Drug Administration (FDA) in 2006 for use as firstline treatment of patients with DLBCL in combination with CHOP. Thereafter, R-CHOP regimen has become the standard of care for patients with newly diagnosed DLBCL, even though patients with non-germinal center B cell (non-GCB) subtype of DLBCL have significantly inferior outcomes than their GCB subtype counterparts *Correspondence: [email protected]; [email protected] 1 Department of Hematology, Beijing TongRen Hospital, Capital Medical University, Beijing 100730, China 4 Division of Hematopathology, Department of Pathology, Duke University Medical Center and Cancer Institute, Durham, NC 27710, USA Full list of author information is available at the end of the article
treated with R-CHOP [3]. In recent years, several randomized clinical trials have been conducted by adding novel targeted agents to R-CHOP (the so-called R-CHOP + X mode) in order to improve outcomes for patients with non-GCB or activated B-cell-like (ABC) subtype of DLBCL, such as bortezomib [4], lenalidomide [5], or ibrutinib [6]. However, none of these targeted agents have been found to confer benefits in these trials. Moreover, dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) plus rituximab (DA-EPOCH-R) also failed to show improvement in survival outcomes for patients with DLBCL in a phase III randomized study (CALGB 50303) [7]. Standard R-CHOP regimen is able to cure tw
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