Laurie H. Sehn, MD, MPH

The ongoing GO29365 study of combination regimens containing polatuzumab vedotin (Polivy) for patients with relapsed or refractory diffuse large B-cell lymphoma added an additional 106 patients to confirm preliminary findings of safety and efficacy.

Rationally designed clinical trials investigating novel agents in patient populations enriched for those who are most likely to benefit will be instrumental for expediting progress. With respect to DLBCL, it has become clear that one treatment no longer fits all.

The most common subtype of aggressive non-Hodgkin’s lymphomais diffuse large B-cell lymphoma (DLBCL). Diffuse large B-cell lymphomarepresents a heterogeneous entity, with 5-year overall survivalrates ranging from 26% to 73%. Microarray gene expression studieshave confirmed that biologically distinct subgroups exist within DLBCL,and can be correlated with outcome. Initial management is usuallyguided by stage of disease at presentation. Approximately 25% of patientswith DLBCL present with limited-stage disease and are treatedwith combined-modality therapy (brief chemotherapy and involved-fieldradiation). Most patients present with advanced-stage disease and requiretreatment with an extended course of chemotherapy. The CHOP(cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone)chemotherapy regimen has been the mainstay of therapy sinceits development in the 1970s, as more intensive chemotherapy regimensfailed to show additional benefit. The era of monoclonal antibodieshas transformed treatment practices for aggressive lymphoma andhas led to a significant improvement in outcome. A randomized trialcomparing the use of rituximab (Rituxan), a chimeric anti-CD20 IgG1monoclonal antibody, combined with CHOP chemotherapy vs CHOPchemotherapy alone for elderly patients with advanced-stage DLBCLdemonstrated a significant benefit for the combination approach. Thisfinding has now been confirmed in two additional randomized, controlledtrials and a population-based analysis, making CHOP andrituximab the standard of care for all newly diagnosed patients withDLBCL. Despite this advance, newer therapies are needed and manyare under active investigation. The insights gained from molecular techniquessuch as gene expression profiling should permit identificationof additional lymphoma-specific therapeutic targets and the developmentof novel agents that take into account underlying biology andallow for greater tailoring of therapy.