{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:56:29Z","timestamp":1790690189714,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2019,7,9]],"date-time":"2019-07-09T00:00:00Z","timestamp":1562630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2019,9,15]]},"abstract":"<jats:p>Diffuse large B\u2010cell lymphoma (DLBCL) is a clinically and biologically heterogeneous disease. Diagnostic tools in the clinic can now identify distinct subsets characterized by unique molecular features, which are increasingly transforming how these patients are managed. Activated B\u2013cell\u2010like DLBCL is characterized by NF\u2010\u03baB activation and chronic B\u2010cell receptor signaling and may be targeted with lenalidomide or ibrutinib in the relapsed setting. Germinal center\u2010like DLBCL is enriched for activating <jats:italic>EZH2<\/jats:italic> mutations, and encouraging activity has been observed for the <jats:italic>EZH2<\/jats:italic> inhibitor tazemetostat, which now has a fast\u2010track US Food and Drug Administration designation. Double\u2010hit lymphoma is a high\u2010grade B\u2010cell lymphoma characterized by translocations of MYC and BCL2 and\/or BCL6 and carries a poor prognosis. Intensive chemoimmunotherapy strategies appear to be superior to standard R\u2010CHOP (rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone) as initial therapy, and anti\u2010CD19 chimeric antigen receptor T cells are inducing remission in patients with relapsed\/refractory disease who previously had few available options. Primary mediastinal (thymic) large B\u2010cell lymphoma is a molecularly distinct large\u2010cell lymphoma with clinical and molecular features that overlap with those of classical Hodgkin lymphoma. R\u2010CHOP has been associated with an unacceptably high rate of primary treatment failure in this young population, whereas dose\u2010adjusted EPOCH\u2010R (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab) produces durable remissions without the need for radiotherapy in most patients. For relapsed\/refractory disease, immune checkpoint inhibitors targeting PD\u20101 have shown promising activity in chemotherapy\u2010refractory disease, as have anti\u2010CD19 chimeric antigen receptor T cells. Additional therapeutic targets, including JAK2, continue to be evaluated. The identification of discrete biological subsets is steadily moving us away from a \u201cone\u2010size\u2010fits\u2010all\u201d approach in DLBCL.<\/jats:p>","DOI":"10.1002\/cncr.32145","type":"journal-article","created":{"date-parts":[[2019,7,9]],"date-time":"2019-07-09T08:25:40Z","timestamp":1562660740000},"page":"3111-3120","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Hitting back at lymphoma: How do modern diagnostics identify high\u2010risk diffuse large B\u2010cell lymphoma subsets and alter treatment?"],"prefix":"10.1002","volume":"125","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8467-9257","authenticated-orcid":false,"given":"Jeremy S.","family":"Abramson","sequence":"first","affiliation":[{"name":"Center for Lymphoma, Massachusetts General Hospital Cancer Center and Department of Medicine Harvard Medical School Boston 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