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For many years, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) has been the standard first-line treatment for DLBCL; however, pola-R-CHP (polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone) has recently emerged as a new treatment option. In parallel, novel molecularly targeted therapies that target signaling pathways, cellular antigens, and epigenetic regulators associated with high-risk DLBCL are in development. Treatment strategies tailored to the cell of origin or to specific molecular subtypes are also being explored using subtype-specific targeted agents. In addition, agents that have demonstrated efficacy in patients with relapsed or refractory DLBCL\u2014such as the anti-CD19 antibody tafasitamab and immunomodulatory drugs such as golcadomide\u2014are currently under investigation for use in newly diagnosed patients. Immunotherapies, including anti-CD19-chimeric antigen receptor-T therapy and CD20\u00d7CD3 bispecific antibodies (BsAbs), have significantly improved outcomes in patients with relapsed or refractory disease and are now under evaluation as early-line therapies. BsAbs can enable more flexible treatment strategies, including combination regimens with cytotoxic or chemotherapy-free approaches. This review summarizes recent advances and ongoing trials that are investigating novel therapeutic strategies for newly diagnosed DLBCL that may soon be incorporated into clinical practice.<\/jats:p>","DOI":"10.1007\/s10147-026-03062-7","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T15:11:59Z","timestamp":1781277119000},"page":"1137-1150","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Emerging treatment strategies for newly diagnosed diffuse large B-cell lymphoma"],"prefix":"10.1007","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6547-3181","authenticated-orcid":false,"given":"Kana","family":"Miyazaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"3062_CR1","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1056\/NEJMra2027612","volume":"384","author":"LH Sehn","year":"2021","unstructured":"Sehn LH, Salles G (2021) Diffuse large B-cell lymphoma. 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