{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:55Z","timestamp":1787027815758,"version":"build-2736575974"},"reference-count":116,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Associazione Italiana per la Ricerca sul Cancro (AIRC) Foundation Milan, Italy","award":["21198"],"award-info":[{"award-number":["21198"]}]},{"name":"Associazione Italiana per la Ricerca sul Cancro (AIRC) Foundation Milan, Italy","award":["PNRR-MCNT2-2023-12378037"],"award-info":[{"award-number":["PNRR-MCNT2-2023-12378037"]}]},{"name":"AGING Project\u2014Department of Excellence\u2014DIMET, Universit\u00e0 del Piemonte Orientale, Novara, Italy","award":["21198"],"award-info":[{"award-number":["21198"]}]},{"name":"AGING Project\u2014Department of Excellence\u2014DIMET, Universit\u00e0 del Piemonte Orientale, Novara, Italy","award":["PNRR-MCNT2-2023-12378037"],"award-info":[{"award-number":["PNRR-MCNT2-2023-12378037"]}]},{"name":"Italian MoH, Rome, Italy","award":["21198"],"award-info":[{"award-number":["21198"]}]},{"name":"Italian MoH, Rome, Italy","award":["PNRR-MCNT2-2023-12378037"],"award-info":[{"award-number":["PNRR-MCNT2-2023-12378037"]}]},{"name":"AIL Novara VCO, Novara, Italy","award":["21198"],"award-info":[{"award-number":["21198"]}]},{"name":"AIL Novara VCO, Novara, Italy","award":["PNRR-MCNT2-2023-12378037"],"award-info":[{"award-number":["PNRR-MCNT2-2023-12378037"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL) worldwide. Currently, approximately sixty percent of patients are cured with R-CHOP as frontline treatment, while the remaining patients experience primary refractory or relapsed (R\/R) disease. Recently, the introduction of Pola-R-CHP as front-line therapy has represented a major advance in the management of DLBCL, resulting in improved outcomes. Prognosis of R\/R DLBCL patients is poor, particularly for those eligible neither for chimeric antigen receptor (CAR) T-cell therapy nor autologous stem cell transplantation (ASCT), representing a significant unmet clinical need. The advent of bispecific monoclonal antibodies (BsAbs), such as bispecific T-cell engagers (BiTEs), dual affinity retargeting (DART) molecules and IgG-like bispecific antibodies, offers a novel promising therapeutic approach in the treatment of DLBCL, both as frontline treatment and in the R\/R setting. BsAbs simultaneously engage two different antigens, a tumor-associated antigen and an immune cell antigen, redirecting T-cells against malignant cells and enhancing the immune response. Most BsAbs developed for the treatment of NHLs engage T-cells via CD3 and malignant B-cells via CD20, a surface antigen expressed on most lymphomatous cells. Engagement of malignant B-cells by BsAbs activates T-cells, leading to the release of multiple cytokines and potentially to two characteristic adverse events: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The most extensively studied BsAbs, in both the frontline and relapsed\/refractory (R\/R) settings, include epcoritamab, glofitamab, mosunetuzumab, and odronextamab. Epcoritamab and glofitamab have received FDA and EMA approval for R\/R DLBCL after two or more systemic line of therapies. EMA has also approved glofitamab in combination with gemcitabine and oxaliplatin (GemOx) for patients with R\/R DLBCL ineligible for ASCT, whereas this indication has not been approved by FDA. Odronextamab is approved by EMA for R\/R DLBCL and FL in patients who have received at least two prior lines of therapy, but it has not been approved by FDA. Mosunetuzumab is approved by both agencies\u2014but only for R\/R follicular lymphoma (FL). BsAbs represent a breakthrough therapy in the treatment of DLBCL, especially in R\/R diseases. The purpose of this article is to review the landscape of BsAbs in DLBCL.<\/jats:p>","DOI":"10.3390\/cancers17193258","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T12:04:52Z","timestamp":1759925092000},"page":"3258","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Bispecific Monoclonal Antibodies in Diffuse Large B-Cell Lymphoma: Dawn of a New Era in Targeted Therapy"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5710-2781","authenticated-orcid":false,"given":"Mattia","family":"Schipani","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont and Azienda Ospedaliero\u2014Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9709-4935","authenticated-orcid":false,"given":"Matteo","family":"Bellia","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont and Azienda Ospedaliero\u2014Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Sella","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont and Azienda Ospedaliero\u2014Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Dondolin","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont and Azienda Ospedaliero\u2014Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Greco","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont and Azienda Ospedaliero\u2014Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3969-0112","authenticated-orcid":false,"given":"Abdurraouf Mokhtar","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont and Azienda Ospedaliero\u2014Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Deambrogi","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont and Azienda Ospedaliero\u2014Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Moia","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont and Azienda Ospedaliero\u2014Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4681-0151","authenticated-orcid":false,"given":"Gianluca","family":"Gaidano","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont and Azienda Ospedaliero\u2014Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Bruna","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont and Azienda Ospedaliero\u2014Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.3324\/haematol.2016.148809","article-title":"Non-Hodgkin Lymphoma in the Developing World: Review of 4539 Cases from the International Non-Hodgkin Lymphoma Classification Project","volume":"101","author":"Perry","year":"2016","journal-title":"Haematologica"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1038\/bjc.2015.94","article-title":"Lymphoma Incidence, Survival and Prevalence 2004\u20132014: Sub-Type Analyses from the UK\u2019s Haematological Malignancy Research Network","volume":"112","author":"Smith","year":"2015","journal-title":"Br. 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