{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:28:01Z","timestamp":1792898881299,"version":"4.5.0"},"reference-count":119,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Relapsed or refractory (R\/R) B-cell non-Hodgkin lymphomas (B-NHL) remain associated with poor outcomes despite advances in chemoimmunotherapy and chimeric antigen receptor (CAR) T-cell therapy. Many patients are ineligible for or relapse after cellular therapies, highlighting the need for effective off-the-shelf immunotherapeutic approaches. CD20 \u00d7 CD3 bispecific antibodies (BsAbs) redirect endogenous T cells against malignant B cells and have emerged as a promising therapeutic class in B-NHL. To summarize current clinical evidence regarding mosunetuzumab, glofitamab, epcoritamab, and odronextamab in B-NHL, focusing on efficacy, safety, and emerging therapeutic applications. Materials and Methods: A structured review of published phase I\u2013III clinical trials evaluating the four currently approved CD20 \u00d7 CD3 BsAbs in B-NHL was conducted. Efficacy outcomes, durability of response, and safety data were assessed across indolent and aggressive lymphoma subtypes. Results: CD20 \u00d7 CD3 BsAbs demonstrated substantial and durable clinical activity in heavily pretreated B-NHL, including patients with prior CAR T-cell exposure. Mosunetuzumab showed high response rates and durable remissions in follicular lymphoma (FL), while glofitamab demonstrated significant efficacy in aggressive lymphomas, particularly diffuse large B-cell lymphoma (DLBCL). Epcoritamab exhibited consistent activity across lymphoma subtypes with favorable tolerability supported by subcutaneous administration and step-up dosing. Odronextamab also demonstrated clinically meaningful responses in both FL and DLBCL, including high-risk populations. Across studies, cytokine release syndrome (CRS) was the most common adverse event, predominantly low grade and manageable with established mitigation strategies. Immune effector cell-associated neurotoxicity syndrome (ICANS) was uncommon. Infections and hematologic toxicities, particularly neutropenia, represented clinically relevant adverse events across all treatment programs, highlighting the need for special supportive care. Conclusions: CD20 \u00d7 CD3 BsAbs represent a major therapeutic advancement in R\/R B-NHL, combining high clinical activity, manageable toxicity, and off-the-shelf availability. Their expanding integration into earlier treatment settings and combination strategies is expected to further reshape the therapeutic landscape of B-NHL.<\/jats:p>","DOI":"10.3390\/medicina62061056","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T10:06:56Z","timestamp":1780049216000},"page":"1056","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["CD20 \u00d7 CD3 Bispecific Antibodies in B-Cell Non-Hodgkin Lymphomas: Current Evidence, Therapeutic Integration, and Future Directions"],"prefix":"10.3390","volume":"62","author":[{"given":"Polyxeni","family":"Giamaiou","sequence":"first","affiliation":[{"name":"Department of Haematology and Bone Marrow Transplantation Unit, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1219-8715","authenticated-orcid":false,"given":"Rodanthi","family":"Fioretzaki","sequence":"additional","affiliation":[{"name":"Department of Haematology and Bone Marrow Transplantation Unit, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8766-1853","authenticated-orcid":false,"given":"Theodoros P.","family":"Vassilakopoulos","sequence":"additional","affiliation":[{"name":"Department of Haematology and Bone Marrow Transplantation Unit, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8197-9895","authenticated-orcid":false,"given":"Maria","family":"Dimou","sequence":"additional","affiliation":[{"name":"Department of Haematology and Bone Marrow Transplantation Unit, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1007\/s12325-017-0612-x","article-title":"Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience","volume":"34","author":"Salles","year":"2017","journal-title":"Adv. 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