{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:46:30Z","timestamp":1782798390034,"version":"3.54.5"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Patients with high-grade B-cell lymphoma (HGBCL), who are in early relapse or primary refractory, always have poor outcomes. Even intensive chemotherapy or CAR-T cell therapy is not always the best solution. Here is a case of refractory high-grade B-cell lymphoma with MYC, BCL2, and BCL6 rearrangements (triple-hit HGBCL), who achieved complete metabolic remission (CMR) following six cycles of glofitamab monotherapy induction and followed by autologous stem cell transplantation (ASCT) consolidation. The patient has achieved a sustained CMR and a progression-free survival (PFS) of 25 months (ongoing) from progression. Hepatitis B virus (HBV) seroconversion occurred during ASCT before stem cell engraftment, and was effectively suppressed with entecavir. Immune function was monitored in our case by flow cytometry. Downregulation of PD-1 expression on T cells and a reduced proportion of regulatory T cells (Tregs) were observed, consistent with fully activated immune function, which may explain why the patient responded rapidly and maintained durable efficacy. Immune analysis also exhibited B cell subset exhaustion and a disrupted na\u00efve\/memory T cell ratio which suggested an immunosenescence phenotype. It is speculated that an over activation of immune function promotes immunosenescence following bispecific antibody therapy, this needs attention. This case highlights the potential of glofitamab induction followed by ASCT consolidation to achieve durable remission in aggressive triple-hit HGBCL. The immune function after bispecific antibody treatment should be monitored and needs further investigation.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1857464","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:37:15Z","timestamp":1782797835000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Long-term survival of refractory high-grade B-cell lymphoma with MYC, BCL2, and BCL6 rearrangements through glofitamab monotherapy consolidated by ASCT"],"prefix":"10.3389","volume":"17","author":[{"given":"Fang","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Hematology, Xuanwu Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"National Clinical Research Center for Geriatric Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Hematology, Xuanwu Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"National Clinical Research Center for Geriatric Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Hematology, Xuanwu Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"National Clinical Research Center for Geriatric Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuhan","family":"Hui","sequence":"additional","affiliation":[{"name":"Department of Hematology, Xuanwu Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"National Clinical Research Center for Geriatric Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Hematology, Xuanwu Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"National Clinical Research Center for Geriatric Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Hematology, Xuanwu Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"National Clinical Research Center for Geriatric Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanling","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Hematology, Xuanwu Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"National Clinical Research Center for Geriatric Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26068","article-title":"First-line treatment of double-hit and triple-hit lymphomas: Survival and tolerance data from a retrospective multicenter French study","volume":"96","author":"Laude","year":"2021","journal-title":"Am J Hematol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023020780","article-title":"The high-grade B-cell lymphomas: double hit and more","volume":"144","author":"Davies","year":"2024","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1188478","article-title":"Induction treatment in high-grade B-cell lymphoma with a concurrent MYC and BCL2 and\/or BCL6 rearrangement: a systematic review and meta-analysis","volume":"13","author":"Zeremski","year":"2023","journal-title":"Front Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(11)70069-9","article-title":"Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial","volume":"12","author":"Peyrade","year":"2011","journal-title":"Lancet Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-03-769620","article-title":"Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study","volume":"130","author":"Crump","year":"2017","journal-title":"Blood"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2116133","article-title":"Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma","volume":"386","author":"Locke","year":"2022","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2301665","article-title":"Survival with axicabtagene ciloleucel in large B-cell lymphoma","volume":"389","author":"Westin","year":"2023","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(22)00662-6","article-title":"Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial","volume":"399","author":"Kamdar","year":"2022","journal-title":"Lancet"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1082 e1","DOI":"10.1016\/j.jtct.2024.09.007","article-title":"Real-world analysis of barriers to timely administration of chimeric antigen receptor T cell (CAR T) therapy in diffuse large B-cell lymphoma","volume":"30","author":"Hu","year":"2024","journal-title":"Transplant Cell Ther"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.70020","article-title":"Chimeric antigen receptor T-cell therapy for high-grade B-cell lymphoma NOS","volume":"207","author":"Hossain","year":"2025","journal-title":"Br J Haematol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2024014732","article-title":"Outcome of high-grade B-cell lymphoma compared with other large B-cell lymphoma after CAR-T rescue: a DESCAR-T LYSA study","volume":"9","author":"Phina-Ziebin","year":"2025","journal-title":"Blood Adv"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2017.11.023","article-title":"Outcomes after allogeneic stem cell transplantation in patients with double-hit and double-expressor lymphoma","volume":"24","author":"Herrera","year":"2018","journal-title":"Biol Blood Marrow Transplant"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2206913","article-title":"Glofitamab for relapsed or refractory diffuse large B-cell lymphoma","volume":"387","author":"Dickinson","year":"2022","journal-title":"N Engl J Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2024014903","article-title":"Safety and efficacy of glofitamab for relapsed\/refractory large B-cell lymphoma in a multinational real-world study","volume":"9","author":"Shumilov","year":"2025","journal-title":"Blood Adv"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1097\/hs9.0000000000000295","article-title":"The role of autologous stem cell transplantation in the treatment of diffuse large B-cell lymphoma in the era of CAR-T cell therapy","volume":"3","author":"Lekakis","year":"2019","journal-title":"Hemasphere"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-026-56251-9","article-title":"True reactivation versus transient viremia: a retrospective analysis of HBV reactivation in resolved infection","author":"Inuzuka","year":"2026","journal-title":"Sci Rep"},{"key":"B17","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1182\/blood-2021-151266","article-title":"Randomized phase II\/III study of DA-EPOCH-R +\/- venetoclax in previously untreated double hit lymphoma: initial results from alliance A051701","volume":"138","author":"Abramson","year":"2021"},{"key":"B18","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41408-024-00997-w","article-title":"Bispecific antibodies and CAR-T cells: dueling immunotherapies for large B-cell lymphomas","volume":"14","author":"Trabolsi","year":"2024","journal-title":"Blood Cancer J"},{"key":"B19","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1007\/s12032-025-02957-1","article-title":"CAR T-cell immunotherapy as the next horizon in cancer eradication: current landscape, challenges, and future directions","volume":"42","author":"Bharadia","year":"2025","journal-title":"Med Oncol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.45956","article-title":"Cost-effectiveness of axicabtagene ciloleucel and tisagenlecleucel as second-line or later therapy in relapsed or refractory diffuse large B-cell lymphoma","volume":"5","author":"Choe","year":"2022","journal-title":"JAMA Netw Open"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1200\/jco.20.03175","article-title":"Glofitamab, a novel, bivalent CD20-targeting T-cell-engaging bispecific antibody, induces durable complete remissions in relapsed or refractory B-cell lymphoma: A phase I trial","volume":"39","author":"Hutchings","year":"2021","journal-title":"J Clin Oncol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2024.285343","article-title":"New bispecific antibodies in diffuse large B-cell lymphoma","volume":"110","author":"Minson","year":"2025","journal-title":"Haematologica"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30895","article-title":"C-MYC-positive relapsed and refractory, diffuse large B-cell lymphoma: Impact of additional \"hits\" and outcomes with subsequent therapy","volume":"123","author":"Epperla","year":"2017","journal-title":"Cancer"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1056\/nejmc2501018","article-title":"Glofitamab with polatuzumab vedotin in refractory burkitt's lymphoma","volume":"392","author":"Prica","year":"2025","journal-title":"N Engl J Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2024012916","article-title":"Infections in patients with lymphoma treated with bispecific antibodies: a systematic review and meta-analysis","volume":"8","author":"Reynolds","year":"2024","journal-title":"Blood Adv"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1200\/jco-25-00992","article-title":"Efficacy and safety of glofitamab plus polatuzumab vedotin in relapsed\/refractory large B-cell lymphoma including high-grade B-cell lymphoma: results from a phase ib\/II trial","volume":"43","author":"Hutchings","year":"2025","journal-title":"J Clin Oncol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2021.100810","article-title":"Bispecific antibody therapy, its use and risks for infection: Bridging the knowledge gap","volume":"49","author":"Longhitano","year":"2021","journal-title":"Blood Rev"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.41","article-title":"Frequency of regulatory T cells determines the outcome of the T-cell-engaging antibody blinatumomab in patients with B-precursor ALL","volume":"31","author":"Duell","year":"2017","journal-title":"Leukemia"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20130579","article-title":"Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma","volume":"210","author":"Simpson","year":"2013","journal-title":"J Exp Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2023.283758","article-title":"Regulatory T cells hamper the efficacy of T-cell-engaging bispecific antibody therapy","volume":"109","author":"Casey","year":"2024","journal-title":"Haematologica"},{"key":"B31","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1038\/s41392-023-01451-2","article-title":"Immunosenescence: molecular mechanisms and diseases","volume":"8","author":"Liu","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-00927-z","article-title":"Hallmarks of T cell aging","volume":"22","author":"Mittelbrunn","year":"2021","journal-title":"Nat Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1857464\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:37:18Z","timestamp":1782797838000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1857464\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":32,"alternative-id":["10.3389\/fimmu.2026.1857464"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1857464","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]},"article-number":"1857464"}}