{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:41:05Z","timestamp":1792813265952,"version":"4.5.0"},"reference-count":23,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:00:00Z","timestamp":1792713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:00:00Z","timestamp":1792713600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Younger patients with high\u2010risk diffuse large B\u2010cell lymphoma (DLBCL) frequently have unfavourable outcomes. We conducted a prospective phase II study evaluating ibrutinib plus rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R\u2010CHOEP+I) in patients aged 18\u201360\u2009years with DLBCL and age\u2010adjusted international prognostic index \u22652. Patients received ibrutinib (560\u2009mg daily, d1\u2010112) combined with eight\u2009cycles of R\u2010CHOEP q2w. The primary end\u2010point was 2\u2010year progression\u2010free survival (PFS). Outcomes were compared exploratorily with those of patients with identical inclusion criteria treated with R\u2010CHOEP alone in the R\u2010MegaCHOEP phase III trial (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009130). Forty patients started R\u2010CHOEP+I. Ibrutinib was administered for a median of 96\u2009days, and 42% of patients completed treatment fully according to protocol. The overall response rate was 92%. Sixty\u2010eight per cent received all R\u2010CHOEP cycles compared with 88% in R\u2010MegaCHOEP; 22% vs. 49% of patients with bulky and\/or extranodal disease underwent radiotherapy. With a median follow\u2010up of 31\u2009months, 2\u2010year PFS was 83% (95% CI, 71\u201395) vs. 75% (95% CI, 67\u201382) after R\u2010CHOEP alone (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.237). Exploratory cell\u2010of\u2010origin analyses suggested favourable outcomes in activated B\u2010cell\u2010type disease, but these findings remain descriptive. Grade \u22653 haematological adverse events were frequent, although no treatment\u2010related deaths occurred. In this prematurely closed phase II study, the addition of ibrutinib to R\u2010CHOEP showed encouraging activity. However, findings remain exploratory and hypothesis generating only.\n                  <\/jats:p>","DOI":"10.1111\/bjh.70902","type":"journal-article","created":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:11:22Z","timestamp":1792811482000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ibrutinib and standard immunochemotherapy in younger, high\u2010risk patients with diffuse large B\u2010cell lymphoma: A phase II study of GLA"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0178-1729","authenticated-orcid":false,"given":"Evgenii","family":"Shumilov","sequence":"first","affiliation":[{"name":"Department of Medicine A, Hematology, Oncology and Pneumology University Hospital Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0834-8111","authenticated-orcid":false,"given":"Marita","family":"Ziepert","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Statistics, and Epidemiology University of Leipzig  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birte","family":"Friedrichs","sequence":"additional","affiliation":[{"name":"Department of Hematolgy, Oncology and Immunolgy University Hospital of Duesseldorf  Duesseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5655-3155","authenticated-orcid":false,"given":"Susanne","family":"Ghandili","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7682-8563","authenticated-orcid":false,"given":"Kai","family":"Wille","sequence":"additional","affiliation":[{"name":"University Clinic for Hematology, Oncology, Hemostaseology and Palliative Care Johannes Wesling Medical Center Minden, University of Bochum  Minden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram","family":"Glass","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, and Tumor Immunology Helios Klinikum Berlin\u2010Buch  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike","family":"Nickelsen","sequence":"additional","affiliation":[{"name":"Oncology Lerchenfeld  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3782-2158","authenticated-orcid":false,"given":"Peter","family":"Borchmann","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Medical Faculty and University Hospital of Cologne University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Viardot","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III University Hospital of Ulm  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6904-2821","authenticated-orcid":false,"given":"Andrea","family":"Kerkhoff","sequence":"additional","affiliation":[{"name":"Department of Medicine A, Hematology, Oncology and Pneumology University Hospital Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Berning","sequence":"additional","affiliation":[{"name":"Department of Medicine A, Hematology, Oncology and Pneumology University Hospital Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3603-761X","authenticated-orcid":false,"given":"Sebastian","family":"B\u00f6ttcher","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine, Medical Clinic III \u2010 Hematology, Oncology and Palliative Medicine, Special Hematology Laboratory Rostock University Medical Center  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Wirths","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, Clinical Immunology and Rheumatology, Center for Internal Medicine University Hospital Tuebingen  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Kewitz","sequence":"additional","affiliation":[{"name":"Center for Clinical Trials Muenster University of Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4767-3275","authenticated-orcid":false,"given":"Mathias","family":"H\u00e4nel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III Klinikum Chemnitz  Chemnitz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Dierlamm","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Rosenwald","sequence":"additional","affiliation":[{"name":"Institute of Pathology University of Wuerzburg  Wuerzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Altmann","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Statistics, and Epidemiology University of Leipzig  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Lenz","sequence":"additional","affiliation":[{"name":"Department of Medicine A, Hematology, Oncology and Pneumology University Hospital Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Department of Medicine A, Hematology, Oncology and Pneumology University Hospital Muenster  Muenster 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Haematol"},{"issue":"12","key":"e_1_2_13_9_1","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1038\/s41375-024-02420-6","article-title":"Pola\u2010R\u2010CHP or R\u2010CHOEP for first\u2010line therapy of younger patients with high\u2010risk diffuse large B\u2010cell lymphoma: a retrospective comparison of two randomized phase 3 trials","volume":"38","author":"Lenz G","year":"2024","journal-title":"Leukemia"},{"issue":"8","key":"e_1_2_13_10_1","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1038\/nm.3884","article-title":"Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma","volume":"21","author":"Wilson WH","year":"2015","journal-title":"Nat Med"},{"issue":"15","key":"e_1_2_13_11_1","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1200\/JCO.18.02403","article-title":"Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non\u2010germinal center B\u2010cell diffuse large B\u2010cell lymphoma","volume":"37","author":"Younes A","year":"2019","journal-title":"J Clin Oncol"},{"issue":"27","key":"e_1_2_13_12_1","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1200\/JCO.2013.54.8800","article-title":"Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non\u2010Hodgkin lymphoma: the Lugano classification","volume":"32","author":"Cheson BD","year":"2014","journal-title":"J Clin Oncol"},{"issue":"6","key":"e_1_2_13_13_1","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1093\/annonc\/mdg249","article-title":"Practicability and acute haematological toxicity of 2\u2010 and 3\u2010weekly CHOP and CHOEP chemotherapy for aggressive non\u2010Hodgkin's lymphoma: results from the NHL\u2010B trial of the GermanHigh\u2010grade non\u2010Hodgkin's lymphoma study group (DSHNHL)","volume":"14","author":"Wunderlich A","year":"2003","journal-title":"Ann Oncol"},{"issue":"12","key":"e_1_2_13_14_1","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1200\/JCO.20.01366","article-title":"ROBUST: a phase III study of lenalidomide plus R\u2010CHOP versus placebo plus R\u2010CHOP in previously untreated patients with ABC\u2010type diffuse large B\u2010cell lymphoma","volume":"39","author":"Nowakowski GS","year":"2021","journal-title":"J Clin Oncol"},{"issue":"31","key":"e_1_2_13_15_1","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.1200\/JCO.2017.73.3402","article-title":"Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated diffuse large B\u2010cell lymphoma","volume":"35","author":"Vitolo U","year":"2017","journal-title":"J Clin Oncol"},{"issue":"21","key":"e_1_2_13_16_1","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1200\/JCO.18.01994","article-title":"Dose\u2010adjusted EPOCH\u2010R compared with R\u2010CHOP as frontline therapy for diffuse large B\u2010cell lymphoma: clinical outcomes of the phase III intergroup trial Alliance\/CALGB 50303","volume":"37","author":"Bartlett NL","year":"2019","journal-title":"J Clin Oncol"},{"issue":"23","key":"e_1_2_13_17_1","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1200\/JCO-25-00481","article-title":"Glofitamab combined with Pola\u2010R\u2010CHP or R\u2010CHOP as first therapy in younger patients with high\u2010risk large B\u2010cell lymphoma: results from the COALITION study","volume":"43","author":"Minson A","year":"2025","journal-title":"J Clin Oncol"},{"key":"e_1_2_13_18_1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1182\/blood-2024-198023","article-title":"Fixed\u2010duration Epcoritamab + R\u2010CHOP induces high complete response rates in patients with previously untreated diffuse large B\u2010cell lymphoma with high\u2010risk features: long\u2010term results from the Epcore NHL\u20102 trial","volume":"144","author":"Falchi L","year":"2024","journal-title":"Blood"},{"issue":"9","key":"e_1_2_13_19_1","article-title":"Large B\u2010cell lymphoma (LBCL): EHA clinical practice guidelines for diagnosis, treatment, and follow\u2010up","volume":"9","author":"Thieblemont C","year":"2025","journal-title":"Hema"},{"issue":"4","key":"e_1_2_13_20_1","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1056\/NEJMoa2115304","article-title":"Polatuzumab Vedotin in previously untreated diffuse large B\u2010cell lymphoma","volume":"386","author":"Tilly H","year":"2021","journal-title":"N Engl J Med"},{"issue":"10","key":"e_1_2_13_21_1","doi-asserted-by":"crossref","first-page":"2774","DOI":"10.3324\/haematol.2021.278654","article-title":"Acalabrutinib for treatment of diffuse large B\u2010cell lymphoma: results from a phase Ib study","volume":"106","author":"Strati P","year":"2021","journal-title":"Haematologica"},{"issue":"6","key":"e_1_2_13_22_1","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.ccell.2017.04.012","article-title":"Inhibition of B cell receptor signaling by ibrutinib in primary CNS lymphoma","volume":"31","author":"Lionakis MS","year":"2017","journal-title":"Cancer Cell"},{"issue":"16","key":"e_1_2_13_23_1","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2022.40.16_suppl.TPS7590","article-title":"frontMIND: a phase III, randomized, double\u2010blind study of tafasitamab + lenalidomide + R\u2010CHOP versus R\u2010CHOP alone for newly diagnosed high\u2010intermediate and high\u2010risk diffuse large B\u2010cell lymphoma","volume":"40","author":"Vitolo U","year":"2022","journal-title":"J Clin Oncol"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(26)00866\u20104"}],"container-title":["British Journal of 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History"}},{"value":"2026-09-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"bjh.70902"}}