{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:53:09Z","timestamp":1791222789666,"version":"4.1.0"},"reference-count":0,"publisher":"American Society of Hematology","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Older or medically unfit patients with diffuse large B-cell lymphoma (DLBCL) frequently cannot tolerate standard anthracycline-based immunochemotherapy, creating a persistent unmet clinical need. We conducted a multicenter, international, open-label phase I\/II trial evaluating an immunotherapy-based first-line approach using subcutaneous mosunetuzumab in combination with polatuzumab vedotin in previously untreated patients classified as unfit or frail by simplified geriatric assessment (sGA). Participants received six cycles of polatuzumab vedotin with step-up-dosing of subcutaneous mosunetuzumab, followed by mosunetuzumab monotherapy for a planned total of eight cycles. The primary endpoint was objective response rate (ORR) at end of treatment, assessed by independent review using PET-CT Lugano 2014 criteria. Among participants treated at full dose (n=101), the median age was 81 years with 58% classified as unfit and 41% as frail by sGA. The ORR at the end of treatment was 61.4% (95% CI, 51.1-70.9), with a complete response (CR) rate of 56.4%. The best observed ORR and CR rates on therapy were 80.2% and 66.3%, respectively. With a median follow-up of 36.5 months, median investigator-assessed duration of response and overall survival were not reached; estimated 2-year progression-free and overall survival were 52.2% and 62.4%, respectively. Cytokine release syndrome occurred in 30.6% of participants and was predominantly grade 1. Infection-related mortality was observed, largely during the COVID-19 pandemic and among participants classified as frail. This geriatric assessment-guided treatment demonstrated durable efficacy and may represent a potential first-line treatment option for carefully selected unfit or frail patients with newly diagnosed DLBCL. Trial registration: #NCT03677154.<\/jats:p>","DOI":"10.1182\/blood.2026035116","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:12:24Z","timestamp":1791220344000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":0,"title":["Mosunetuzumab and Polatuzumab Vedotin as First-line Treatment for Large B Cell Lymphoma in Older Unfit or Frail Patients"],"prefix":"10.1182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6472-6658","authenticated-orcid":false,"given":"Adam J.","family":"Olszewski","sequence":"first","affiliation":[{"name":"Brown University, Providence, Rhode Island, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert A.","family":"Eradat","sequence":"additional","affiliation":[{"name":"UCLA, Los Angeles, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham","family":"Avigdor","sequence":"additional","affiliation":[{"name":"Sheba Medical Center, Tel Hashomer, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7076-6501","authenticated-orcid":false,"given":"Netanel A.","family":"Horowitz","sequence":"additional","affiliation":[{"name":"Rambam Health Care Campus, Haifa, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S.","family":"McKinney","sequence":"additional","affiliation":[{"name":"Duke University School of Medicine, Durham, North Carolina, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Tae","family":"Lee","sequence":"additional","affiliation":[{"name":"UNIVERSITY OF MARYLAND, Baltimore, Maryland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8229-1208","authenticated-orcid":false,"given":"Juan Miguel","family":"Bergua Burgues","sequence":"additional","affiliation":[{"name":"Hospital San Pedro de Alc\u00e1ntara. C\u00e1ceres, Caceres, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Rodriguez Izquierdo","sequence":"additional","affiliation":[{"name":"Hospital Universitario 12 de Octubre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Bastos-Oreiro","sequence":"additional","affiliation":[{"name":"Hospital General Universitario Gregorio Mara\u00f1on, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1722-4807","authenticated-orcid":false,"given":"Chezi","family":"Ganzel","sequence":"additional","affiliation":[{"name":"The Hematology department, Shaare Zedek Medical Center, Israel; Faculty of Medicine, Hebrew University of Jerusalem, Israel, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6145-4426","authenticated-orcid":false,"given":"Tae Min","family":"Kim","sequence":"additional","affiliation":[{"name":"Seoul National University Hospital, Seoul, Korea, Republic of"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3362-8200","authenticated-orcid":false,"given":"Youngwoo","family":"Jeon","sequence":"additional","affiliation":[{"name":"Yeouido St. Mary's Hospital, Seoul, Korea, Republic of"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8437-2797","authenticated-orcid":false,"given":"Micha\u0142","family":"Taszner","sequence":"additional","affiliation":[{"name":"Medical University of Gda\u0144sk, Faculty of Medicine, Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2606-0533","authenticated-orcid":false,"given":"Mayur S.","family":"Narkhede","sequence":"additional","affiliation":[{"name":"Mercy Health Care Institute, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Seog","family":"Kim","sequence":"additional","affiliation":[{"name":"Samsung Medical Center, SEOUL, Korea, Republic of"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho-Jin","family":"Shin","sequence":"additional","affiliation":[{"name":"Pusan National University Hospital, Busan, Korea, Republic of"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8908-4954","authenticated-orcid":false,"given":"Dariusz","family":"Woszczyk","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences, University of Opole, Opole, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neta","family":"Goldschmidt","sequence":"additional","affiliation":[{"name":"Hadassah-Hebrew University medical center, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avrita","family":"Singh","sequence":"additional","affiliation":[{"name":"Genentech, Inc., South San Francisco, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Wei","sequence":"additional","affiliation":[{"name":"Genentech, Inc., South San Francisco, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jue","family":"Wang","sequence":"additional","affiliation":[{"name":"Genentech, Inc., South San Francisco, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"MD, PhD","given":"Connie Lee","family":"Batlevi","sequence":"additional","affiliation":[{"name":"Genentech, Inc., South San Francisco, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wahib","family":"Ead","sequence":"additional","affiliation":[{"name":"Genentech, Inc., South San Francisco, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Janousek","sequence":"additional","affiliation":[{"name":"F. Hoffmann-La Roche Ltd, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Dr","given":"Gila","family":"Sellam","sequence":"additional","affiliation":[{"name":"Roche, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1879-8084","authenticated-orcid":false,"given":"Wojciech","family":"Jurczak","sequence":"additional","affiliation":[{"name":"Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2026,10,5]]},"container-title":["Blood Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2026035116\/2593887\/blood.2026035116.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2026035116\/2593887\/blood.2026035116.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:12:25Z","timestamp":1791220345000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/doi\/10.1182\/blood.2026035116\/571377\/Mosunetuzumab-and-Polatuzumab-Vedotin-as-First"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1182\/blood.2026035116","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]},"article-number":"blood.2026035116"}}