{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:14:41Z","timestamp":1789442081154,"version":"build-2803163510"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>B-cell maturation antigen (BCMA)-targeting therapies provide a new approach to treating multiple myeloma (MM). Alnuctamab (ALNUC) is a 2\u2009+\u20091 immunoglobulin G1-based bispecific antibody binding BCMA and CD3\u03b5 receptors on myeloma and T cells, respectively. CC-93269-MM-001 is a first-in-human, phase 1 dose escalation\/expansion study investigating ALNUC in relapsed\/refractory MM. Patients had \u22653 prior regimens, disease progression \u226460 days of last regimen, and were BCMA-directed therapy-na\u00efve. ALNUC was administered intravenously (IV) and subcutaneously (SC); however, SC was selected for further evaluation due to the more favorable safety profile. Ninety-five patients received ALNUC SC; at data cutoff, 44.2% remained on treatment and median follow-up was 8.0 months. The recommended phase 2 dose was 30\u2009mg. The most common treatment emergent adverse events (any grade\/grade 3\/4) were CRS (57.9%\/0%), and neutropenia (53.7%\/43.2%). Infections were also frequent (64.2%\/14.7%). ORR was 58.9% for all ALNUC SC-treated patients and 71.4% for the 30-mg cohort; 47\/95 (49.5%) were measurable residual disease (MRD) negative. Overall, the safety and efficacy of ALNUC SC were comparable to other BCMA-targeted therapies. These results support improved safety of SC versus IV, and corroborate a step-up dosing strategy to mitigate CRS. Importantly, a schedule that de-intensifies over time provides favorable toxicity that may be applicable to other bispecific engagers.<\/jats:p>","DOI":"10.1038\/s41375-025-02841-x","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T09:43:18Z","timestamp":1767778998000},"page":"481-490","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Alnuctamab, a bivalent B-cell maturation antigen-targeting T cell engager for patients with relapsed or refractory multiple myeloma: results from a phase 1, first-in-human study"],"prefix":"10.1038","volume":"40","author":[{"given":"Noffar","family":"Bar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4816-1607","authenticated-orcid":false,"given":"Craig C.","family":"Hofmeister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2390-1218","authenticated-orcid":false,"given":"Maria-Victoria","family":"Mateos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7715-4548","authenticated-orcid":false,"given":"Markus","family":"Hansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8248-2343","authenticated-orcid":false,"given":"Laura","family":"Paris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swathi","family":"Namburi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paz","family":"Ribas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1709-9492","authenticated-orcid":false,"given":"Armando","family":"Santoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5236-7785","authenticated-orcid":false,"given":"Paula","family":"Rodriguez-Otero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Creignou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Kiesel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Gaudy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan G.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samah","family":"Zarif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh G.","family":"Shelat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Burgess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Godwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5362-2469","authenticated-orcid":false,"given":"Luciano J.","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"2841_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2021.100808","volume":"49","author":"K Ramasamy","year":"2021","unstructured":"Ramasamy K, Gay F, Weisel K, Zweegman S, Mateos MV, Richardson P. Improving outcomes for patients with relapsed multiple myeloma: challenges and considerations of current and emerging treatment options. Blood Rev. 2021;49:100808.","journal-title":"Blood Rev"},{"key":"2841_CR2","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1056\/NEJMoa2024850","volume":"384","author":"NC Munshi","year":"2021","unstructured":"Munshi NC, Anderson LD Jr, Shah N, Madduri D, Berdeja J, Lonial S, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384:705\u201316.","journal-title":"N Engl J Med"},{"key":"2841_CR3","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1200\/JCO.22.00842","volume":"41","author":"T Martin","year":"2023","unstructured":"Martin T, Usmani SZ, Berdeja JG, Agha M, Cohen AD, Hari P, et al. Ciltacabtagene autoleucel, an anti-B-cell maturation antigen chimeric antigen receptor T-cell therapy, for relapsed\/refractory multiple myeloma: CARTITUDE-1 2-year follow-up. 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TM receives grants or contracts from Funding for Research to University (UCSF); CH received grants or contracts from Sanofi, BMS, Janssen, AbbVie, received royalties or licenses from Recursion pharmaceuticals, received consulting fees from AbbVie, Janssen; MVM received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Johnson & Johnson, BMS, Amgen, Sanofi, GSK, Pfizer, AbbVie, Astra Zeneca, Stemline Menarini, Oncopeptide, Regeneron; MH received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Janssen, Bristol Myers Squibb, Takeda, Celgene, GlaxoSmithKline, and Oncopeptides; LP received consulting fees from Johnson & Johnson, received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Johnson & Johnson, Bristol Myers Squibb, Takeda, Amgen, GSK, received support for attending meetings and\/or travel from AbbVie, Johnson & Johnson, Takeda, participated on a Data Safety Monitoring Board or Advisory Board for Johnson & Johnson, Bristol Myers Squibb, Takeda, Amgen, GSK, Sanofi, Menarini; SN received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Targeted Oncology, and participated on a Data Safety Monitoring Board or Advisory Board for Bristol Myers Squibb, Johnson & Johnson, GSK, Pfizer, and Sanofi; PR declared no COIs; AS received consulting fees from Sanofi, Incyte, received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events Takeda, BMS, Roche, AbbVie, Amgen, Celgene, Servier, Gilead, AstraZeneca, Pfizer, Arqule, Lilly, Sandoz, Eisai, Novartis, Bayer, MSD, Beigene, participated on a Data Safety Monitoring Board or Advisory Board for BMS, Servier, Gliead, Pfizer, Eisai, Bayer, MSD; PR-O received consulting fees from BMS, Johnson & Johnson, GSK, Pfizer, Regeneron, AstraZeneca, Roche, AbbVie, Sanofi, H3 Biomedicine, Menarini Stemlin, Oncopeptides, received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from BMS, Johnson & Johnson, GSK, Pfizer, participated on a Data Safety Monitoring Board or Advisory Board for BMS, Johnson & Johnson, Regeneron; MC declared no COIs; JC declared no COIs; CC is a BMS employee and owns BMS stock; BK is a BMS employee and owns patents and stock from BMS; AG is a BMS employee and owns BMS stock; EGT is a BMS employee and owns BMS stock; YS is a BMS employee and owns BMS stock; SZ declared no COIs; KS is a BMS employee and owns BMS stock; SGS is a BMS employee and owns BMS stock; MRB is a BMS employee and owns patents and stock from BMS; LJC received grants or contracts from Amgen, Johnson & Johnson, Pfizer, Genetech, Caribou, and AstraZeneca; received consulting fees from Amgen, Johnson & Johnson, Pfizer, Genetech, Caribou, AstraZeneca, BMS, and Sanofi; and received honoraria from Amgen, Johnson & Johnson, Pfizer, Beigene, BMS, Sanofi, and Adaptive Biotechnologies.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}