{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T03:12:20Z","timestamp":1785208340764,"version":"3.55.0"},"reference-count":5,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"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. Oncol."],"abstract":"<jats:p>The management of relapsed\/refractory multiple myeloma with true extramedullary disease (EMD) remains a critical challenge. The phase 2 RedirecTT-1 study evaluated the combination of two bispecific antibodies, talquetamab (anti-GPRC5D) and teclistamab (anti-BCMA), in this high-risk population. While the reported overall response rate of 79% and 12-month progression\u2212free survival of 61% are promising, a balanced interpretation requires caution. The single\u2212arm design, short follow\u2212up (12.6 months), and indirect comparisons with CAR\u2212T therapy preclude definitive conclusions about comparative effectiveness. Notably, grade 3\u20134 infections occurred in 31% of patients, with five treatment\u2212related deaths \u2013 a toxicity burden that may limit real\u2212world implementation outside specialized centers. Responses were observed after prior BCMA\u2212directed CAR\u2212T therapy, but heterogeneity within this subgroup (time from CAR\u2212T to progression ranging from 98 to 1030 days) tempers enthusiasm for universal sequencing strategies. Key unresolved questions include optimal sequencing with CAR\u2212T, mechanisms of resistance, predictive biomarkers, and the feasibility of delivering this intensive regimen in routine practice. This commentary argues that dual bispecific therapy is a potent but still investigational option for EMD, and its definitive positioning requires randomized data and head\u2212to\u2212head comparisons.<\/jats:p>","DOI":"10.3389\/fonc.2026.1822293","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T04:39:43Z","timestamp":1776227983000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Beyond dual targeting: redefining the treatment horizon for true extramedullary myeloma? \u2013 a critical appraisal"],"prefix":"10.3389","volume":"16","author":[{"given":"Qinghua","family":"Ke","sequence":"first","affiliation":[{"name":"Department of Chemoradiotherapy, The First People\u2019s Hospital of Jingzhou","place":["Jingzhou, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqiong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Chemoradiotherapy, The First People\u2019s Hospital of Jingzhou","place":["Jingzhou, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1038\/s41408-025-01330-9","article-title":"Activity of CAR-T cells and bispecific antibodies in multiple myeloma with extramedullary involvement","volume":"15","author":"Steinhardt","year":"2025","journal-title":"Blood Cancer J"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-23-3333","article-title":"T-cell characteristics impact response and resistance to T-cell-redirecting bispecific antibodies in multiple myeloma","volume":"30","author":"Verkleij","year":"2024","journal-title":"Clin Cancer Res"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2406536","article-title":"Talquetamab plus\u00a0teclistamab in relapsed or refractory multiple myeloma","volume":"392","author":"Cohen","year":"2025","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2025016490","article-title":"Immunoglobulin prophylaxis should be initiated after bispecific antibody therapy in multiple myeloma, regardless of IgG levels","volume":"9","author":"Banerjee","year":"2025","journal-title":"Blood Adv"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.beha.2025.101649","article-title":"Bispecific T-cell engager therapy for multiple myeloma","volume":"38","author":"Cirstea","year":"2025","journal-title":"Best Pract Res Clin Hematol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1822293\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T04:39:51Z","timestamp":1776227991000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1822293\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,15]]},"references-count":5,"alternative-id":["10.3389\/fonc.2026.1822293"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1822293","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,15]]},"article-number":"1822293"}}