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Although the T\u2010cell\u2010engaging bispecific antibody talquetamab is currently the only approved anti\u2010GPRC5D therapy, numerous promising agents are undergoing clinical evaluation. While anti\u2010GPRC5D chimeric antigen receptor T cells show potential, this review focuses specifically on T\u2010cell\u2010engaging bispecific and trispecific antibodies. We highlight how GPRC5D differs clinically from B\u2010cell maturation antigen, explore mechanisms of resistance, discuss novel therapeutic strategies including combination regimens and talquetamab as bridging therapy to chimeric antigen receptor T cells, and review key investigational T\u2010cell engagers currently in development.<\/jats:p>","DOI":"10.1002\/cncr.70597","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:05:22Z","timestamp":1788239122000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["GPRC5D\u2010targeting bispecific and trispecific antibodies in multiple myeloma: Current evidence and emerging strategies"],"prefix":"10.1002","volume":"132","author":[{"given":"Darren","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Medicine University of California  San Francisco California 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Available from:https:\/\/www.fda.gov\/drugs\/resources\u2010information\u2010approved\u2010drugs\/fda\u2010grants\u2010accelerated\u2010approval\u2010talquetamab\u2010tgvs\u2010relapsed\u2010or\u2010refractory\u2010multiple\u2010myeloma"},{"key":"e_1_2_11_25_1","unstructured":"van deDonkNW PopatR Faiman.B et\u00a0al.Early resolution of talquetamab oral side effects in relapsed\/refractory multiple myeloma (RRMM): updated Waterless Empirical Taste Test (WETT) and patient reported outcomes (PRO) data from TALISMAN. Poster presented at: European Hematology Association (EHA);Jun 11\u201314 2026;Milan ItalyAbstract PF790 (EHA\u20102432)."},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408\u2010025\u201001342\u20105"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022015956"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2025029360"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102015\u201012\u2010687749"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102025\u20102282"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2406536"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41409\u2010025\u201002593\u20103"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2514752"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102025\u201091"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102025\u20105831"},{"key":"e_1_2_11_36_1","article-title":"MBS314, a GPRC5DxBCMAxCD3 trispecific antibody. 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Oral presentation at International Myeloma Society 20th Annual Meeting and Exposition;September 27\u201330 2023.","DOI":"10.1016\/S2152-2650(23)01572-0"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102024\u2010201960"},{"key":"e_1_2_11_42_1","unstructured":"Leads Biolabs' GPRC5D\/CD3 Bispecific T\u2010Cell Engager LBL\u2010034 Earns FDA Fast Track Designation\u2014Accelerating Launch of Potential Best\u2010in\u2010Class Therapy for Relapsed\/Refractory Multiple Myeloma. 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