T cell characteristics impact response and resistance to T cell-redirecting bispecific antibodies in multiple myeloma

Bispecific antibodies (BsAbs) directed against B-cell maturation antigen (BCMA; teclistamab) or the orphan G protein-coupled receptor GPRC5D (talquetamab) induce deep and durable responses in heavily pretreated MM patients. However, mechanisms underlying primary and acquired resistance remain poorly...

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Published in:Clinical cancer research 2024-07, Vol.30 (14), p.3006-3022
Main Authors: Verkleij, Christie P M, O'Neill, Chloe A, Broekmans, Marloes E C, Frerichs, Kristine A, Bruins, Wassilis S C, Duetz, Carolien, Kruyswijk, Sandy, Baglio, Serena R, Skerget, Sheri, Montes de Oca, Rocio, Zweegman, Sonja, Verona, Raluca I, Mutis, Tuna, van de Donk, Niels W C J
Format: Article
Language:English
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Summary:Bispecific antibodies (BsAbs) directed against B-cell maturation antigen (BCMA; teclistamab) or the orphan G protein-coupled receptor GPRC5D (talquetamab) induce deep and durable responses in heavily pretreated MM patients. However, mechanisms underlying primary and acquired resistance remain poorly understood. The anti-MM activity of teclistamab and talquetamab was evaluated in bone marrow (BM) samples from MM patients. T-cell phenotype and function were assessed in BM/peripheral blood samples obtained from MM patients who were treated with these BsAbs. In ex vivo killing assays with 41 BM samples from BsAb-naïve MM patients, teclistamab- and talquetamab-mediated MM lysis were strongly correlated (r=0.73, P
ISSN:1078-0432
1557-3265
1557-3265
DOI:10.1158/1078-0432.CCR-23-3333