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What factors contribute to resistance to BCMA-targeted CAR T-cell therapies in multiple myeloma?

Mar 28, 2024
Learning objective: After reading this article, learners will be able to cite a new clinical development in multiple myeloma.

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During the 6th European CAR T-cell Meeting of the European Hematology Association and European Society for Blood and Marrow Transplantation, the Multiple Myeloma Hub spoke to Paola Neri, University of Calgary, Calgary, CA. We asked, What factors contribute to resistance to B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T-cell therapies in multiple myeloma?

What factors contribute to resistance to BCMA-targeted CAR T-cell therapies in multiple myeloma?

In this interview, Paola Neri discusses the factors associated with either a lack of response to BCMA-targeted CAR T-cell therapies or loss of response over time, going on to offer insight into the management strategies for these patients. Neri highlights key issues of antigen escape, mutation of BCMA, as well as T-cell exhaustion; she closes with the additional considerations required for difficult-to-treat forms of multiple myeloma, such as extramedullary disease.1,2,3

  1. Lee H, Ahn S, Maity R, et al. Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma. Nat Med. 2023;29(9):2295-2306. DOI: 1038/s41591-023-02491-5.
  2. Friedrich M, Neri P, Kehl N, et al. The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients. Cancer Cell. 2023;41(4):711-725.e6. DOI: 1016/j.ccell.2023.02.008.
  3. Dhodapkar K, Cohen A, Kaushal A, et al. Changes in bone marrow tumor and immune cells correlate with durability of remissions following BCMA CAR T therapy in myeloma. Blood Cancer Discov. 2022;3(6):490-501. DOI: 1158/2643-3230.BCD-22-0018.

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