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General Updates | GPRC5D-directed therapies in myeloma: mechanisms of resistance & strategies to overcome resistance
In this discussion, Charlotte Pawlyn, BA, MBBChir, MRCP, PhD, FRCPath, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK, Omar Nadeem, MD, Dana-Farber Cancer Institute, Boston, MA, and Sridevi Rajeeve, MD, Memorial Sloan Kettering Cancer Center, New York City, NY, examine the evolving role of GPRC5D-targeted therapies in multiple myeloma, highlighting strong response rates with agents such as talquetamab and emerging modalities including CAR T-cells, bispecifics, and trispecific antibodies. The panel emphasizes the growing importance of diagnostics for assessing antigen expression and guiding sequencing decisions, while noting current limitations in standardization and accessibility. Additionally, the experts discuss key resistance mechanisms such as antigen loss and T-cell exhaustion, and explore future strategies to improve durability of response and overcome resistance.
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