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This is a **combination regimen** of three anticancer agents for relapsed or refractory multiple myeloma, uniting the following drugs: - **Talquetamab**, a first-in-class GPRC5D-directed bispecific antibody that binds to both CD3 on T cells and GPRC5D on myeloma cells, driving T-cell-mediated cytotoxicity against myeloma cells. - **Daratumumab**, a CD38-directed monoclonal antibody that induces direct apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC). It also depletes immunosuppressive cell populations like Tregs, further potentiating antitumor responses. - **Carfilzomib**, a proteasome inhibitor that irreversibly inhibits the chymotrypsin-like activity of the 20S proteasome, causing accumulation of ubiquitinated proteins and apoptosis of malignant plasma cells. The rationale for this combination is supported by their complementary mechanisms: talquetamab elicits T cell cytotoxicity independent of BCMA, daratumumab enhances immune response and depletes immunosuppressive cells, and carfilzomib blocks proteasomal degradation pathways crucial for myeloma cell survival. Each is developed primarily by Janssen (Johnson & Johnson) for talquetamab and daratumumab, and Onyx (Amgen) for carfilzomib. The combination is under investigation, primarily in advanced relapsed/refractory multiple myeloma, but this specific triple regimen is experimental.
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