S187: Updated Phase 1/2 Data of Safety and Efficacy of Ct103a, Fully Human Bcma-Directed Car T Cells, in Relapsed/Refractory Multiple Myeloma

CD38 and B-cell maturation antigens (BCMAs) are prevalently expressed on neoplastic plasma cells in multiple myeloma (MM), making them ideal therapeutic targets. Anti-CD38 monoclonal antibodies, such as approved daratumumab and isatuximab, are currently the milestone in MM treatment because they induce plasma cell apoptosis and kill through several mechanisms, including antibody-dependent cellular cytotoxicity or phagocytosis. BCMA is considered an excellent target in MM, and three different therapeutic strategies are either already available in clinical practice or under investigation: antibody–drug conjugates, such as belantamab-mafodotin; bispecific T cell engagers; and chimeric antigen receptor-modified T cell therapies. Despite the impressive clinical efficacy of these new strategies in the treatment of newly diagnosed or multi-refractory MM patients, several mechanisms of resistance have already been described, including antigen downregulation, the impairment of antibody-dependent cell cytotoxicity and phagocytosis, T- and natural killer cell senescence, and exhaustion. In this review, we summarize the current knowledge on the mechanisms of action and resistance of anti-CD38 and anti-BCMA agents and their clinical efficacy and safety.

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Innovative Anti-CD38 and Anti-BCMA Targeted Therapies in Multiple Myeloma: Mechanisms of Action and Resistance

Novellis

Fontana

Giudice

et al. 2022

IJMS

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S187: Updated Phase 1/2 Data of Safety and Efficacy of Ct103a, Fully Human Bcma-Directed Car T Cells, in Relapsed/Refractory Multiple Myeloma

Abstract: Background: Background: CT103A, a fully human BCMA-directed CAR-T therapy, showed excellent safety and promising efficacy in the ongoing phase 1/2 FUMANBA-1 study (ChiCTR1800018137, NCT05066646) in patients with relapsed/refractory multiple myeloma (Wang, ASH, 2021).

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Innovative Anti-CD38 and Anti-BCMA Targeted Therapies in Multiple Myeloma: Mechanisms of Action and Resistance

Innovative Anti-CD38 and Anti-BCMA Targeted Therapies in Multiple Myeloma: Mechanisms of Action and Resistance

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