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This is a combination therapy consisting of a Bruton tyrosine kinase (BTK) inhibitor and anti-CD19 chimeric antigen receptor (CAR) T cells. The BTK inhibitors commonly used in this context include ibrutinib, acalabrutinib, zanubrutinib, and orelabrutinib. Anti-CD19 CAR T cell therapies are genetically engineered autologous or allogeneic T cells that express a synthetic receptor targeting the CD19 antigen on B-cells. The rationale for combining these agents is based on evidence that BTK inhibitors can modulate the tumor microenvironment and enhance the function of CAR-T cells by reducing exhaustion, improving expansion and persistence, increasing Th1 differentiation, and potentially mitigating cytokine release syndrome. This combination has been studied primarily in relapsed/refractory B-cell malignancies such as chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL). Clinical trials have demonstrated safety and promising efficacy with durable remissions in patients who have not achieved complete response with either agent alone[1][2][6][7][8].
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