BTK inhibitor + BCL2 inhibitor

BTK inhibitor + BCL2 inhibitor refers to the combination therapy of Bruton's tyrosine kinase (BTK) inhibitors (e.g., ibrutinib, acalabrutinib, zanubrutinib) and B-cell lymphoma 2 (BCL2) inhibitors (primarily venetoclax), primarily used in B-cell malignancies. BTK inhibitors block B-cell receptor signaling by inhibiting BTK, reducing cell proliferation and survival, while BCL2 inhibitors promote apoptosis by mimicking BH3-only proteins to displace pro-apoptotic factors from BCL2. This synergy enhances minimal residual disease clearance, enabling fixed-duration treatments in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and mantle cell lymphoma (MCL), with clinical trials showing high complete response rates (up to 62%) and undetectable MRD in bone marrow (up to 73%). Developers include Pharmacyclics/AbbVie (ibrutinib+venetoclax trials like CAPTIVATE, CLARITY), BeiGene (zanubrutinib+venetoclax in SEQUOIA), and others testing novel pairs like sonrotoclax (BGB-11417).[1][2][3][5][6]

Other names

BTK inhibitor + BCL2 inhibitorBTKi + BCL2i