venetoclax + ibrutinib

venetoclax + ibrutinib is a combination therapy being evaluated for the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). This specific regimen, investigated by The First Affiliated Hospital with Nanjing Medical University, utilizes venetoclax as a consolidation therapy for patients who have achieved a response but remain minimal residual disease (MRD) positive after at least six months of monotherapy with a Bruton's tyrosine kinase (BTK) inhibitor such as ibrutinib. Venetoclax is a selective, orally bioavailable small molecule that inhibits B-cell lymphoma 2 (BCL-2), an anti-apoptotic protein; by binding to BCL-2, venetoclax displaces pro-apoptotic proteins and restores the process of apoptosis in malignant B cells. Ibrutinib is a small molecule that forms a covalent bond with a cysteine residue (Cys481) in the BTK active site, leading to irreversible inhibition of the enzyme. BTK is a critical signaling kinase in the B-cell receptor pathway, and its inhibition disrupts the survival, proliferation, and migration of CLL cells. The combination is designed to provide a synergistic effect, where BTK inhibition mobilizes leukemia cells from protective lymphoid niches into the peripheral blood, making them more susceptible to BCL-2-mediated apoptosis induced by venetoclax.

Brand names

ImbruvicaVenclexta

Other names

Venetoclax plus ibrutinibIbrutinib and venetoclax combination