venetoclax + bortezomib + dexamethasone

**Venetoclax + bortezomib + dexamethasone** is a combination therapy investigated primarily for the treatment of **relapsed or refractory multiple myeloma**. Venetoclax is a selective, orally bioavailable small molecule inhibitor of BCL-2, an anti-apoptotic protein, which induces apoptosis in malignant plasma cells. Bortezomib is a proteasome inhibitor that can indirectly inhibit another anti-apoptotic protein, MCL-1, by stabilizing the MCL-1–neutralizing protein NOXA. Dexamethasone is a corticosteroid that can upregulate pro-apoptotic proteins, further sensitizing malignant cells to apoptosis. The rationale for this combination is the simultaneous inhibition of key survival pathways in myeloma cells (BCL-2 and MCL-1) and enhancement of pro-apoptotic signaling, leading to increased cell death in malignant plasma cells[1][3][6][7]. This regimen has shown promising efficacy and an acceptable safety profile in clinical trials, especially in patients with high BCL-2 expression and/or t(11;14) cytogenetic aberration[1][2][7].