bortezomib + thalidomide + lenalidomide

**Bortezomib + thalidomide + lenalidomide** is an experimental triple combination regimen for multiple myeloma, combining a proteasome inhibitor (bortezomib), with two immunomodulatory drugs (IMiDs: thalidomide and lenalidomide). Bortezomib inhibits the 26S proteasome, leading to accumulation of ubiquitinated proteins and apoptosis in myeloma cells. Thalidomide and lenalidomide bind cereblon (CRBN), promoting ubiquitination and degradation of transcription factors Ikaros (IKZF1) and Aiolos (IKZF3), inhibiting myeloma cell growth, angiogenesis, and immune modulation. This regimen has been explored in relapsed/refractory settings but lacks a standardized protocol or approval due to overlapping toxicities like neuropathy, cytopenias, and thromboembolism; it is not a commercially available fixed-dose product.[1]