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A dual-agent antineoplastic combination of the proteasome inhibitor bortezomib and the immunomodulatory drug lenalidomide. Bortezomib inhibits the 26S proteasome’s chymotrypsin-like activity, leading to accumulation of ubiquitinated proteins, disruption of NF-κB signaling, cell cycle arrest, and apoptosis in myeloma cells. Lenalidomide is an immunomodulatory agent that binds cereblon, altering the CRL4CRBN E3 ubiquitin ligase to induce targeted degradation of transcription factors Ikaros (IKZF1) and Aiolos (IKZF3), resulting in direct myeloma cell cytotoxicity, T-cell and NK-cell activation, and anti-angiogenic effects. The combination is widely used in multiple myeloma regimens (commonly with dexamethasone as VRd), across newly diagnosed, relapsed/refractory, induction, consolidation, and maintenance settings.
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