thalidomide + lenalidomide

A fixed-combination concept of two immunomodulatory imide drugs consisting of thalidomide and lenalidomide, both oral small-molecule cereblon E3 ligase modulators with antineoplastic, anti-angiogenic, and immunomodulatory activity. Thalidomide and lenalidomide bind cereblon to alter substrate specificity of the CRL4CRBN E3 ubiquitin ligase, promoting degradation of transcription factors such as IKZF1 and IKZF3, leading to direct myeloma cell death and immune activation. Both are indicated individually in multiple myeloma regimens, often with corticosteroids; lenalidomide is generally preferred due to improved efficacy/tolerability, while thalidomide use is limited by neuropathy and teratogenicity. Both require REMS due to severe teratogenic risk.[6][4][5][2]