CC-92480 Enhances Cell-Autonomous Cytotoxicity through Blockade of G 2/M Transition When Combined with Bortezomib/Dexamethasone in Pre-Clinical Multiple Myeloma

Background: Pomalidomide (POM) is an established agent in relapsed/refractory (R/R) multiple myeloma (MM). CC-92480, a novel cereblon E3 ligase modulator (CELMoD ®) agent, is being investigated in R/R MM patients in combination with the proteasome inhibitor (PI) bortezomib (BTZ) and steroid dexamethasone (DEX) (NCT03374085/NCT03989414). Previously, we showed mechanistic synergy of POM/BTZ/DEX in MM cell line models (Bjorklund et al). Here we analyzed the cell autonomous cytotoxic activities of CC-92480 or POM alone and in combination with BTZ/DEX to compare and differentiate their mechanisms of action (MOA).