Resistance to immunomodulatory drugs in multiple myeloma: the cereblon pathway and beyond.
Teoh PJ., Koh MY., Mitsiades C., Gooding S., Chng WJ.
Acquired resistance to immunomodulatory drugs (IMiD) remains a significant unmet need in the treatment landscape of multiple myeloma (MM). The cereblon (CRBN) pathway-dependent mechanisms are known to be vital contributors to IMiD resistance; however, they may account for only a small proportion. Recent research has unveiled additional mechanisms of acquired IMiD resistance that are independent of the CRBN pathway. In this review, we provide a comprehensive overview of the existing work on IMiD resistance in MM, focusing specifically on the emerging evidence of CRBN pathway-independent mechanisms. Finally, we discuss the plausible actionable strategies and outlook for IMiD-based therapies moving forward.