This issue could be overcome by either hijacking two different E3 ligases, CRBN and VHL, or a PROTAC, such as YKL-06-102, that simultaneously targets IKZF1, IKZF3, and CDK6, achieving intramolecular synergistic effects even in IMiD-insensitive multiple myeloma cells. Here, IKZF1 is linked to plasma cell myeloma.