GCKi and iberdomide show synergistic anti-MM effects on primary MM. (A) Primary MM samples (RAS^WT, n = 12; RAS^Mut, n = 3) were cocultured with bone marrow stromal cells and treated with TL4-12 at the indicated concentrations for 5 days. Cell viability rate was analyzed by MTS. (B) Primary MM cell viability inhibition rate by TL4-12 at 8 μM were compared between RAS^WT and RAS^Mut. (C) NRAS^G61K primary CD138⁺ MM cells cocultured with bone marrow stromal cells were treated with TL4-12 and iberdomide at the indicated concentrations for 4 days. Cell viability was analyzed by MTS. (D) RAS^WT plasma CD138⁺ cells were treated with TL4-12 and iberdomide at the indicated concentrations for 4 days. Cell apoptosis was detected by flow cytometry after Annexin V and 7-AAD staining.