Researchers are reporting a major advance in multiple myeloma treatment with a new class of drugs called CELMoDs (cereblon E3 ligase modulators), including iberdomide and mezigdomide. These drugs are stronger than traditional IMiDs like Revlimid, killing cancer cells directly while also boosting the immune system by activating T-cells and Natural Killer cells. They also tend to cause fewer severe non-blood-related side effects.
The phase 3 EXCALIBER-RRMM trial is testing a combination of iberdomide, daratumumab, and dexamethasone in patients with early relapsed myeloma. Instead of waiting for long-term progression-free survival data, the trial uses minimal residual disease (MRD) at 9–12 months as a key marker, potentially speeding FDA approval and getting effective treatments to patients faster, with a decision expected by August 2026.
Beyond relapse treatment, CELMoDs are being studied for post-transplant maintenance and as partners for CAR T-cell and bispecific therapies. Early results suggest they may improve both the depth and durability of response compared with older IMiDs, offering hope for more effective and safer long-term myeloma care.