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What are next generation immunomodulatory drugs (IMiDs)?

A MyMyelomaTeam Member asked a question 💭
Lake Charles, LA

Next-generation immunomodulatory drugs (IMiDs), known as CELMoDs (Cereblon E3 Ligase Modulators), include iberdomide and mezigdomide. These novel agents bind cereblon with much higher affinity and potency than older IMiDs like lenalidomide or pomalidomide.Mechanism and AdvantagesHigher Potency: Induce rapid, deep degradation of target proteins (Ikaros and Aiolos).Cytotoxic Action: Shift from the predominantly cytostatic effects of traditional IMiDs to direct tumor cell death.Overcoming… read more

July 28
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MyMyelomaTeam

Great question! Next-generation IMiDs, called CELMoDs (Cereblon E3 Ligase Modulators), are an exciting evolution beyond traditional immunomodulatory drugs like lenalidomide (Revlimid) and pomalidomide (Pomalyst).

The two key agents being developed are:

- Iberdomide (CC-220) — currently in advanced clinical trials for Show Full Answer

Great question! Next-generation IMiDs, called CELMoDs (Cereblon E3 Ligase Modulators), are an exciting evolution beyond traditional immunomodulatory drugs like lenalidomide (Revlimid) and pomalidomide (Pomalyst).

The two key agents being developed are:

- Iberdomide (CC-220) — currently in advanced clinical trials for relapsed/refractory myeloma
- Mezigdomide (CC-92480) — being studied as an oral treatment in combination regimens What makes CELMoDs different from older IMiDs comes down to a few important advantages:

- Higher potency — They bind more strongly to their target, causing faster and deeper destruction of proteins that help myeloma cells survive
- Direct tumor cell death — Unlike older IMiDs that mainly slow cancer growth, CELMoDs can directly kill myeloma cells
- Overcoming resistance — They show promising activity even when myeloma has stopped responding to lenalidomide or pomalidomide
- Stronger immune activation — They more powerfully stimulate T-cells and natural killer (NK) cells to fight myeloma

These are still largely investigational, so discussing eligibility for clinical trials with a myeloma specialist would be the best next step if these options are of interest.

July 28

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