The Multiple Myeloma Hub spoke with Paul Richardson, Dana-Farber Cancer Institute, Boston, US. We asked about the mechanism of action and immunomodulatory activity of cereblon E3 ligase modulators (CELMoDs) in multiple myeloma.
During this interview, Richardson discusses how CELMoDs target the cereblon E3 ubiquitin ligase complex to induce selective protein degradation and immunomodulatory effects. Richardson explains how CELMoDs, such as iberdomide and mezigdomide, differ structurally and functionally from earlier immunomodulatory drugs (IMiDs), resulting in enhanced substrate degradation and immune activation. He notes that anti-MM activity has also been demonstrated in combination with established myeloma therapies. Richardson also discusses translational and preclinical findings on the ability of CELMoDs to overcome resistance and modulate the tumor microenvironment.
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