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February 9, 2026European Journal Of HaematologyOpen Access

Targeting Ikaros and Aiolos: Next‐Generation Cereblon E3 Ligase Modulators in MM

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Authors

MAMaria Eugenia AlvaroEMEnrica Antonia MartinoSCSantino Caserta

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Overview

This review explores next-generation cereblon E3 ligase modulators in multiple myeloma, highlighting their therapeutic potential and future directions.

Key Points

  • The aim is to evaluate next-generation cereblon E3 ligase modulators designed to overcome drug resistance in multiple myeloma.
  • Review of preclinical and clinical trials on cereblon E3 ligase modulators Iberdomide and Mezigdomide.
  • Analysis of their mechanisms of action focusing on Ikaros and Aiolos degradation.
  • Assessment of pharmacodynamic properties and their differentiation from traditional immunomodulatory drugs.
  • Iberdomide and Mezigdomide show enhanced degradation of Ikaros and Aiolos, potentially overcoming resistance.
  • These CELMoDs have demonstrated improved immune effector responses in preclinical studies.
  • Evidence suggests potential integration with monoclonal antibodies and T-cell-directed therapies in ongoing trials.

Cite This Study

Alvaro et al. (2026) studied this question.

synapsesocial.com/papers/698979f5f0ec2af6756e819chttps://doi.org/10.1111/ejh.70134
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