Related Experiment Video

Updated: Jan 12, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

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Mezigdomide for multiple myeloma: a focus on phase 2 trial data

Clifton C Mo1, Yuxin Liu1, Omar Nadeem1

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA, USA.

Expert Opinion on Emerging Drugs
|October 30, 2025
PubMed
Abstract

Insights

Mezigdomide, a novel cereblon E3 ligase modulator, shows promising clinical efficacy in early trials for relapsed/refractory multiple myeloma (MM). It demonstrates superior potency and synergistic effects, offering new hope for difficult-to-treat MM patients.

Area of Science:

  • Hematology
  • Oncology
  • Pharmacology

Background:

  • The treatment landscape for multiple myeloma (MM) has significantly advanced, with current standards including combinations of CD38 monoclonal antibodies, proteasome inhibitors, and immunomodulatory drugs.
  • Novel targeted and immune-based therapies are increasingly integrated into earlier treatment lines.
  • There remains a critical need for innovative therapeutic options to enhance outcomes in both newly diagnosed and relapsed/refractory multiple myeloma (RRMM).

Purpose of the Study:

  • To review preclinical and clinical data on mezigdomide, a cereblon E3 ligase modulator.
  • To assess the potential of mezigdomide as a novel therapeutic agent for RRMM.

Main Methods:

  • Literature search of PubMed, congress abstracts (last 5 years), and ClinicalTrials.gov.
  • Inclusion of studies using terms 'mezigdomide' or 'CC-92480' and 'myeloma'.

Main Results:

  • Mezigdomide exhibits higher cereblon binding affinity and greater protein degradation potency than existing immunomodulatory drugs.
  • Early-phase clinical trials indicate notable efficacy, even in poor-prognosis triple-class-refractory disease.
  • Preclinical studies show synergistic effects with standard-of-care therapies, and clinical evaluation in combinations is ongoing.

Conclusions:

  • Mezigdomide represents a promising novel therapeutic agent for RRMM.
  • Its unique mechanism and demonstrated efficacy suggest potential to improve outcomes in challenging MM settings.
  • Further clinical investigation, including combination therapies, is warranted.
Keywords:
CELMoDcereblonimmunomodulatormezigdomidemultiple myelomaphase 1/2refractoryrelapsed

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