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Mezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma.
Paul G Richardson1, Suzanne Trudel1, Rakesh Popat1
1From Dana-Farber Cancer Institute, Boston (P.G.R.); the Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto (S.T.), and Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB (N.J.B.) - both in Canada; NIHR UCLH Clinical Research Facility, University College London Hospitals NHS Foundation Trust (R.P.), the Institute of Cancer Research (C.P.), and the Royal Marsden NHS Foundation Trust (C.P.), London, and the Department of Clinical Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford (K.R.) - all in the United Kingdom; University Hospital of Salamanca/IBSAL, Salamanca (M.-V.M.), the Department of Hematology, Hospital 12 de Octubre, Department of Medicine, School of Medicine, Complutense University, H12O-CNIO Clinical Research Unit, CIBERONC, Madrid (J.M.-L.), Hospital Universitari La Fe, Valencia (M.A.), Institut Català d'Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona (A.O.), Clínica Universidad de Navarra, CIMA, IDISNA, CIBERONC, Pamplona (P.R.O.), and Hospital San Pedro de Alcántara, Cáceres (I.C.-A.) - all in Spain; the Department of Hematology, Rigshospitalet, Copenhagen (A.J.V.); St. Vincent's Hospital Melbourne, University of Melbourne, Melbourne, VIC, Australia (H.Q.); the Department of Lymphoma and Myeloma, University of Texas M.D. Anderson Cancer Center, Houston (R.Z.O.); Winship Cancer Institute, Emory University, Atlanta (S. Lonial); Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope, Duarte, CA (C.K.); Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea (K.K.); Sarah Cannon Research Institute, Nashville (J.G.B.); Celgene International, a Bristol-Myers Squibb Company, Boudry, Switzerland (A.S., T.P.); and Bristol Myers Squibb, Princeton, NJ (J.P., S. Li, J.G., L.W., M.L., D.W.P., M.A., P.M., J.K., M.P.).
Mezigdomide combined with dexamethasone shows promise for treating relapsed and refractory multiple myeloma. This novel oral therapy demonstrated significant overall response rates in heavily pretreated patients.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Multiple myeloma remains an incurable hematologic malignancy despite advancements.
- Mezigdomide, a novel cereblon E3 ubiquitin ligase modulator, exhibits potent anti-myeloma activity in preclinical studies.
- It shows efficacy in models resistant to existing therapies like lenalidomide and pomalidomide.
Purpose of the Study:
- To evaluate the safety, pharmacokinetics, and efficacy of oral mezigdomide in combination with dexamethasone.
- To determine the recommended phase 2 dose and schedule for mezigdomide plus dexamethasone.
- To assess the overall response rate and survival outcomes in patients with relapsed and refractory multiple myeloma.
Main Methods:
- A phase 1-2 study involving dose-escalation (phase 1) and dose-expansion (phase 2) cohorts.
- Patients received oral mezigdomide and dexamethasone in 28-day cycles.
- Safety, tolerability, pharmacokinetics, and efficacy (overall response, duration of response, progression-free survival) were assessed.
Main Results:
- The recommended phase 2 dose was determined to be 1.0 mg of mezigdomide once daily for 21 days per cycle.
- In phase 2, 101 heavily pretreated patients with triple-class-refractory multiple myeloma were enrolled.
- An overall response was observed in 41% of patients, with a median duration of response of 7.6 months and median progression-free survival of 4.4 months.
Conclusions:
- The all-oral combination of mezigdomide and dexamethasone demonstrates promising efficacy in patients with heavily pretreated multiple myeloma.
- Treatment-related adverse events were primarily myelotoxic effects, mostly reversible.
- This combination represents a potential new therapeutic option for patients with relapsed and refractory multiple myeloma.
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