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Updated: Jun 20, 2026
10:44
Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma
Martha Q Lacy1, Suzanne R Hayman, Morie A Gertz
1Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. lacy.martha@mayo.edu
Summary
Pomalidomide combined with low-dose dexamethasone shows high efficacy in treating relapsed multiple myeloma. This combination therapy achieved significant response rates, even in patients refractory to other novel agents.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Thalidomide and lenalidomide are established immunomodulatory drugs (IMiDs) for multiple myeloma.
- Pomalidomide is a novel IMiD with potent in vitro activity.
- Relapsed or refractory multiple myeloma requires new therapeutic strategies.
Purpose of the Study:
- To evaluate the efficacy and safety of pomalidomide plus low-dose dexamethasone in relapsed/refractory multiple myeloma.
- To report the findings of the first phase II clinical trial for this combination therapy.
Main Methods:
- A phase II trial involving 60 patients with relapsed or refractory multiple myeloma.
- Oral administration of pomalidomide (2 mg daily) and dexamethasone (40 mg daily) in a 28-day cycle.
- Response assessment based on International Myeloma Working Group criteria.
Main Results:
- A 63% confirmed response rate, including 5% complete responses.
- Effective responses observed in patients refractory to lenalidomide (40%), thalidomide (37%), and bortezomib (60%).
- High response rates (74%) in patients with high-risk cytogenetic or molecular markers; primary toxicity was myelosuppression.
Conclusions:
- Pomalidomide and low-dose dexamethasone combination is highly active in relapsed multiple myeloma.
- This regimen demonstrates significant efficacy in patients refractory to prior novel agents.
- The combination offers a promising treatment option for challenging multiple myeloma cases.
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