Pomalidomide plus low‐dose dexamethasone in relapsed refractory multiple myeloma after lenalidomide treatment failure
Open accessAbstract
Summary: Patients with relapsed/refractory multiple myeloma (RRMM) for whom the benefits of lenalidomide have been exhausted in early treatment lines need effective therapies. In cohort A of the phase 2 MM‐014 trial, we examined the safety and efficacy of pomalidomide plus low‐dose dexamethasone immediately after lenalidomide‐based treatment failure in patients with RRMM and two prior lines of therapy. Pomalidomide 4 mg was given on days 1 to 21 of 28‐day cycles. Dexamethasone 40 mg (20 mg for patients aged >75 years) was given on days 1, 8, 15 and 22 of 28‐day cycles. The primary endpoint was overall response rate (ORR), and secondary endpoints included progression‐free survival (PFS), overall survival (OS) and safety. The intention‐to‐treat population comprised 56 patients; all received prior lenalidomide (87·5% lenalidomide refractory) and 39 (69·6%) received prior bortezomib. ORR was 32·1% (28·2% in the prior‐bortezomib subgroup). Median PFS was 12·2 months (7·9 months in the prior‐bortezomib subgroup). Median OS was 41·7 months (38·6 months in the prior‐bortezomib subgroup). The most common grade 3/4 treatment‐emergent adverse events were anaemia (25·0%), pneumonia (14·3%) and fatigue (14·3%). These findings support earlier sequencing of pomalidomide‐based therapy in lenalidomide‐pretreated patients with RRMM, including those who have become refractory to lenalidomide. Trial registration: www.ClinicalTrials.gov identifier NCT01946477.
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In vitro studies support the hypothesis that thalidomide analogues synergize with dexamethasone, proteasome inhibitors, histone deacetylase inhibitors and a variety of other agents.
“Data from a number of in vitro studies support the hypothesis that thalidomide analogues synergize with dexamethasone49,50, proteasome inhibitors51,52, histone deacetylase inhibitors53,54 and a variety of other agents”
From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [49]
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- Authors
- Siegel, D. S., Schiller, G. J., Song, K. W., Agajanian, R., Stockerl‐Goldstein, K., Kaya, H., Sebag, M., Samaras, C., Malek, E., Talamo, G., Seet, C. S., Mouro, J., Pierceall, W. E., Zafar, F., Chung, W., Srinivasan, S., Agarwal, A., & Bahlis, N. J.
- Affiliations
- Hackensack University Medical Center (US)
- University of California, Los Angeles (US)
- Vancouver General Hospital (CA)
- Oncology Institute of Hope and Innovation (US)
- Washington University School of Medicine St. Louis MO USA
- Cancer Care Northwest (US)
- McGill University Health Centre Montreal QC Canada
- Cleveland Clinic (US)
- University Hospitals of Cleveland (US)
- Penn State Cancer Institute (US)
- Celgene (United States) (US)
- University of Calgary (CA)
- Corresponding author
- Siegel, David S.
- ORCID
- Venue
- British Journal of Haematology
- Publisher
- Wiley
- Published
- 2019-10-06
- Volume
- 188
- Issue
- 4
- Pages
- 501-510
- ISSN
- 0007-1048 (ISSN-L)
- 1365-2141
- PMC
- PMC7027539
- OpenAlex
- W2978510275
- Cited by
- 46
- References
- 39
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 3 · 2022: 12 · 2021: 16 · 2020: 5 · 2019: 1
- FWCI
- 6.01
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- British Journal of Haematology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc)
- Funders
- Celgene
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Keywords
- relapsed/refractory multiple myeloma, pomalidomide, low-dose dexamethasone, lenalidomide-refractory disease, treatment sequencing, overall response rate, progression-free survival, overall survival, treatment-emergent adverse events
- MeSH terms
- Lenalidomide, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Dexamethasone, Female, Humans, Male, Middle Aged, Multiple Myeloma, Thalidomide, Survival Rate, Disease-Free Survival
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