A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma
Open accessAbstract
This multicenter, open-label, randomized phase 2 study evaluated 2 dose regimens of lenalidomide for relapsed, refractory myeloma. Seventy patients were randomized to receive either 30 mg once-daily or 15 mg twice-daily oral lenalidomide for 21 days of every 28-day cycle. Patients with progressive or stable disease after 2 cycles received dexamethasone. Analysis of the first 70 patients showed increased grade 3/4 myelo-suppression in patients receiving 15 mg twice daily (41% versus 13%, P = .03). An additional 32 patients received 30 mg once daily. Responses were evaluated according to European Group for Blood and Marrow Transplantation (EBMT) criteria. Overall response rate (complete, partial, or minor) to lenalidomide alone was 25% (24% for once-daily and 29% for twice-daily lenalidomide). Median overall survival in 30-mg once-daily and twice-daily groups was 28 and 27 months, respectively. Median progression-free survival was 7.7 months on once-daily versus 3.9 months on twice-daily lenalidomide (P = .2). Dexamethasone was added in 68 patients and 29% responded. Time to first occurrence of clinically significant grade 3/4 myelosuppression was shorter in the twice-daily group (1.8 vs 5.5 months, P = .05). Significant peripheral neuropathy and deep vein thrombosis each occurred in only 3%. Lenalidomide is active and well tolerated in relapsed, refractory myeloma, with the 30-mg once-daily regimen providing the basis for future studies as monotherapy and with dexamethasone.
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Lenalidomide maintenance has demonstrated a clear OS advantage (about 88% versus 80% at 3 years) with a hazard ratio for death of approximately 0.60.
“By contrast, lenalidomide has demonstrated a clear OS advantage (~88% versus 80% at 3 years) with a hazard ratio for death of approximately 0.6030,31,33,34.”
From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [33]
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- Authors
- Richardson, P. G., Blood, E., Mitsiades, C. S., Jagannath, S., Zeldenrust, S. R., Alsina, M., Schlossman, R. L., Rajkumar, S. V., Desikan, K. R., Hideshima, T., Munshi, N. C., Kelly-Colson, K., Doss, D., McKenney, M. L., Gorelik, S., Warren, D., Freeman, A., Rich, R., Wu, A., Olesnyckyj, M., Wride, K., Dalton, W. S., Zeldis, J., Knight, R., Weller, E., & Anderson, K. C.
- Affiliations
- Mayo Clinic (US)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2006-11-15
- Volume
- 108
- Issue
- 10
- Pages
- 3458-3464
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC1895441
- OpenAlex
- W2060496777
- Cited by
- 523
- References
- 35
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 3 · 2023: 7 · 2022: 14 · 2021: 14 · 2020: 10 · 2019: 8 · 2018: 13 · 2017: 19 · 2016: 19 · 2015: 13 · 2014: 21 · 2013: 26 · 2012: 42
- FWCI
- 41.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Multiple Myeloma Research Foundation
- Celgene
- National Institutes of Health (CA100707)
- National Cancer Institute (P0-1 CA78373, R01- CA50947, P50CA100707, R01CA050947)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Keywords
- lenalidomide, relapsed multiple myeloma, refractory multiple myeloma, dose comparison, myelosuppression, dexamethasone combination therapy, progression-free survival, overall response rate, drug toxicity, peripheral neuropathy, deep vein thrombosis
- MeSH terms
- Lenalidomide, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Dexamethasone, Female, Humans, Male, Middle Aged, Multiple Myeloma, Peripheral Nervous System Diseases, Recurrence, Remission Induction, Thalidomide, Survival Rate, Survival Analysis, Salvage Therapy, Venous Thrombosis
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