Efficacy of Lenalidomide in Myelodysplastic Syndromes
Open accessAbstract
BACKGROUND: Ineffective erythropoiesis is the hallmark of myelodysplastic syndromes. Management of the anemia caused by ineffective erythropoiesis is difficult. In patients with myelodysplastic syndromes and symptomatic anemia, we evaluated the safety and hematologic activity of lenalidomide, a novel analogue of thalidomide. METHODS: Forty-three patients with transfusion-dependent or symptomatic anemia received lenalidomide at doses of 25 or 10 mg per day or of 10 mg per day for 21 days of every 28-day cycle. All patients either had had no response to recombinant erythropoietin or had a high endogenous erythropoietin level with a low probability of benefit from such therapy. The response to treatment was assessed after 16 weeks. RESULTS: Neutropenia and thrombocytopenia, the most common adverse events, with respective frequencies of 65 percent and 74 percent, necessitated the interruption of treatment or a dose reduction in 25 patients (58 percent). Other adverse events were mild and infrequent. Twenty-four patients had a response (56 percent): 20 had sustained independence from transfusion, 1 had an increase in the hemoglobin level of more than 2 g per deciliter, and 3 had more than a 50 percent reduction in the need for transfusions. The response rate was highest among patients with a clonal interstitial deletion involving chromosome 5q31.1 (83 percent, as compared with 57 percent among those with a normal karyotype and 12 percent among those with other karyotypic abnormalities; P=0.007) and patients with lower prognostic risk. Of 20 patients with karyotypic abnormalities, 11 had at least a 50 percent reduction in abnormal cells in metaphase, including 10 (50 percent) with a complete cytogenetic remission. After a median follow-up of 81 weeks, the median duration of transfusion independence had not been reached and the median hemoglobin level was 13.2 g per deciliter (range, 11.5 to 15.8). CONCLUSIONS: Lenalidomide has hematologic activity in patients with low-risk myelodysplastic syndromes who have no response to erythropoietin or who are unlikely to benefit from conventional therapy.
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Lenalidomide has activity in del(5q) MDS by inducing degradation of CK1α, the protein product of the haploinsufficient gene CSNK1A1 located on the common deleted region of chromosome 5q, leading to activation of p53 and subsequent apoptosis.
“Lenalidomide has activity in this disease by inducing degradation of CK1α, the protein product of the haploinsufficient gene CSNK1A1 that is located on the common deleted region of chromosome 5q, leading to activation of p53 and subsequent apoptosis15,96.”
From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [96]
Del(5q) MDS HSPCs are typically sensitive to lenalidomide-mediated depletion of CK1α, which activates p53-dependent cell death.
“Del(5q) MDS HSPCs are typically sensitive to lenalidomide-mediated depletion of CK1α, which activates p53-dependent cell death15,96.”
From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [96]
Lenalidomide exerts highly favorable effects against 5q-syndrome, a type of myelodysplastic syndrome.
“it has been shown that lenalidomide exerts highly favorable effects against 5q-syndrome, a type of myelodysplastic syndrome [28,29].”
From Cereblon and its downstream substrates as molecular targets of immunomodulatory drugs (2016) · cites this paper as [29]
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- Authors
- List, A., Kurtin, S., Roe, D. J., Buresh, A., Mahadevan, D., Fuchs, D., Rimsza, L., Heaton, R., Knight, R., & Zeldis, J. B.
- Affiliations
- University of South Florida (US)
- University of Arizona (US)
- Celgene (United States) (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2005-02-10
- Volume
- 352
- Issue
- 6
- Pages
- 549-557
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2033556677
- Cited by
- 880
- References
- 30
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 15 · 2023: 19 · 2022: 24 · 2021: 26 · 2020: 27 · 2019: 12 · 2018: 40 · 2017: 28 · 2016: 21 · 2015: 43 · 2014: 31 · 2013: 41 · 2012: 48
- FWCI
- 55.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (P01CA017094, U54CA090821, 1U54CA90821-01, 5 PO1 CA17094)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- lenalidomide, myelodysplastic syndrome, anemia, ineffective erythropoiesis, transfusion independence, thalidomide analogues, karyotype abnormalities, cytogenetic remission, neutropenia, thrombocytopenia
- MeSH terms
- Lenalidomide, Adult, Aged, Aged, 80 and over, Anemia, Refractory, Bone Marrow, Female, Hematopoiesis, Humans, Male, Middle Aged, Myelodysplastic Syndromes, Neutropenia, Thalidomide, Thrombocytopenia, Gene Deletion, Angiogenesis Inhibitors
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