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Lenalidomide in Myelodysplastic Syndromes: An Erythropoiesis-Stimulating Agent or More?

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Abstract

Anemia remains the most challenging clinical manifestation to treat in patients with lower-risk myelodysplastic syndromes (MDS). Erythropoiesis-stimulating agents are widely used to treat anemia in such patients, but less than one third respond to these agents, and the duration of response is often limited. Lenalidomide, a second-generation immunomodulatory drug (IMiD), is approved by the US Food and Drug Administration for treatment of transfusion-dependent anemia in lower-risk MDS patients with deletion 5q chromosomal abnormality. Lenalidomide also has meaningful clinical activity in lower-risk patients without deletion 5q. The experience with lenalidomide in MDS is a modern example of reciprocal translational research, in which bench work led to an approved drug for patients, and clinical observations led to better understanding of the mechanism of action of the drug itself and even more understanding of the biology of the underlying disease. This article reviews the clinical experience with lenalidomide, highlighting recent understanding of the dual karyotype-dependent mechanisms of action.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Bennett JM, List AF, for the Myelodysplastic Syndromes Foundation Inc: Disparities in criteria for initiating chelation therapy for iron overload in patients with myelodysplastic syndromes (MDS) [abstract]. Blood (ASH Annual Meeting Abstracts) 2005, 106(11):Abstract 2535.

  2. Bennett JM for the MDS Foundation’s Working Group on Transfusional Iron Overload: Consensus statement on iron overload in myelodysplastic syndromes. Am J Hematol 2008;83(11):858–861.

    Google Scholar 

  3. Malcovati L, Germing U, Kuendgen A, et al.: Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol 2007;25(23):3503–3510.

    Article  PubMed  Google Scholar 

  4. Malcovati L, Della Porta MG, Cazzola M: Predicting survival and leukemic evolution in patients with myelodysplastic syndrome. Haematologica 2006;91(12):1588–1590.

    PubMed  Google Scholar 

  5. Melchert M, List AF: Management of RBC-transfusion dependence. Hematology Am Soc Hematol Educ Program 2007:398–404.

  6. Hellstrom-Lindberg E: Efficacy of erythropoietin in the myelodysplastic syndromes: a meta-analysis of 205 patients from 17 studies. Br J Haematol 1995;89(1):67–71.

    CAS  PubMed  Google Scholar 

  7. Bartlett JB, Dredge K, Dalgleish AG: The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat Rev Cancer 2004;4(4):314–322.

    Article  CAS  PubMed  Google Scholar 

  8. Komrokji R, Giagounidis A, List A: Lenalidomide therapy in MDS. In Myelodysplastic Syndromes: Pathobiology and Clinical Management, edn 2. Edited by Steensma DP. London: Informa Health Care; 2008:457–483.

    Google Scholar 

  9. Revlimid [package insert]. Summit, NJ: Celgene Corporation; 2009.

  10. List A, Kurtin S, Roe DJ, et al.: Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 2005;352(6):549–557.

    Article  CAS  PubMed  Google Scholar 

  11. List A, Dewald G, Bennett J, et al.: Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 2006;355(14):1456–1465.

    Article  CAS  PubMed  Google Scholar 

  12. •• Raza A, Reeves JA, Feldman EJ, et al.: Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood 2008;111(1):86–93. This phase 2 clinical study addresses the role of lenalidomide in treating lower-risk MDS patients without del5q.

    Article  CAS  PubMed  Google Scholar 

  13. List A, Wride K, Dewald G, et al.: Cytogenetic response to lenalidomide is associated with improved survival in patients with chromosome 5q deletion. Leuk Res 2007;31(suppl 1):s38.

    Article  Google Scholar 

  14. Germing U, Strupp C, Kuendgen A, et al. Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes. Haematologica 2006;91(12):1596–1604.

    PubMed  Google Scholar 

  15. Giagounidis A, Fenaux P, Mufti GJ, et al.: Practical recommendations on the use of lenalidomide in the management of myelodysplastic syndromes. Ann Hematol 2008;87(5):345–352.

    Article  CAS  PubMed  Google Scholar 

  16. Chen N, Lau H, Kong L, et al.: Pharmacokinetics of lenalidomide in subjects with various degrees of renal impairment and in subjects on hemodialysis. J Clin Pharmacol 2007;47(12):1466–1475.

    Article  CAS  PubMed  Google Scholar 

  17. Giagounidis AA, Germing U, Wainscoat JS, et al.: The 5q- syndrome. Hematology 2004;9(4):271–277.

    Article  CAS  PubMed  Google Scholar 

  18. Boultwood J, Pellagatti A, Cattan H, et al.: Gene expression profiling of CD34+ cells in patients with the 5q- syndrome. Br J Haematol 2007;139(4):578–589.

    Article  CAS  PubMed  Google Scholar 

  19. Liu TX, Becker MW, Jelinek J, et al.: Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation. Nat Med 2007;13(1):78–83.

    Article  PubMed  Google Scholar 

  20. Joslin JM, Fernald AA, Tennant TR, et al.: Haploinsufficiency of EGR1, a candidate gene in the del(5q), leads to the development of myeloid disorders. Blood 2007;110(2):719–726.

    Article  CAS  PubMed  Google Scholar 

  21. •• Ebert BL, Pretz J, Bosco J, et al.: Identification of RPS14 as the 5q- syndrome gene by RNA interference screen [abstract]. Blood (ASH Annual Meeting Abstracts) 2007;110(11):Abstract 1. This study demonstrates that haploinsufficiency of RPS14 recapitulates the del(5q) MDS phenotype.

  22. •• Wei S, Chen X, Rocha K, et al.: A critical role for phosphatase haplodeficiency in the selective suppression of deletion 5q MDS by lenalidomide. Proc Natl Acad Sci U S A 2009, 106(31):12974–12979. This study shed light on the possible mechanism of action and target of lenalidomide treatment.

    Article  CAS  PubMed  Google Scholar 

  23. Hoefsloot LH, Van Amelsvoort MP, Broeders LC, et al.: Erythropoietin-induced activation of STAT5 is impaired in the myelodysplastic syndrome. Blood 1997;89(5):1690–1700.

    CAS  PubMed  Google Scholar 

  24. Moutouh-De Parseval LA, Verhelle D, Glezer E, et al.: Pomalidomide and lenalidomide regulate erythropoiesis and fetal hemoglobin production in human CD34+ cells. J Clin Invest 2008;118(1):248–258.

    Article  CAS  PubMed  Google Scholar 

  25. List AF, Estes M, Williams A, et al.: Lenalidomide (CC-5013; Revlimid) promotes erythropoiesis in myelodysplastic syndromes (MDS) by CD45 protein tyrosine phosphatase (PTP) inhibition [abstract]. Blood (ASH Annual Meeting Abstracts) 2006;108(11):Abstract 1360.

  26. Ebert BL, Galili N, Tamayo P, et al.: An erythroid differentiation signature predicts response to lenalidomide in myelodysplastic syndrome. PLoS Med 2008;5(2):e35.

    Article  PubMed  Google Scholar 

  27. Burcheri S, Prebet T, Beyne-Rauzy O, et al.: Lenalidomide (LEN) in INT 2 and high risk MDS with DEL 5q. Interim results of a phase II trial by the GFM [abstract]. Blood (ASH Annual Meeting Abstracts) 2007;110(11):Abstract 820.

  28. •• Sekeres MA, Maciejewski JP, Giagounidis AN, et al.: Relationship of treatment-related cytopenias and response to lenalidomide in patients with lower-risk myelodysplastic syndromes. J Clin Oncol 2008;26(36):5943–5949. This study correlates response with development of cytopenias in del(5q) and non-del(5q) MDS patients treated with lenalidomide.

    Article  PubMed  Google Scholar 

  29. List AF, Lancet JE, Melchert M, et al.: Two-stage pharmacokinetic & efficacy study of lenalidomide alone or combined with recombinant erythropoietin (EPO) in lower risk MDS EPO-failures [PK-002] [abstract]. Blood (ASH Annual Meeting Abstracts) 2007;110(11):Abstract 4626.

  30. Sekeres MA, List AF, Cuthbertson D, et al.: Final results from a phase I combination study of lenalidomide and azacitidine in patients with higher-risk myelodysplastic syndromes (MDS) [abstract]. Blood (ASH Annual Meeting Abstracts) 2008;112(11):Abstract 221.

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Disclosure

All three authors have received research grants from Celgene Corporation and are members of the Celgene Advisory Board. Dr. Komrokji and Dr. List are also members of the Celgene Speakers Bureau.

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Authors and Affiliations

  1. H. Lee Moffitt Cancer Center and Research Institute, FOB-3rd Floor, 12902 Magnolia Drive, Tampa, FL, 33612, USA

    Rami S. Komrokji, Jeffrey E. Lancet & Alan F. List

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  1. Rami S. Komrokji
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  2. Jeffrey E. Lancet
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  3. Alan F. List
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Correspondence to Rami S. Komrokji.

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Komrokji, R.S., Lancet, J.E. & List, A.F. Lenalidomide in Myelodysplastic Syndromes: An Erythropoiesis-Stimulating Agent or More?. Curr Hematol Malig Rep 5, 9–14 (2010). https://doi.org/10.1007/s11899-009-0036-z

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  • DOI: https://doi.org/10.1007/s11899-009-0036-z

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