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Lenalidomide for Initial Therapy of Newly Diagnosed Multiple Myeloma

  • Shaji Kumar
Part of the Contemporary Hematology book series (CH)

Introduction

Multiple myeloma (MM) is the second most common hematologic malignancy after non-Hodgkin'slymphoma, and over 19,000 individuals were estimated to be diagnosed with this disease in 2007, with nearly 12,000 myeloma-related deaths during this time period.1 It is characterized by accumulation of clonal plasma cells in the bone marrow that secrete a monoclonal protein in the majority and usually presents with destructive bone lesions, anemia, hyper-calcemia, and/or renal insufficiency.2 Conventional therapy with alkylating agents and steroids or other chemotherapy combinations result in a median survival of 3–4 years, which is prolonged by nearly a year with high-dose therapy and stem cell rescue.2, 3, 4Myeloma is believed to be incurable with the current approaches, but several new promising therapies have been introduced in the past few years that have vastly improved the treatment options for these patients. These include the immunomodulatory derivatives of tha-lidomide...

Keywords

Multiple Myeloma Stem Cell Transplant Myeloma Cell Area Under Curve Very Good Partial Response 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, et al. Cancer statistics, 2005. CA Cancer J Clin 2005;55(1):10–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med 2004;351(18):1860–73.PubMedCrossRefGoogle Scholar
  3. 3.
    Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003;78(1):21–33.PubMedCrossRefGoogle Scholar
  4. 4.
    Kumar SK, Therneau TM, Gertz MA, Lacy MQ, Dispenzieri A, Rajkumar SV,. Clinical course of patients with relapsed multiple myeloma. Mayo Clin Proc 2004;79(7):867–74.PubMedCrossRefGoogle Scholar
  5. 5.
    Rogerson G. Thalidomide and congenital abnormalities. Lancet 1962;1:691.Google Scholar
  6. 6.
    Grabstad H, Golbey R. Clinical experience with thalidomide in patients with cancer. Clin Pharmacol Ther 1965;6:298–302.Google Scholar
  7. 7.
    Olson KB, Hall TC, Horton J, Khung CL, Hosley HF. Thalidomide (N-phthaloylglutamimide) in the treatment of advanced cancer. Clin Pharmacol Ther 1965;6(3):292–297.PubMedGoogle Scholar
  8. 8.
    D'Amato RJ, Loughnan MS, Flynn E, Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 1994;91(9):4082–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Kenyon BM, Browne F, D'Amato RJ. Effects of thalidomide and related metabolites in a mouse corneal model of neovascularization. Exp Eye Res 1997;64(6):971–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285(21):1182–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Folkman J. Seminars in Medicine of the Beth Israel Hospital, Boston. Clinical applications of research on angiogenesis. N Engl J Med 1995;333(26):1757–63.PubMedCrossRefGoogle Scholar
  12. 12.
    Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999;341(21):1565–71.PubMedCrossRefGoogle Scholar
  13. 13.
    Rajkumar SV. Thalidomide: tragic past and promising future. Mayo Clin Proc 2004;79(7):899–903.PubMedCrossRefGoogle Scholar
  14. 14.
    Richardson PG, Schlossman RL, Weller E, Hideshima T, Mitsiades C, Davies F,. Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood 2002;100(9):3063–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Schey SA, Fields P, Bartlett JB, Clarke IA, Ashan G, Knight RD,. Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma. J Clin Oncol 2004;22(16):3269–76.PubMedCrossRefGoogle Scholar
  16. 16.
    Bartlett JB, Dredge K, Dalgleish AG. The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat Rev Cancer 2004;4(4):314–22.PubMedCrossRefGoogle Scholar
  17. 17.
    Hideshima T, Chauhan D, Shima Y, Raje N, Davies FE, Tai YT,. Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood 2000;96(9):2943–50.PubMedGoogle Scholar
  18. 18.
    Davies FE, Raje N, Hideshima T, Lentzsch S, Young G, Tai Y-T,. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 2001;98(1):210–216.PubMedCrossRefGoogle Scholar
  19. 19.
    Mitsiades N, Mitsiades CS, Poulaki V, Chauhan D, Richardson PG, Hideshima T, et al. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 2002;99(12):4525–30.PubMedCrossRefGoogle Scholar
  20. 20.
    Fujita J, Mestre JR, Zeldis JB, Subbaramaiah K, Dannenberg AJ. Thalidomide and its analogues inhibit lipopolysaccharide-mediated induction of cyclooxygenase-2. Clin Cancer Res 2001;7(11):3349–55.PubMedGoogle Scholar
  21. 21.
    Payvandi F W u L H aley M Schafer PH, Zhang LH, Chen RS, et al. Immunomodulatory drugs inhibit expression of cyclooxygenase-2 from TNF-alpha, IL-1beta, and LPS-stimulated human PBMC in a partially IL-10-dependent manner. Cell Immunol 2004;230(2):81–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Davies FE, Raje N, Hideshima T, Lentzsch S, Young G, Tai YT, et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 2001;98(1):210–6.PubMedCrossRefGoogle Scholar
  23. 23.
    LeBlanc R, Hideshima T, Catley LP, Shringarpure R, Burger R, Mitsiades N, et al. Immunomodulatory drug costimulates T cells via the B7-CD28 pathway. Blood 2004;103(5):1787–90.PubMedCrossRefGoogle Scholar
  24. 24.
    Gupta D, Treon SP, Shima Y, Hideshima T, Podar K, Tai YT,. et al Adherence of multiple myeloma cells to bone marrow stromal cells upregulates vascular endothelial growth factor secretion: therapeutic applications. Leukemia 2001;15(12):1950–61.PubMedGoogle Scholar
  25. 25.
    Dredge K, Horsfall R, Robinson SP, Zhang LH, Lu L, Tang Y, et al. Orally administered lenalidomide (CC-5013) is anti-angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro. Microvasc Res 2005;69(1–2):56–63.PubMedCrossRefGoogle Scholar
  26. 26.
    Lentzsch S, LeBlanc R, Podar K, Davies F, Lin B, Hideshima T, et al. Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo. Leukemia 2003;17(1):41–4.PubMedCrossRefGoogle Scholar
  27. 27.
    Dimopoulos MA, Weber D, Chen C, Spencer A, Niesvizky R, Attal M, et al. Evaluating oral lenalidomide (Revlimid-) and dexamethasone versus placebo and dexamethasone in patients with relapsed or refractory multiple myeloma. Haematologica 2005;90(S2):160.Google Scholar
  28. 28.
    Lacy M, Gertz M, Dispenzieri A, Hayman S, Geyer S, Zeldenrust S,. Lenalidomide plus dexamethasone (Rev/Dex) in newly diagnosed myeloma: response to therapy, time to progression, and survival. ASH Annual Meeting Abstracts 2006;108(11):798.Google Scholar
  29. 29.
    Rajkumar SV, Jacobus S, Callander N, Fonseca R, Vesole D, Williams M, et al. Phase III trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4A03): a trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol (Meeting Abstracts) 2007;25(18_suppl):LBA8025-.Google Scholar
  30. 30.
    Niesvizky R, Jayabalan DS, Furst JR, Cho HJ, Pearse RN, Zafar F, et al. Clarithromycin, lenalidomide and dexamethasone combination therapy as primary treatment of multiple myeloma. J Clin Oncol (Meeting Abstracts) 2006;24(18_suppl):7545-.Google Scholar
  31. 31.
    Palumbo A, Bringhen S, Caravita T, Merla E, Capparella V, Callea V, et al. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melpha-lan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet 2006;367(9513):825–31.PubMedCrossRefGoogle Scholar
  32. 32.
    Facon T, Mary J, Harousseau J, Huguet F, Berthou C, Grosbois B, et al. Superiority of melphalan-prednisone (MP) + thalidomide (THAL) over MP and autologous stem cell transplantation in the treatment of newly diagnosed elderly patients with multiple myeloma. J Clin Oncol (Meeting Abstracts) 2006;24(18_suppl):1-.Google Scholar
  33. 33.
    Palumbo A, Falco P, Benevolo G, Canepa L, D'Ardia S, Gozzetti A, et al. Oral lenalidomide plus melphalan and prednisone (R-MP) for newly diagnosed multiple myeloma. J Clin Oncol (Meeting Abstracts) 2006;24(18_suppl):7518-.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Shaji Kumar
    • 1
  1. 1.Mayo ClinicRochesterUSA

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