Lenalidomide in Relapsed or Refractory Multiple Myeloma

  • Sheeba K. Thomas
  • Tiffany A. Richards
  • Donna M. Weber
Part of the Contemporary Hematology book series (CH)


Until the late-1990s, combinations of alkylating agents, steroids, and anthracyclines formed the basis of therapy for patients with multiple myeloma (MM), with regimens such as melphalan—prednisone, high-dose dexamethasone, and VAD (vincristine, Adriamycin®, dexamethasone) providing partial response (PR) rates of up to 55% and complete response (CR) rates of up to 10% in previously untreated patients.1, 2, 3 Among patients with either primary refractory or relapsing myeloma, only 25–40% achieved PR with these regimens, and rates of CR were negligible.4,5 The introduction of thalidomide in 1999 began a new era of agents effective for the treatment of MM, with single-agent response rates of 28–36% in relapsing/refractory patients.6, 7, 8, 9 When given together with dexamethasone, response rates approximated 47–55% in this population.7,10, 11, 12More recently, lenal-idomide, an analogue of thalidomide, has emerged, and is associated with single-agent response rates of...


Vascular Endothelial Growth Factor Multiple Myeloma Maximum Tolerate Dose Myeloma Cell Partial Response Rate 
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  1. 1.
    Alexanian R, Barlogie B, Tucker S, et al. VAD-based regimens as primary treatment for multiple myeloma. American Journal of Hematology. 1990;33(2):86–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Alexanian R, Bergsagel DE, Migliore PJ, et al. Melphalan therapy for plasma cell myeloma. Blood. 1968;31(1):1–10.PubMedGoogle Scholar
  3. 3.
    Alexanian R, Dimopoulos MA, Delasalle K, et al. Primary dexamethasone treatment of multiple myeloma. Blood. 1992;80(4):887–90.PubMedGoogle Scholar
  4. 4.
    Alexanian R, Barlogie B, Dixon D, et al. High-dose glucocorticoid treatment of resistant myeloma. Annals of Internal Medicine. 1986;105(1):8–11.PubMedGoogle Scholar
  5. 5.
    Barlogie B, Smith L, Alexanian R. Effective treatment of advanced multiple myeloma refractory to alkylating agents. The New England Journal of Medicine. 1984;310(21):1353–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. New Engl J Med. 1999; 341 (21): 1565–71.PubMedCrossRefGoogle Scholar
  7. 7.
    Alexanian R, Weber D, Anagnostopoulos A, et al. Thalidomide with or with out dexamethasone for refractory or relapsing multiple myeloma. Seminars in Hematology. 2003;40(4 Suppl 4):3–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Glasmacher A, Hahn C, Hoffmann F, et al. A systematic review of phase-II trials of thalidomide monotherapy in patients with relapsed or refractory multiple myeloma. British Journal of Haematology. 2006;132(5):584–93.PubMedCrossRefGoogle Scholar
  9. 9.
    Barlogie B, Desikan R, Eddlemon P, et al. Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: Identification of prognostic factors in a phase 2 study of 169 patients. Blood. 2001;98(2):492–4.PubMedCrossRefGoogle Scholar
  10. 10.
    Dimopoulos MA, Anagnostopoulos A, Weber D. Treatment of plasma cell dyscrasias with thalidomide and its derivatives. Journal of Clinical Oncology. 2003;21(23):4444–54.PubMedCrossRefGoogle Scholar
  11. 11.
    Dimopoulos MA, Zervas K, Kouvatseas G, et al. Thalidomide and dexam-ethasone combination for refractory multiple myeloma. Annals of Oncology. 2001;12(7):991–5.PubMedCrossRefGoogle Scholar
  12. 12.
    Weber DM, Gavino M, Delasalle K, et al. Thalidomide alone or with dexametha-sone for multiple myeloma. Blood. 1999;94(604a).Google Scholar
  13. 13.
    Richardson PG, Blood E, Mitsiades CS, et al. A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood. 2006;108(10):3458–64.PubMedCrossRefGoogle Scholar
  14. 14.
    Richardson PG, Schlossman RL, Weller E, et al. 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.
    Zangari M, Tricot G, Zeldis J, et al. Results of a phase I study of CC-5013 for the treatment of multiple myeloma (MM) patients who relapse after high dose chemotherapy (HDCT). Blood. 2001:98(775a).Google Scholar
  16. 16.
    Weber DM, Chen C, Niesvizky R, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. New England Journal of Medicine. 2007;357:2133–2142.PubMedCrossRefGoogle Scholar
  17. 17.
    Dimopoulos MA, Spencer A, Attal M, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. New England Journal of Medicine. 2007; 357:2123–2132.PubMedCrossRefGoogle Scholar
  18. 18.
    Wang M, Knight R, Dimopoulos M, et al. Lenalidomide in combination with dex-amethasone was more effective than dexamethasone in patients who have received prior thalidomide for relapsed or refractory multiple myeloma. ASH Annual Meeting Abstracts. 2006;108(11):3553.Google Scholar
  19. 19.
    Anderson KC. Lenalidomide and thalidomide: Mechanisms of action—similarities and differences. Seminars in Hematology. 2005;42(4 Suppl 4):S3–8.PubMedCrossRefGoogle Scholar
  20. 20.
    De Raeve H, Vanderkerken K. Immunomodulatory drugs as a therapy for multiple myeloma. Current Pharmaceutical Biotechnology. 2006;7:415–21.PubMedCrossRefGoogle Scholar
  21. 21.
    Gupta D, Treon SP, Shima Y, 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
  22. 22.
    Hideshima T, Chauhan D, Shima Y, et al. Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood. 2000;96(9):2943–50.PubMedGoogle Scholar
  23. 23.
    Mitsiades N, Mitsiades CS, Poulaki V, et al. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood. 2002;99(12):4525–30.PubMedCrossRefGoogle Scholar
  24. 24.
    Davies FE, Raje N, Hideshima T, et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood. 2001;98(1):210–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Chang DH, Liu N, Klimek V, et al. Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: Therapeutic implications. Blood. 2006;108(2):618–21.PubMedCrossRefGoogle Scholar
  26. 26.
    Dredge K, Marriott JB, MacDonald CD, et al. Novel thalidomide analgues display anti-angiogenic activity independently of immunomodulatory effects. British Journal of Cancer. 2002;87(10):1166–72.PubMedCrossRefGoogle Scholar
  27. 27.
    Kumar S, Rajkumar SV. Thalidomide and lenalidomide in the treatment of multiple myeloma. European Journal of Cancer. 2006;42(11):1612–22.PubMedCrossRefGoogle Scholar
  28. 28.
    Weber D, Wang M, Chen C, et al. Lenalidomide plus high-dose dexamethasone provides improved overall survival compared to high-dose dexamethasone alone for relapsed or refractory multiple myeloma (MM): Results of 2 phase III studies (MM-009, MM-010) and subgroup analysis of patients with impaired renal function. ASH Annual Meeting Abstracts. 2006;108(11):3547.Google Scholar
  29. 29.
    Reece DE, Masih-Khan E, Chen C, et al. Use of lenalidomide (Revlimid®) + /−Corticosteroids in relapsed/refractory multiple myeloma patients with elevated baseline serum creatinine levels. Blood (ASH Annual Meeting Abstracts). 2006;108:3548.Google Scholar
  30. 30.
    Kastritis E, Dimopoulos MA. The evolving role of lenalidomide in the treatment of hematologic malignancies. Expert Opinion on Pharmacotherapy. 2007;8(4):497–509.PubMedCrossRefGoogle Scholar
  31. 31.
    Reece DE, Masih-Khan E, Chen C, et al. Lenalidomide (Revlimid®) + /− Corticosteroids in elderly patients with relapsed/refractory multiple myeloma. Blood (ASH Annual Meeting Abstracts). 2006;108:3550.Google Scholar
  32. 32.
    Knight R. Lenalidomide and venous thrombosis in multiple myeloma. The New England Journal of Medicine. 2006;354(19):2079.PubMedCrossRefGoogle Scholar
  33. 33.
    Zonder JA, Durie BGM, McCoy J, Crowley J, Zeldis JB, Ghannam, et al. High incidence of thrombotic events observed in patients receiving lenalidomide (L) + Dexamethasone (D) (LD) as first-line therapy for multiple myeloma (MM) without aspirin (ASA) prophylaxis. ASH Annual Meeting Abstracts. 2005;106(11):3455.Google Scholar
  34. 34.
    Zonder JA, Barlogie B, Durie BGM, et al. Thrombotic complications in patients with newly diagnosed multiple myeloma treated with lenalidomide and dexamethasone: Benefit of aspirin prophylaxis. Blood. 2006;108(1):403–4.PubMedCrossRefGoogle Scholar
  35. 35.
    Rajkumar SV, Hayman SR, Lacy MQ, et al. Combination therapy with lenal-idomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma [see comment]. Blood. 2005;106(13):4050–3.PubMedCrossRefGoogle Scholar
  36. 36.
    Palumbo A, Falco P, Falcone A, et al. Oral Revlimid(R) plus melphalan and prednisone (R-MP) for newly diagnosed multiple myeloma: Results of a multicenter phase I/II study. ASH Annual Meeting Abstracts. 2006;108(11):800.Google Scholar
  37. 37.
    Palumbo A, Rajkumar SV, Dimopoulos MA, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008;22(2):414–23.PubMedCrossRefGoogle Scholar
  38. 38.
    Zeldis JB, Williams BA, Thomas SD, et al. S.T.E.P.S.: A comprehensive program for controlling and monitoring access to thalidomide. Clinical Therapeutics. 1999;21(2):319–30.PubMedCrossRefGoogle Scholar
  39. 39.
    Sviggum HP, Davis MDP, Rajkumar SV, et al. Dermatologic adverse effects of lena-lidomide therapy for amyloidosis and multiple myeloma. Archives of Dermatology. 2006;142(10):1298–302.PubMedCrossRefGoogle Scholar
  40. 40.
    Zangari M, Barlogie B, Jacobson J, et al. Revlimid 25 mg (REV 25) × 20 versus 50 mg (REV 50) × 10 q 28 days with bridging of 5 mg × 10 versus 10 mg × 5 as post-transplant salvage therapy for multiple myeloma (MM). Blood. 2003.102(11):1642.Google Scholar
  41. 41.
    Richardson P, Jagannath S, Hussein M, et al. A multicenter, single-arm, open-label study to evaluate the efficacy and safety of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma: Preliminary results. ASH Annual Meeting Abstracts. 2005;106(11):1565.Google Scholar
  42. 42.
    Chanan-Khan AA, Weber D, Dimopoulos M, et al. Lenalidomide (L) in combination with dexamethasone (D) improves survival and time to progression in elderly patients (pts) with relapsed or refractory (rel/ref) multiple myeloma (MM). Blood (ASH Annual Meeting Abstracts). 2006;108:3551.Google Scholar
  43. 43.
    Bahlis NJ, Mansoor A, Lategan JC, et al. Lenalidomide overcomes poor prognosis conferred by deletion of chromosome 13 and t(4;14) in multiple myeloma: MM016 trial. Blood (ASH Annual Meeting Abstracts). 2006;108:3557.Google Scholar
  44. 44.
    Garcia-Sanz R, Gonzalez-Porras JR, Hernandez JM, et al. The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma. Leukemia. 2004;18(4):856–63.PubMedCrossRefGoogle Scholar
  45. 45.
    Morgan GJ, Schey SA, Wu P, Srikanth M, et al. Lenalidomide (Revlimid), in combination with cyclophosphamide and dexamethasone (RCD), is an effective and tolerated regimen for myeloma patients. British Journal of Haematology. 2007;137(3):268–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Morgan GJ, Schey S, Wu P, et al. Lenolidamide (Revlimid), in combination with cyclophosphamide and dexamethasone (CRD) is an effective regimen for heavily pre-treated myeloma patients. ASH Annual Meeting Abstracts. 2006;108(11):3555.Google Scholar
  47. 47.
    Knop S, Gerecke C, Topp MS, et al. Lenalidomide (Revlimid™), Adriamycin and dexamethasone chemotherapy (RAD) is safe and effective in treatment of relapsed multiple myeloma—First results of a German multicenter phase I/II trial. Blood (ASH Annual Meeting Abstracts). 2006;108(11):408.Google Scholar
  48. 48.
    Baz R, Walker E, Karam MA, et al. Lenalidomide and pegylated liposomal doxorubicin-based chemotherapy for relapsed or refractory multiple myeloma: safety and efficacy. Annals of Oncology. 2006;17(12):1766—71.PubMedCrossRefGoogle Scholar
  49. 49.
    Breitkreutz I, Tai Y, Li X, Coffey R, et al. Lenalidomide and bortezomib induce osteoclast cytotoxicity and decrease BAFF secretion in osteoclasts in human multiple myeloma: Clinical implications. Journal of Clinical Oncology. 2006;24(18S):7606.Google Scholar
  50. 50.
    Richardson P, Schlossman R, Munshi N, et al. A phase 1 trial of lenalidomide (REVLIMID(R)) with bortezomib (VELCADE(R)) in relapsed and refractory multiple myeloma. ASH Annual Meeting Abstracts. 2005;106(11):365.Google Scholar
  51. 51.
    Richardson PG, Jagannath S, Avigan DE, et al. Lenalidomide plus bortezomib (Rev-Vel) in relapsed and/or refractory multiple myeloma (MM): Final results of a multicenter phase 1 trial. ASH Annual Meeting Abstracts. 2006;108(11):405.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Sheeba K. Thomas
    • 1
  • Tiffany A. Richards
    • 1
  • Donna M. Weber
  1. 1.Anderson Cancer CenterHoustonUSA

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