Skip to main content
SpringerLink
Log in

Spotlight on Lenalidomide in Relapsed or Refractory Multiple Myeloma

  • Adis Spotlight
  • Published:
BioDrugs Aims and scope Submit manuscript

Abstract

In several countries, including the US and in Europe, oral lenalidomide in combination with oral dexamethasone is approved for the treatment of multiple myeloma patients (aged ≥18 years) who have received at least one prior antimyeloma therapy. The key therapeutic mechanisms of action of lenalidomide (a thalidomide analog) reside in its immunomodulatory, antiproliferative, and anti-angiogenic properties. In patients with multiple myeloma, lenalidomide has dual effects, exerting a direct antitumor response by inhibiting proliferation and by inducing apoptosis of tumor cells. Lenalidomide also acts to enhance the immune system by inducing the activation of immune effector cells, such as T cells and natural killer cells, and inducing cytokine production.

In the pivotal MM-009 and MM-010 phase III registration trials, treatment with lenalidomide plus dexamethasone was effective and had a manageable safety and tolerability profile in relapsed or refractory patients with multiple myeloma. In robust pharmacoeconomic analyses based on these trials, relative to dexamethasone, lenalidomide plus dexamethasone treatment met the assumed willingness-to-pay threshold for cost effectiveness from the UK and Scottish healthcare payer perspective in this patient population. The UK National Institute for Health and Clinical Excellence and the Scottish Medicines Consortium considered that the health economic case for lenalidomide plus dexamethasone treatment was demonstrated for patients who had received at least two prior antimyeloma therapies. In addition, in pharmacoeconomic analyses based on indirect comparisons of clinical efficacy, regulatory agencies in Norway and Sweden considered that lenalidomide plus dexamethasone treatment was cost effective relative to bortezomib in patients who have received at least one prior antimyeloma therapy. Furthermore, compared with placebo plus dexamethasone, treatment with lenalidomide plus dexamethasone significantly prolonged the median time to progression, increased overall response rates and prolonged overall survival, with significantly longer median time to progression and overall response rates observed for all subgroups of patients. Thus, combination therapy with lenalidomide plus dexamethasone provides a valuable option for the treatment of relapsed or refractory adult patients with multiple myeloma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Davies F, Baz R. Lenalidomide mode of action: linking bench and clinical findings. Blood Rev 2010; 24Suppl. 1: S13–9

    Article  PubMed  Google Scholar 

  2. Chanan-Khan AA, Cheson BD. Lenalidomide for the treatment of B-cell malignancies. J Clin Oncol 2008; 26 (9): 1544–52

    Article  PubMed  CAS  Google Scholar 

  3. Reske T, Fulciniti M, Munshi NC. Mechanism of action of immunomodulatory agents in multiple myeloma. Med Oncol 2010; 27Suppl. 1: 7–13

    Article  Google Scholar 

  4. Li S, Gill N, Lentzsch S. Recent advances of IMiDs in cancer therapy. Curr Opin Oncol 2010; 22: 579–85

    Article  PubMed  Google Scholar 

  5. Kotla V, Goel S, Nischal S, et al. Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol 2009; 2: 36

    Article  PubMed  Google Scholar 

  6. Teo SK. Properties of thalidomide and its analogues: implications for anti-cancer therapy. AAPS J 2005; 7 (1): E14–9

    Article  PubMed  CAS  Google Scholar 

  7. Breitkreutz I, Raab MS, Vallet S, et al. Lenalidomide inhibits osteoclasto-genesis, survival factors and bone-remodeling markers in multiple myeloma. Leukemia 2008; 22 (10): 1925–32

    Article  PubMed  CAS  Google Scholar 

  8. 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

    Article  PubMed  CAS  Google Scholar 

  9. Burington B, Barlogie B, Zhan F, et al. Tumor cell gene expression changes following short-term in vivo exposure to single agent chemotherapeutics are related to survival in multiple myeloma. Clin Cancer Res 2008; 14 (15): 4821–9

    Article  PubMed  CAS  Google Scholar 

  10. Gandhi AK, Kang J, Capone L, et al. Dexamethasone synergizes with lenalidomide to inhibit multiple myeloma tumor growth, but reduces lenalidomide-induced immunomodulation of T and NK cell function. Curr Cancer Drug Targets 2010; 10 (2): 155–67

    Article  PubMed  CAS  Google Scholar 

  11. Heider U, Fleissner C, Zavrski I, et al. Bone markers in multiple myeloma. Eur J Cancer 2006; 42: 1544–53

    Article  PubMed  CAS  Google Scholar 

  12. Dimopoulos M, Terpos E, Comenzo RL, et al. International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of multiple myeloma. Leukemia 2009; 23 (9): 1545–56

    Article  PubMed  CAS  Google Scholar 

  13. European Medicines Agency. Summary of product characteristics: Revlimid® [online]. Available from URL: http://www.ema.europa.eu/docs/en-GB/doument_library/EPAR_-_Product_Information/human/000717/WC500056018.pdf [Accessed 2010 Sep 13]

  14. Celgene Corporation. Revlimid® (lenalidomide) 5mg, 10mg, 15mg and 25 mg capsules: US prescribing information [online]. Available from URL: http://www.revlimid.com/pdf/REVLIMID_PI.pdf [Accessed 2010 Aug 9]

  15. Iida S, Chou T, Okamoto S, et al. Lenalidomide plus dexamethasone treatment in Japanese patients with relapsed/refractory multiple myeloma [published erratum appears in Int J Hematol 2010; 92 (1): 127-8]. Int J Hematol 2010; 92 (1): 118–26

    Article  PubMed  CAS  Google Scholar 

  16. 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

    Article  PubMed  CAS  Google Scholar 

  17. 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): 1466–75

    Article  PubMed  CAS  Google Scholar 

  18. Weber DM, Chen C, Niesvizky R, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 2007; 357 (21): 2133–42

    Article  PubMed  CAS  Google Scholar 

  19. Dimopoulos M, Spencer A, Attal M, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 2007; 357 (21): 2123–32

    Article  PubMed  CAS  Google Scholar 

  20. Wang M, Dimopoulos MA, Chen C, et al. Lenalidomide plus dexamethasone is more effective than dexamethasone alone in patients with relapsed or refractory multiple myeloma regardless of prior thalidomide exposure. Blood 2008; 112 (12): 4445–51

    Article  PubMed  CAS  Google Scholar 

  21. Dimopoulos MA, Chen C, Spencer A, et al. Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia 2009; 23 (11): 2147–52

    Article  PubMed  CAS  Google Scholar 

  22. Dimopoulos MA, Kastritis E, Rosinol L, et al. Pathogenesis and treatment of renal failure in multiple myeloma. Leukemia 2008; 22 (8): 1485–93

    Article  PubMed  CAS  Google Scholar 

  23. Dimopoulos M, Alegre A, Stadtmauer EA, et al. The efficacy and safety of lenalidomide plus dexamethasone in relapsed and/or refractory multiple myeloma patients with impaired renal function. Cancer 2010; 116 (16): 3807–14

    Article  PubMed  CAS  Google Scholar 

  24. Chen C, Reece DE, Siegel D, et al. Expanded safety experience with lenalidomide plus dexamethasone in relapsed or refractory multiple myeloma. Br J Haematol 2009; 146 (2): 164–70

    Article  PubMed  CAS  Google Scholar 

  25. Ishak J, Dimopoulos MA, Weber D, et al. Declining rates of adverse events and dose modifications with lenalidomide in combination with dexamethasone [abstract no. 3708]. Blood 2008; 112 (11)

  26. Delforge M, Blau IW, Hernandez MT, et al. Post-Approval Safety Study (PASS) of lenalidomide compared with other treatments in patients with relapsed or refractory multiple myeloma: evaluation of peripheral neuropathy in the first 1011 patients [abstract no. 1939]. Blood 2010; 116 (21)

  27. Deniz B, Morgan G, Schey S, et al. Economic evaluation of lenalidomide combined with dexamethasone for the treatment of multiple myeloma in the UK [abstract no. 2400]. Blood 2008; 112 (11)

  28. Deniz HB, Ishak KJ, Edwards DR, et al. Economic evaluation of lenalidomide for the treatment of multiple myeloma in Wales in patients who have received at least one prior therapy [abstract no. 0804]. Haematologica 2008; 93Suppl. 1: 320–1

    Google Scholar 

  29. Deniz B, Ishak KJ, Shearer A, et al. Economic evaluation of lenalidomide use for multiple myeloma in Scotland in patients who have received one prior therapy [abstract no. PSY14]. Value Health 2008; 11 (3): A156

    Article  Google Scholar 

  30. National Institute for Health and Clinical Excellence. Lenalidomide for the treatment of multiple myeloma in people who have received at least one prior therapy: NICE technology appraisal guidance 171 [online]. Available from URL: http://www.nice.org.uk/nicemedia/pdf/TA171GuidanceWord.doc [Accessed 2010 Sep 30]

  31. Scottish Medicines Consortium. Resubmission: lenalidomide 5mg, 10mg, 15mg and 25 mg capsules (Revlimid®): no. (441/08) [online]. Available from URL: http://www.scottishmedicines.org.uk/files/lenalidomide_Revlimid_FINAL_April_2010_Resubmission_Amended_160610.pdf [Accessed 2011 Mar1]

  32. Statens legemiddelverk. Reimbursement report lenalidomide (Revlimid) to treatment of multiple myeloma: assessment of the application for preapproved reimbursement [online]. Available from URL: http://www.legemiddelverket.no/upload/Refusjonsrapport_Revlimid.pdf [Accessed 2011 Mar 8]

  33. Tandvårdsoch Läkemedelsförmånsverket. Dental and Pharmaceutical Benefits Agency, TLV decides that the following drugs should be included in the reimbursement from 2010-06-30 to the table specified prices. TLV determines the alternative price to the same amount of AIP [online]. Available from URL: http://www.tlv.se/Upload/Beslut_2010/bes100701-revlimid.pdf [Accessed 2011 Mar 2]

  34. Scott LJ, Lyseng-Williamson KA. Lenalidomide: a review of its use in the treatment of relapsed or refractory multiple myeloma. Drugs 2011; 71 (5): 625–49

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments and Disclosures

The full-text article[34] from which this spotlight was derived was reviewed by: S. Iida, Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; A. Palumbo, Myeloma Unit, Division of Haematology, University of Turin, Turin, Italy; N. Uaprasert, Division of Haematology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; M. Wang, Department of Lymphoma and Myeloma, MD Anderson Cancer Center, Houston, Texas, USA; M. Zangari, Division of Hematology, Blood/Bone Marrow Transplant and Myeloma, University of Utah, Salt Lake City, Utah, USA; L. Zhang, Department of Lymphoma and Myeloma, MD Anderson Cancer Center, Houston, Texas, USA.

The manufacturer of the agent under review was offered an opportunity to comment on the original article during the peer review process. Changes resulting from comments received were made by the authors on the basis of scientific merit. The preparation of the original article and this spotlight was not supported by any external funding.

Author information

Authors and Affiliations

  1. Adis, a Wolters Kluwer Business, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, Auckland, 0754, New Zealand

    Lesley J. Scott & Katherine A. Lyseng-Williamson

Authors
  1. Lesley J. Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katherine A. Lyseng-Williamson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lesley J. Scott.

Additional information

Adapted and reproduced from the original article published in Drugs 2011; 71 (5): 625–649

Rights and permissions

Reprints and permissions

About this article

Cite this article

Scott, L.J., Lyseng-Williamson, K.A. Spotlight on Lenalidomide in Relapsed or Refractory Multiple Myeloma. BioDrugs 25, 333–337 (2011). https://doi.org/10.2165/11207120-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11207120-000000000-00000

Keywords

Search

Navigation