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Myeloma

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

Abstract

We present a pooled update of two large, multicenter MM-009 and MM-010 placebo-controlled randomized phase III trials that included 704 patients and assessed lenalidomide plus dexamethasone versus dexamethasone plus placebo in patients with relapsed/refractory multiple myeloma (MM). Patients in both studies were randomized to receive 25 mg daily oral lenalidomide or identical placebo, plus 40 mg oral dexamethasone. In this pooled analysis, using data up to unblinding (June 2005 for MM-009 and August 2005 for MM-010), treatment with lenalidomide plus dexamethasone significantly improved overall response (60.6 vs 21.9%, P<0.001), complete response rate (15.0 vs 2.0%, P<0.001), time to progression (median of 13.4 vs 4.6 months, P<0.001) and duration of response (median of 15.8 months vs 7 months, P<0.001) compared with dexamethasone-placebo. At a median follow-up of 48 months for surviving patients, using data up to July 2008, a significant benefit in overall survival (median of 38.0 vs 31.6 months, P=0.045) was retained despite 47.6% of patients who were randomized to dexamethasone-placebo receiving lenalidomide-based treatment after disease progression or study unblinding. Low β2-microglobulin and low bone marrow plasmacytosis were associated with longer survival. In conclusion, these data confirm the significant response and survival benefit with lenalidomide and dexamethasone.

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References

  1. Piazza FA, Gurrieri C, Trentin L, Semenzato G . Towards a new age in the treatment of multiple myeloma. Ann Hematol 2007; 86: 159–172.

    Article  Google Scholar 

  2. 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: 21–33.

    Article  Google Scholar 

  3. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T et al. Cancer statistics, 2008. CA Cancer J Clin 2008; 58: 71–96.

    Article  Google Scholar 

  4. Facon T, Mary JY, Hulin C, Benboubker L, Attal M, Pegourie B et al. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet 2007; 370: 1209–1218.

    CAS  Article  Google Scholar 

  5. Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005; 352: 2487–2498.

    CAS  Article  Google Scholar 

  6. Dimopoulos MA, Spencer A, Attal M, Prince HM, Harousseau JC, Dmoszynska A et al. Multiple Myeloma (010) study investigators. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 2007; 357: 2123–2132.

    CAS  Article  Google Scholar 

  7. Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA et al. Multiple Myeloma (009) study investigators. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 2007; 357: 2133–2142.

    CAS  Article  Google Scholar 

  8. Kumar SK, Rajkumar V, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008; 111: 2516–2520.

    CAS  Article  Google Scholar 

  9. Richardson PG, Mitsiades C, Hideshima T, Anderson KC . Lenalidomide in multiple myeloma. Expert Rev Anticancer Ther 2006; 6: 1165–1173.

    CAS  Article  Google Scholar 

  10. Kastritis E, Dimopoulos MA . The evolving role of lenalidomide in the treatment of hematologic malignancies. Expert Opin Pharmacother 2007; 8: 497–509.

    CAS  Article  Google Scholar 

  11. Thomas SK, Richards TA, Weber DM . Lenalidomide in multiple myeloma. Best Pract Res Clin Haematol 2007; 20: 717–735.

    CAS  Article  Google Scholar 

  12. Richardson PG, Schlossman RL, Weller E, Hideshima T, Mitsiades C, Davies F et al. Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood 2002; 100: 3063–3067.

    CAS  Article  Google Scholar 

  13. Richardson PG, Blood E, Mitsiades CS, Jagannath S, Zeldenrust SR, Alsina M et al. A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood 2006; 108: 3458–3464.

    CAS  Article  Google Scholar 

  14. Bladé J, Samson D, Reece D, Apperley J, Björkstrand B, Gahrton G et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol 1998; 102: 1115–1123.

    Article  Google Scholar 

  15. Stadtmauer EA, Weber DM, Niesvizky R, Belch A, Prince PH, San Miguel JF et al. Lenalidomide in combination with dexamethasone at first relapse in comparison with its use as later salvage therapy in relapsed or refractory multiple myeloma. Eur J Haematol 2009; 82: 426–432.

    CAS  Article  Google Scholar 

  16. San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M et al. Bortezomib plus melphalan and prednisone for initial treatment for multiple myeloma. N Engl J Med 2008; 359: 906–917.

    CAS  Article  Google Scholar 

  17. 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 2007; 25, Abstract LBA8025.

  18. Zonder JA, Crowley J, Hussein MA, Bolejack V, Moore DF, Whittenberger BF et al. Superiority of Lenalidomide (Len) Plus High-Dose Dexamethasone (HD) Compared to HD Alone as Treatment of Newly-Diagnosed Multiple Myeloma (NDMM): results of the randomized, double-blinded, placebo-controlled SWOG Trial S0232. Blood 2007; 110, Abstract 77.

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Acknowledgements

We received editorial support in the preparation of this article, funded by Celgene. We, however, were fully responsible for content and editorial decisions for this article.

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Dimopoulos, M., 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 23, 2147–2152 (2009). https://doi.org/10.1038/leu.2009.147

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Keywords

  • multiple myeloma
  • lenalidomide
  • dexamethasone
  • myelosuppression

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