International Journal of Hematology

, Volume 96, Issue 2, pp 254–262 | Cite as

Lenalidomide in combination with dexamethasone improves survival and time-to-progression in patients ≥65 years old with relapsed or refractory multiple myeloma

  • Asher A. Chanan-Khan
  • Sagar Lonial
  • Donna Weber
  • Ivan Borrello
  • Robin Foà
  • Andrzej Hellmann
  • Meletios Dimopoulos
  • Arlene S. Swern
  • Robert Knight
Original Article

Abstract

Two pivotal, phase III, randomised, placebo-controlled, registration trials (MM-009 and MM-010) showed that lenalidomide plus dexamethasone was more effective than placebo plus dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma. This pooled, retrospective subanalysis of MM-009 and MM-010 analysed outcomes according to patient age. A total of 704 patients (390 aged <65 years, 232 aged 65–74 years, and 82 aged ≥75 years) received lenalidomide or placebo, both in combination with dexamethasone. The overall response rate (ORR) was significantly higher in patients treated with lenalidomide plus dexamethasone versus placebo plus dexamethasone in all age groups (P < 0.0001 for all). Median progression-free survival (PFS) and median time-to-progression (TTP) were similar, and both were significantly longer with lenalidomide plus dexamethasone in all age groups (P < 0.001 for all). Median overall survival (OS) favoured lenalidomide plus dexamethasone in all age groups, although the difference was not statistically significant. Adverse events of anaemia, febrile neutropenia, deep-vein thrombosis, neuropathy, and gastrointestinal disorders increased with age. Lenalidomide combined with dexamethasone improved the ORR and prolonged PFS, TTP, and OS compared with placebo plus dexamethasone, irrespective of age. This finding was consistent with the overall MM-009 and MM-010 populations.

Keywords

Lenalidomide Elderly Multiple myeloma Relapsed Refractory 

Notes

Acknowledgments

The authors received editorial support from Excerpta Medica in the preparation of this manuscript, funded by Celgene Corporation.

Conflict of interst

A.A.C-K. and M.A.D. have received consulting and lecture fees from Celgene. S.L. and A.H. have received consulting fees from Celgene. D.W. has received grant support and lecture fees from Celgene. I.B. has received grant support and consulting and lecture fees from Celgene. A.S.S. and R.K. are employees of Celgene. R.F. has no disclosures.

References

  1. 1.
    Mileshkin L, Prince HM. The adverse prognostic impact of advanced age in multiple myeloma. Leuk Lymphoma. 2005;46:951–66.PubMedCrossRefGoogle Scholar
  2. 2.
    National Cancer Institute. Surveillance, Epidemiology and End Results (SEER). Fast Stats. http://seer.cancer.gov/faststats (accessed 18 July 2011).
  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;78:21–33.PubMedCrossRefGoogle Scholar
  4. 4.
    Rodon P, Linassier C, Gauvain JB, Benboubker L, Goupille P, Maigre M, et al. Multiple myeloma in elderly patients: presenting features and outcome. Eur J Haematol. 2001;66:11–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Palumbo A, Avonto I, Bringhen S, Falcone A, Liberati M, Boccadoro M. Hematologic cancer in the elderly: new and existing therapeutic strategies. http://www.asco.org/ASCOv2/Home/Education%20&%20Training/Educational%20Book/PDF%20Files/2007/07geriatric02.pdf (accessed 18 July 2011).
  6. 6.
    Cavallo F, Ambrosini MT, Rus C, Boccadoro M, Palumbo A. The treatment of the elderly multiple myeloma patients. Leuk Lymphoma. 2007;48:469–80.PubMedCrossRefGoogle Scholar
  7. 7.
    Suppiah R, Srkalovic JG, Hussein MA. Immunomodulatory analogues of thalidomide in the treatment of multiple myeloma. Clin Lymphoma Myeloma. 2006;6:301–5.PubMedCrossRefGoogle Scholar
  8. 8.
    Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007;357:2123–32.PubMedCrossRefGoogle Scholar
  9. 9.
    Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007;357:2133–42.PubMedCrossRefGoogle Scholar
  10. 10.
    Dimopoulos MA, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer EA, 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;23:2147–52.PubMedCrossRefGoogle Scholar
  11. 11.
    Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20:1467–73.PubMedCrossRefGoogle Scholar
  12. 12.
    National Cancer Institute. Cancer Therapy Evaluation Program. Common Terminology Criteria for Adverse Events (CTCAE) and Common Toxicity Criteria (CTC). Common Toxicity Criteria (CTC) v2.0, published April 30, 1999. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_20 (accessed 18 July 2011).
  13. 13.
    Wang M, Dimopoulos MA, Chen C, Cibeira MT, Attal M, Spencer A, 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;112:4445–51.PubMedCrossRefGoogle Scholar
  14. 14.
    Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, et al. Safety and efficacy of bortezomib in high-risk and elderly patients with relapsed multiple myeloma. Br J Haematol. 2007;137:429–35.PubMedCrossRefGoogle Scholar
  15. 15.
    Gay F, Rajkumar SV, Falco P, Kumar S, Dispenzieri A, Petrucci MT, et al. Lenalidomide plus dexamethasone vs. lenalidomide plus melphalan and prednisone: a retrospective study in newly diagnosed elderly myeloma. Eur J Haematol. 2010;85:200–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Nucci M, Anaissie E. Infections in patients with multiple myeloma in the era of high-dose therapy and novel agents. Clin Infect Dis. 2009;49:1211–25.PubMedCrossRefGoogle Scholar
  17. 17.
    Dimopoulos MA, Hussein M, Swern AS, Weber D. Impact of lenalidomide dose on progression-free survival in patients with relapsed or refractory multiple myeloma. Leukemia. 2011;25:1620–6.PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2012

Authors and Affiliations

  • Asher A. Chanan-Khan
    • 1
  • Sagar Lonial
    • 2
  • Donna Weber
    • 3
  • Ivan Borrello
    • 4
  • Robin Foà
    • 5
  • Andrzej Hellmann
    • 6
  • Meletios Dimopoulos
    • 7
  • Arlene S. Swern
    • 8
  • Robert Knight
    • 8
  1. 1.Department of MedicineRoswell Park Cancer Institute BuffaloBuffaloUSA
  2. 2.Emory Winship Cancer InstituteAtlantaUSA
  3. 3.M.D. Anderson Cancer CenterHoustonUSA
  4. 4.The Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimoreUSA
  5. 5.Department of Cellular Biotechnologies and HematologySapienza University of RomeRomeItaly
  6. 6.Department of Hematology and TransplantologyMedical University of GdańskGdańskPoland
  7. 7.The University of Athens School of MedicineAthensGreece
  8. 8.Celgene CorporationSummitNJUSA

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