Medical Oncology

, Volume 27, Supplement 1, pp 43–52 | Cite as

Management of disease- and treatment-related complications in patients with multiple myeloma

  • Francesca Gay
  • Antonio PalumboEmail author
Original Paper


Treatment of myeloma has dramatically changed after introduction of novel agents, such as thalidomide, lenalidomide and bortezomib, with a significant improvement in response rate and survival of patients with myeloma. For newly diagnosed patients not eligible for transplant, the standards of care are now considered melphalan and prednisone (MP) plus thalidomide and MP plus bortezomib. Ongoing randomized trials are evaluating lenalidomide plus MP and lenalidomide plus dexamethasone. For newly diagnosed patients eligible for transplant, new induction regimens included the combination of high-dose dexamethasone plus thalidomide, high-dose dexamethasone plus lenalidomide (RD) and high-dose dexamethasone plus bortezomib (VD). The combinations RD, VD and bortezomib plus pegylated-liposomal-doxorubicin have received the US Food and Drug Administration approval for the treatment of relapsed myeloma. Different efficacious regimens are therefore now available for patients with myeloma. Disease control leads to improvement of all myeloma-related complications (anemia, bone disease, immune dysfunction and renal impairment), but physicians should take into account the choice of the therapeutic strategy, the expected toxicity profile of each of these regimens, together with the patient’s biologic age and comorbidities. Supportive care is an essential part of myeloma therapy, both for the treatment of myeloma-related complications, together with anti-myeloma treatment, and for the management of treatment-emergent adverse events. This chapter will provide an overview of frequency and management of main complications related to the disease itself and to the use of new drugs in newly diagnosed and relapsed patients with myeloma.


Myeloma Adverse events Therapy New drugs 


Conflict of interest statement

Francesca Gay declares no conflict of interest (other than the honorario reported below). Antonio Palumbo received honoraria from Celgene, Pharmion and Jansen-Cilag. The authors received an honorarium for their participation in this supplement.


  1. 1.
    Rajkumar SV, Kyle RA. Plasma Cell Disorders. In: Goldman L, Ausiello D, editors. Cecil textbook of medicine. 23rd ed. Philadelphia: W B Saunders; 2008. p. 1426–37.Google Scholar
  2. 2.
    Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;351:1860–73.CrossRefPubMedGoogle Scholar
  3. 3.
    Alexanian R, Barlogie B, Tucker S. VAD-based regimens as primary treatment for multiple myeloma. Am J Hematol. 1990;33(2):86–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Bensinger W. Stem-cell transplantation for multiple myeloma in the era of novel drugs. J Clin Oncol. 2008;26(3):480–92.CrossRefPubMedGoogle Scholar
  5. 5.
    Palumbo A, et al. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet. 2006;367:825–31.CrossRefPubMedGoogle Scholar
  6. 6.
    Facon T, 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(9594):1209–18.CrossRefPubMedGoogle Scholar
  7. 7.
    Hulin C, et al. Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial. J Clin Oncol. 2009;27(22):3664–70.CrossRefPubMedGoogle Scholar
  8. 8.
    San Miguel JF, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008;359(9):906–17.CrossRefPubMedGoogle Scholar
  9. 9.
    Zonder JA, 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. ASH Annu Meet Abstr. 2007;110(11):77.Google Scholar
  10. 10.
    Rajkumar SV, et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2010;11(1):29–37.CrossRefPubMedGoogle Scholar
  11. 11.
    Macro M, et al. Dexamethasone + Thalidomide (Dex/Thal) compared to VAD as a pre-transplant treatment in newly diagnosed multiple myeloma (MM): a randomized trial. ASH Annu Meet Abstr. 2006;108(11):57.Google Scholar
  12. 12.
    Rajkumar SV, Blood E, Vesole DH, Fonseca R, Greipp PR. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern cooperative oncology group. J Clin Oncol. 2006;24:431–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Rajkumar SV, et al. A multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone versus dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol. 2008;26:2171–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Harousseau JL, et al. VELCADE/Dexamethasone (Vel/D) Versus VAD as induction treatment prior to autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma (MM): updated results of the IFM 2005/01 Trial. ASH Annu Meet Abstr. 2007;110(11):450.Google Scholar
  15. 15.
    Spencer A, et al. Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol. 2009;26:2171–7.Google Scholar
  16. 16.
    Attal M, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006;108(10):3289–94.CrossRefPubMedGoogle Scholar
  17. 17.
    Richardson PG, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005;352(24):2487–98.CrossRefPubMedGoogle Scholar
  18. 18.
    Orlowski RZ, et al. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol. 2007;25(25):3892–901.CrossRefPubMedGoogle Scholar
  19. 19.
    Weber DM, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007;357(21):2133–42.CrossRefPubMedGoogle Scholar
  20. 20.
    Dimopoulos M, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007;357(21):2123–32.CrossRefPubMedGoogle Scholar
  21. 21.
    National Cancer Institute: Common Terminology Criteria for Adverse Events, v3.0, (CTCAE)
  22. 22.
    Palumbo A, et al. Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report From the GIMEMA Italian multiple myeloma network. J Clin Oncol. 2007;25(28):4459–65.CrossRefPubMedGoogle Scholar
  23. 23.
    Smith A, Wisloff F, Samson D. UK myeloma forum; nordic myeloma study group; British committee for standards in haematology. Guidelines on the diagnosis and management of multiple myeloma 2005. Br J Haematol. 2006;132(4):410–51.CrossRefPubMedGoogle Scholar
  24. 24.
    Mateos M-V, et al. Bortezomib (Velcade)-melphalan-prednisone (VMP) versus velcade-thalidomide-prednisone (VTP) in elderly untreated multiple myeloma patients: which is the best partner for velcade: an alkylating or an immunomodulator agent? Blood (ASH Annu Meet Abstr). 2008;112:651.Google Scholar
  25. 25.
    Palumbo A, et al. A prospective, randomized, phase III study of bortezomib, melphalan, prednisone and thalidomide (VMPT) versus bortezomib, melphalan and prednisone (VMP) in elderly newly diagnosed myeloma patients. Blood (ASH Annu Meet Abstr). 2008;112:652.Google Scholar
  26. 26.
    Reece DE, et al. Lenalidomide (Revlimid®) ± corticosteroids in elderly patients with relapsed/refractory multiple myeloma. Blood (ASH Annu Meet Abstr). 2006;108:3550.Google Scholar
  27. 27.
    Palumbo A, et al. Thalidomide for treatment of multiple myeloma: 10 years later. Blood. 2008;111(8):3968–77CrossRefPubMedGoogle Scholar
  28. 28.
    Lacy MQ, et al. Long-term results of response to therapy, time to progression, and survival with lenalidomide plus dexamethasone in newly diagnosed myeloma. Mayo Clin Proc. 2007;82(10):1179–84.CrossRefPubMedGoogle Scholar
  29. 29.
    Chanan-Khan AA, et al. Lenalidomide (L) in combination with dexamethasone (D) significantly improves time to progression (TTP) in non-stem cell transplant patients (pts) with relapsed or refractory (rel/ref) multiple myeloma (MM): analysis from MM-009 and MM-010 randomized phase III clinical trials. ASH Annu Meet Abstr. 2006;108(11):3554.Google Scholar
  30. 30.
    Hussein MA, et al. The role of vertebral augmentation in multiple myeloma: international myeloma working group consensus statement. Leukemia. 2008;22(8):1479–84.CrossRefPubMedGoogle Scholar
  31. 31.
    WHO. WHO guidelines: cancer pain relief. 2nd ed. Geneva: World Health Organisation; 1986.Google Scholar
  32. 32.
    Leigh BR, Mack CF, Matzner MB, Shimm DS. Radiation therapy for the palliation of multiple myeloma. Int J Radiat Oncol Biol Phys. 1993;25(5):801–4.PubMedGoogle Scholar
  33. 33.
    Terpos E, et al. The use of bisphosphonates in multiple myeloma: recommendations of an expert panel on behalf of the European myeloma network. Ann Oncol. 2009;20(8):1303–17.CrossRefPubMedGoogle Scholar
  34. 34.
    Silverman SL, Lendesberg R. Osteonecrosis of the jaw and the role of bisphosphonates: a critical review. Am J Med. 2009;122(2 Suppl):S33–45.CrossRefPubMedGoogle Scholar
  35. 35.
    Kastritis E, et al. Reversibility of renal failure in newly diagnosed multiple myeloma patients treated with high dose dexamethasone-containing regimens and the impact of novel agents. Haematologica. 2007;92(4):546–9.CrossRefPubMedGoogle Scholar
  36. 36.
    Bladé J, et al. Renal failure in multiple myeloma: presenting features and predictors of outcome in 94 patients from a single institution. Arch Intern Med. 1998;158(17):1889–93.CrossRefPubMedGoogle Scholar
  37. 37.
    Mezzano SA, et al. Tubular NF-kappaB and AP-1 activation in human proteinuric renal disease. Kidney Int. 2001;60(4):1366–77.CrossRefPubMedGoogle Scholar
  38. 38.
    Ltd C, inventor Revlimid® (lenalidomide) Product Information. Celgene Europe Limited. Berkshire, SL4 1NA UK. March 2009. Available from URL: 2009.
  39. 39.
    Kim SJ, et al. Bortezomib and the increased incidence of herpes zoster in patients with multiple myeloma. Clin Lymphoma Myeloma. 2008;8(4):237–40.CrossRefPubMedGoogle Scholar
  40. 40.
    Raanani P, et al. Immunoglobulin prophylaxis in chronic lymphocytic leukemia and multiple myeloma: systematic review and meta-analysis. Leuk Lymphoma. 2009;50(5):764–72.CrossRefPubMedGoogle Scholar
  41. 41.
    Bladé J. Complications of multiple myeloma. Hematol Oncol Clin North Am. 2007;21(6):1231–46.CrossRefPubMedGoogle Scholar
  42. 42.
    Richardson PG, et al. Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase III APEX trial in relapsed multiple myeloma: impact of a dose-modification guideline. Br J Haematol. 2009;144(6):890–5.CrossRefGoogle Scholar
  43. 43.
    Argyriou AA, Iconomou G, Kalofonos HP. Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature. Blood. 2008;112(5):1593–9.CrossRefPubMedGoogle Scholar
  44. 44.
    Palumbo A, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008;22(2):414–23.CrossRefPubMedGoogle Scholar
  45. 45.
    Wijermans P, et al. Melphalan + Prednisone Versus Melphalan + Prednisone + Thalidomide in induction therapy for multiple myeloma in elderly patients: final analysis of the Dutch Cooperative Group HOVON 49 Study. Blood (ASH Annu Meet Abstr). 2008;112(11):649.Google Scholar
  46. 46.
    Palumbo A, et al. A phase III study of enoxaparin vs aspirin vs low-dose warfarin as thromboprophylaxis for newly diagnosed myeloma patients treated with thalidomide based-regimens. Blood (ASH Annu Meet Abstr). 2009;114:492. Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Divisione di Ematologia dell’Università di TorinoAzienda Ospedaliera S. Giovanni Battista, Ospedale MolinetteTurinItaly

Personalised recommendations