Abstract
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.
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References
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.
Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;351:1860–73.
Alexanian R, Barlogie B, Tucker S. VAD-based regimens as primary treatment for multiple myeloma. Am J Hematol. 1990;33(2):86–9.
Bensinger W. Stem-cell transplantation for multiple myeloma in the era of novel drugs. J Clin Oncol. 2008;26(3):480–92.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Attal M, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006;108(10):3289–94.
Richardson PG, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005;352(24):2487–98.
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.
Weber DM, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007;357(21):2133–42.
Dimopoulos M, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007;357(21):2123–32.
National Cancer Institute: Common Terminology Criteria for Adverse Events, v3.0, (CTCAE) http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_v3.0.
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.
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.
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.
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.
Reece DE, et al. Lenalidomide (Revlimid®) ± corticosteroids in elderly patients with relapsed/refractory multiple myeloma. Blood (ASH Annu Meet Abstr). 2006;108:3550.
Palumbo A, et al. Thalidomide for treatment of multiple myeloma: 10 years later. Blood. 2008;111(8):3968–77
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.
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.
Hussein MA, et al. The role of vertebral augmentation in multiple myeloma: international myeloma working group consensus statement. Leukemia. 2008;22(8):1479–84.
WHO. WHO guidelines: cancer pain relief. 2nd ed. Geneva: World Health Organisation; 1986.
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.
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.
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.
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.
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.
Mezzano SA, et al. Tubular NF-kappaB and AP-1 activation in human proteinuric renal disease. Kidney Int. 2001;60(4):1366–77.
Ltd C, inventor Revlimid® (lenalidomide) Product Information. Celgene Europe Limited. Berkshire, SL4 1NA UK. March 2009. Available from URL: http://emc.medicines.org.uk/printfriendlydocument.aspx?documentid=19841&companyid=1868 2009.
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.
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.
Bladé J. Complications of multiple myeloma. Hematol Oncol Clin North Am. 2007;21(6):1231–46.
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.
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.
Palumbo A, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008;22(2):414–23.
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.
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.
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.
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Gay, F., Palumbo, A. Management of disease- and treatment-related complications in patients with multiple myeloma. Med Oncol 27 (Suppl 1), 43–52 (2010). https://doi.org/10.1007/s12032-010-9542-z
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DOI: https://doi.org/10.1007/s12032-010-9542-z