Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Treatment of the complications of multiple myeloma

S Vincent Rajkumar, MD
Section Editor
Robert A Kyle, MD
Deputy Editor
Rebecca F Connor, MD


Patients with multiple myeloma frequently develop complications related to their disease, including hypercalcemia, renal insufficiency, infection, and skeletal lesions, which require specific treatment in addition to therapy directed at the malignant clone [1,2]. Some of these problems are discussed in detail elsewhere within UpToDate, but will be briefly reviewed here.

The importance of these complications was highlighted in a study of death within 60 days of diagnosis in patients with myeloma entering onto the United Kingdom's Medical Research Council (MRC) trials. The incidence of early death was 10 percent, with the most common contributors being bacterial infection (50 percent) and renal failure (28 percent) [3].

Treatment of the complications of multiple myeloma will be reviewed here. The uses of chemotherapy and hematopoietic cell transplantation in the treatment of multiple myeloma are discussed separately, as is the diagnosis of multiple myeloma. (See "Overview of the management of multiple myeloma" and "Clinical features, laboratory manifestations, and diagnosis of multiple myeloma".)


Hypercalcemia is present in over 10 percent of patients with myeloma at the time of diagnosis and may require emergent treatment. Patients with hypercalcemia may be asymptomatic or complain of a variety of symptoms such as anorexia, nausea, vomiting, polyuria, polydipsia, increased constipation, weakness, confusion, or stupor. Hypercalcemia can also contribute to the development of renal insufficiency. (See "Clinical features, laboratory manifestations, and diagnosis of multiple myeloma", section on 'Hypercalcemia' and "Clinical manifestations of hypercalcemia".)

In most patients with myeloma the diagnosis of hypercalcemia does not require measurement of the ionized calcium. However, if a patient presents with an elevated serum calcium level but no associated symptoms, the ionized calcium should be measured to confirm hypercalcemia prior to the initiation of treatment since rarely the monoclonal protein binds to calcium [4]. The treatment of hypercalcemia depends upon the calcium level, the rapidity with which it developed, and the patient's symptoms. In general, the following approach may be considered:

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Aug 01, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med 2004; 351:1860.
  2. Smith A, Wisloff F, Samson D, et al. Guidelines on the diagnosis and management of multiple myeloma 2005. Br J Haematol 2006; 132:410.
  3. Augustson BM, Begum G, Dunn JA, et al. Early mortality after diagnosis of multiple myeloma: analysis of patients entered onto the United kingdom Medical Research Council trials between 1980 and 2002--Medical Research Council Adult Leukaemia Working Party. J Clin Oncol 2005; 23:9219.
  4. Annesley TM, Burritt MF, Kyle RA. Artifactual hypercalcemia in multiple myeloma. Mayo Clin Proc 1982; 57:572.
  5. Burnette BL, Leung N, Rajkumar SV. Renal improvement in myeloma with bortezomib plus plasma exchange. N Engl J Med 2011; 364:2365.
  6. 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.
  7. Blimark C, Holmberg E, Mellqvist UH, et al. Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients. Haematologica 2015; 100:107.
  8. Rapezzi D, Sticchi L, Racchi O, et al. Influenza vaccine in chronic lymphoproliferative disorders and multiple myeloma. Eur J Haematol 2003; 70:225.
  9. Robertson JD, Nagesh K, Jowitt SN, et al. Immunogenicity of vaccination against influenza, Streptococcus pneumoniae and Haemophilus influenzae type B in patients with multiple myeloma. Br J Cancer 2000; 82:1261.
  10. Ljungman P, Nahi H, Linde A. Vaccination of patients with haematological malignancies with one or two doses of influenza vaccine: a randomised study. Br J Haematol 2005; 130:96.
  11. Oken MM, Pomeroy C, Weisdorf D, Bennett JM. Prophylactic antibiotics for the prevention of early infection in multiple myeloma. Am J Med 1996; 100:624.
  12. Talamo G, Angtuaco E, Walker RC, et al. Avascular necrosis of femoral and/or humeral heads in multiple myeloma: results of a prospective study of patients treated with dexamethasone-based regimens and high-dose chemotherapy. J Clin Oncol 2005; 23:5217.
  13. Henry DH, Costa L, Goldwasser F, et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol 2011; 29:1125.
  14. Stopeck AT, Lipton A, Body JJ, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol 2010; 28:5132.
  15. Hussein MA, Vrionis FD, Allison R, et al. The role of vertebral augmentation in multiple myeloma: International Myeloma Working Group Consensus Statement. Leukemia 2008; 22:1479.
  16. McDonald RJ, Gray LA, Cloft HJ, et al. The effect of operator variability and experience in vertebroplasty outcomes. Radiology 2009; 253:478.
  17. Dudeney S, Lieberman IH, Reinhardt MK, Hussein M. Kyphoplasty in the treatment of osteolytic vertebral compression fractures as a result of multiple myeloma. J Clin Oncol 2002; 20:2382.
  18. Fourney DR, Schomer DF, Nader R, et al. Percutaneous vertebroplasty and kyphoplasty for painful vertebral body fractures in cancer patients. J Neurosurg 2003; 98:21.
  19. Lane JM, Hong R, Koob J, et al. Kyphoplasty enhances function and structural alignment in multiple myeloma. Clin Orthop Relat Res 2004; :49.
  20. Hentschel SJ, Burton AW, Fourney DR, et al. Percutaneous vertebroplasty and kyphoplasty performed at a cancer center: refuting proposed contraindications. J Neurosurg Spine 2005; 2:436.
  21. Berenson J, Pflugmacher R, Jarzem P, et al. Balloon kyphoplasty versus non-surgical fracture management for treatment of painful vertebral body compression fractures in patients with cancer: a multicentre, randomised controlled trial. Lancet Oncol 2011; 12:225.
  22. Buchbinder R, Osborne RH, Ebeling PR, et al. A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. N Engl J Med 2009; 361:557.
  23. Kallmes DF, Comstock BA, Heagerty PJ, et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med 2009; 361:569.
  24. Featherstone C, Delaney G, Jacob S, Barton M. Estimating the optimal utilization rates of radiotherapy for hematologic malignancies from a review of the evidence: part II-leukemia and myeloma. Cancer 2005; 103:393.
  25. Lecouvet F, Richard F, Vande Berg B, et al. Long-term effects of localized spinal radiation therapy on vertebral fractures and focal lesions appearance in patients with multiple myeloma. Br J Haematol 1997; 96:743.
  26. Terpos E, Morgan G, Dimopoulos MA, et al. International Myeloma Working Group recommendations for the treatment of multiple myeloma-related bone disease. J Clin Oncol 2013; 31:2347.
  27. Leigh BR, Kurtts TA, Mack CF, et al. Radiation therapy for the palliation of multiple myeloma. Int J Radiat Oncol Biol Phys 1993; 25:801.
  28. Rades D, Hoskin PJ, Stalpers LJ, et al. Short-course radiotherapy is not optimal for spinal cord compression due to myeloma. Int J Radiat Oncol Biol Phys 2006; 64:1452.
  29. Anaissie EJ, Coleman EA, Goodwin JA, et al. Prophylactic recombinant erythropoietin therapy and thalidomide are predictors of venous thromboembolism in patients with multiple myeloma: limited effectiveness of thromboprophylaxis. Cancer 2012; 118:549.
  30. Palumbo A, Rajkumar SV, San Miguel JF, et al. International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation. J Clin Oncol 2014; 32:587.
  31. Garton JP, Gertz MA, Witzig TE, et al. Epoetin alfa for the treatment of the anemia of multiple myeloma. A prospective, randomized, placebo-controlled, double-blind trial. Arch Intern Med 1995; 155:2069.
  32. Osterborg A, Boogaerts MA, Cimino R, et al. Recombinant human erythropoietin in transfusion-dependent anemic patients with multiple myeloma and non-Hodgkin's lymphoma--a randomized multicenter study. The European Study Group of Erythropoietin (Epoetin Beta) Treatment in Multiple Myeloma and Non-Hodgkin's Lymphoma. Blood 1996; 87:2675.
  33. Dammacco F, Castoldi G, Rödjer S. Efficacy of epoetin alfa in the treatment of anaemia of multiple myeloma. Br J Haematol 2001; 113:172.
  34. Gertz MA, Kyle RA. Hyperviscosity syndrome. J Intensive Care Med 1995; 10:128.
  35. Kristinsson SY, Fears TR, Gridley G, et al. Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma. Blood 2008; 112:3582.
  36. Kristinsson SY, Pfeiffer RM, Björkholm M, et al. Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma: a population-based study. Blood 2010; 115:4991.
  37. Libourel EJ, Sonneveld P, van der Holt B, et al. High incidence of arterial thrombosis in young patients treated for multiple myeloma: results of a prospective cohort study. Blood 2010; 116:22.
  38. Richardson PG, Delforge M, Beksac M, et al. Management of treatment-emergent peripheral neuropathy in multiple myeloma. Leukemia 2012; 26:595.