Advertisement

Current Hematologic Malignancy Reports

, Volume 11, Issue 2, pp 111–117 | Cite as

Diagnostic Advances in Multiple Myeloma

  • Kevin Barley
  • Ajai ChariEmail author
Multiple Myeloma (P Kapoor, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Multiple Myeloma

Abstract

There have been several advances in the diagnosis of multiple myeloma (MM) in recent years. Serum free light chains have improved the ability to diagnose light chain MM; however, there are still difficulties in the serologic diagnosis of MM in some cases, particularly IgA MM. A novel heavy/light chain assay is able to improve the accuracy of diagnosis in these cases. Free light chains may also improve the diagnosis of extramedullary disease in difficult cases such as disease involving the central nervous system, pleura, or ascites. Advances in imaging such as whole body low-dose computed tomography (CT) whole body magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) have improved sensitivity in identifying lytic bone lesions, which would enable earlier treatment, and monitoring of osseous disease particularly in non- or oligosecretory disease. New techniques such as fused PET/MRI may further enhance the diagnosis of both bone lesions and extramedullary disease.

Keywords

Multiple myeloma Diagnosis HevyLite Free light chains Extramedullary disease Whole body low-dose CT 

Notes

Compliance with Ethical Standards

Conflict of Interest

Kevin Barley and Ajai Chari each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Rajkumar SV, Larson D, Kyle RA. Diagnosis of smoldering multiple myeloma. N Engl J Med. 2011;365(5):474–5. doi: 10.1056/NEJMc1106428.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Larsen JT, Kumar SK, Dispenzieri A, Kyle RA, Katzmann JA, Rajkumar SV. Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma. Leukemia. 2013;27(4):941–6. doi: 10.1038/leu.2012.296.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Kastritis E, Moulopoulos LA, Terpos E, Koutoulidis V, Dimopoulos MA. The prognostic importance of the presence of more than one focal lesion in spine MRI of patients with asymptomatic (smoldering) multiple myeloma. Leukemia. 2014;28(12):2402–3. doi: 10.1038/leu.2014.230.CrossRefPubMedGoogle Scholar
  4. 4.
    Dispenzieri A, Kyle R, Merlini G, et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia. 2009;23(2):215–24. doi: 10.1038/leu.2008.307.CrossRefPubMedGoogle Scholar
  5. 5.
    Kaplan JS, Horowitz GL. Twenty-four-hour Bence-Jones protein determinations: can we ensure accuracy? Arch Pathol Lab Med. 2011;135(8):1048–51. doi: 10.5858/2010-0547-oar.CrossRefPubMedGoogle Scholar
  6. 6.
    Katzmann JA, Dispenzieri A, Kyle RA, et al. Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays. Mayo Clin Proc. 2006;81(12):1575–8. doi: 10.4065/81.12.1575.CrossRefPubMedGoogle Scholar
  7. 7.
    Shah NN, Nooka AK, Harvey D, et al. Using serum free light chain (SFLC) ratio and serum protein electrophoresis (SPEP) as a substitute for 24-hour urine studies in myeloma patients. Blood. 2013;122(21):2.Google Scholar
  8. 8.
    Wozney JL, Damluji AA, Ahmed F, Zangari M, Loughran Jr TP, Talamo G. Estimation of daily proteinuria in patients with multiple myeloma by using the protein-to-creatinine ratio in random urine samples. Acta Haematol. 2010;123(4):226–9. doi: 10.1159/000313448.CrossRefPubMedGoogle Scholar
  9. 9.
    Le Bricon T, Bengoufa D, Benlakehal M, Bousquet B, Erlich D. Urinary free light chain analysis by the Freelite immunoassay: a preliminary study in multiple myeloma. Clin Biochem. 2002;35(7):565–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Keren DFHR. Clinical Indications and Applications of Serum and Urine Protein Electrophoresis. In: Folds ECHJ, Dietrich R, editors. Manual of Clinical Immunology. 7th ed. Washington, D.C.: American Society for Microbiology Press; 2006. p. 75–87.Google Scholar
  11. 11.
    Bradwell AR, Harding SJ, Fourrier NJ, et al. Assessment of monoclonal gammopathies by nephelometric measurement of individual immunoglobulin kappa/lambda ratios. Clin Chem. 2009;55(9):1646–55. doi: 10.1373/clinchem.2009.123828.CrossRefPubMedGoogle Scholar
  12. 12.
    Wolff F, Debaugnies F, Rozen L, et al. Assessment of the diagnostic performances of IgA heavy and light chain pairs in patients with IgA monoclonal gammopathy. Clin Biochem. 2013;46(1–2):79–84. doi: 10.1016/j.clinbiochem.2012.09.023.CrossRefPubMedGoogle Scholar
  13. 13.
    Boyle EM, Fouquet G, Guidez S, et al. IgA kappa/IgA lambda heavy/light chain assessment in the management of patients with IgA myeloma. Cancer. 2014;120(24):3952–7. doi: 10.1002/cncr.28946.CrossRefPubMedGoogle Scholar
  14. 14.•
    Ludwig H, Milosavljevic D, Zojer N, et al. Immunoglobulin heavy/light chain ratios improve paraprotein detection and monitoring, identify residual disease and correlate with survival in multiple myeloma patients. Leukemia. 2013;27(1):213–9. doi: 10.1038/leu.2012.197. The diagnostic performance of HevyLite was evaluated using prospectively collected sera from newly diagnosed MM patients. HevyLite was able to quantify M proteins that were unquantifiable with conventional tests and more sensitive than SPEP.
  15. 15.
    Lokhorst HM, Plesner T, Laubach JP, et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med. 2015;373(13):1207–19. doi: 10.1056/NEJMoa1506348.CrossRefPubMedGoogle Scholar
  16. 16.
    Lonial S, Dimopoulos M, Palumbo A, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373(7):621–31. doi: 10.1056/NEJMoa1505654.CrossRefPubMedGoogle Scholar
  17. 17.
    Axel AE, McCudden CR, Xie H, Hall BM, Sasser AK. Development of clinical assay to mitigate daratumumab, an IgG1 kappa monoclonal antibody, interference with serum immunofixation (IFE) and clinical assessment of M-protein response in multiple myeloma. Cancer Res. 2014;74(19):1. doi: 10.1158/1538-7445.am2014-2563.Google Scholar
  18. 18.
    Grisold A, Weber C, Hainfellner J, et al. MRI negative meningeal myeloma with abducens nerve palsies responding to intrathecal chemotherapy. J Neurol Sci. 2014;347(1–2):359–60. doi: 10.1016/j.jns.2014.10.005.CrossRefPubMedGoogle Scholar
  19. 19.
    Chen CI, Masih-Khan E, Jiang H, et al. Central nervous system involvement with multiple myeloma: long term survival can be achieved with radiation, intrathecal chemotherapy, and immunomodulatory agents. Br J Haematol. 2013;162(4):483–8. doi: 10.1111/bjh.12414.CrossRefPubMedGoogle Scholar
  20. 20.
    Marron TU, Ramanathan L, Chari A. Diagnostic utility of measuring free light chains in the cerebrospinal fluid of patients with multiple myeloma. Clin Lymphoma Myeloma Leuk. 2015;15(6):e127–31. doi: 10.1016/j.clml.2015.02.028.CrossRefPubMedGoogle Scholar
  21. 21.
    Presslauer S, Milosavljevic D, Brucke T, Bayer P, Hubl W. Elevated levels of kappa free light chains in CSF support the diagnosis of multiple sclerosis. J Neurol. 2008;255(10):1508–14. doi: 10.1007/s00415-008-0954-z.CrossRefPubMedGoogle Scholar
  22. 22.
    Kamble R, Wilson CS, Fassas A, et al. Malignant pleural effusion of multiple myeloma: prognostic factors and outcome. Leuk Lymphoma. 2005;46(8):1137–42. doi: 10.1080/10428190500102845.CrossRefPubMedGoogle Scholar
  23. 23.
    Palmer HE, Wilson CS, Bardales RH. Cytology and flow cytometry of malignant effusions of multiple myeloma. Diagn Cytopathol. 2000;22(3):147–51.CrossRefPubMedGoogle Scholar
  24. 24.
    Hilal N, Atallah A. Ascites as the presenting symptom of multiple myeloma in a scleroderma patient. Case Rep Rheumatol. 2014;2014:235958. doi: 10.1155/2014/235958.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Tsukamoto A, Yoshiki Y, Yamazaki S, Kumano K, Nakamura F, Kurokawa M. The significance of free light chain measurements in the diagnosis of myelomatous pleural effusion. Ann Hematol. 2014;93(3):507–8. doi: 10.1007/s00277-013-1818-x.CrossRefPubMedGoogle Scholar
  26. 26.
    Muccio VE, Saraci E, Gilestro M, et al. Multiple myeloma: New surface antigens for the characterization of plasma cells in the era of novel agents. Cytometry B Clin Cytom. 2016;90(1):81–90. doi: 10.1002/cyto.b.21279.CrossRefPubMedGoogle Scholar
  27. 27.
    Horger M, Claussen CD, Bross-Bach U, et al. Whole-body low-dose multidetector row-CT in the diagnosis of multiple myeloma: an alternative to conventional radiography. Eur J Radiol. 2005;54(2):289–97. doi: 10.1016/j.ejrad.2004.04.015.CrossRefPubMedGoogle Scholar
  28. 28.•
    Regelink JC, Minnema MC, Terpos E, et al. Comparison of modern and conventional imaging techniques in establishing multiple myeloma-related bone disease: a systematic review. Br J Haematol. 2013;162(1):50–61. doi: 10.1111/bjh.12346. This systematic review analyzes all studies comparing conventional and modern imaging techniques in the diagnosis of MM.
  29. 29.
    Gleeson TG, Moriarty J, Shortt CP, et al. Accuracy of whole-body low-dose multidetector CT (WBLDCT) versus skeletal survey in the detection of myelomatous lesions, and correlation of disease distribution with whole-body MRI (WBMRI). Skelet Radiol. 2009;38(3):225–36. doi: 10.1007/s00256-008-0607-4.CrossRefGoogle Scholar
  30. 30.
    Spira D, Weisel K, Brodoefel H, Schulze M, Kaufmann S, Horger M. Can whole-body low-dose multidetector CT exclude the presence of myeloma bone disease in patients with monoclonal gammopathy of undetermined significance (MGUS)? Acad Radiol. 2012;19(1):89–94. doi: 10.1016/j.acra.2011.09.016.CrossRefPubMedGoogle Scholar
  31. 31.
    Kropil P, Fenk R, Fritz LB, et al. Comparison of whole-body 64-slice multidetector computed tomography and conventional radiography in staging of multiple myeloma. Eur Radiol. 2008;18(1):51–8. doi: 10.1007/s00330-007-0738-3.CrossRefPubMedGoogle Scholar
  32. 32.
    Nanni C, Zamagni E, Farsad M, et al. Role of 18F-FDG PET/CT in the assessment of bone involvement in newly diagnosed multiple myeloma: preliminary results. Eur J Nucl Med Mol Imaging. 2006;33(5):525–31. doi: 10.1007/s00259-005-0004-3.CrossRefPubMedGoogle Scholar
  33. 33.
    Schirrmeister H, Buck AK, Bergmann L, Reske SN, Bommer M. Positron emission tomography (PET) for staging of solitary plasmacytoma. Cancer Biother Radiopharm. 2003;18(5):841–5. doi: 10.1089/108497803770418382.CrossRefPubMedGoogle Scholar
  34. 34.
    Bredella MA, Steinbach L, Caputo G, Segall G, Hawkins R. Value of FDG PET in the assessment of patients with multiple myeloma. AJR Am J Roentgenol. 2005;184(4):1199–204. doi: 10.2214/ajr.184.4.01841199.CrossRefPubMedGoogle Scholar
  35. 35.
    Bauerle T, Hillengass J, Fechtner K, et al. Multiple myeloma and monoclonal gammopathy of undetermined significance: importance of whole-body versus spinal MR imaging. Radiology. 2009;252(2):477–85. doi: 10.1148/radiol.2522081756.CrossRefPubMedGoogle Scholar
  36. 36.
    Dinter DJ, Neff WK, Klaus J, et al. Comparison of whole-body MR imaging and conventional X-ray examination in patients with multiple myeloma and implications for therapy. Ann Hematol. 2009;88(5):457–64. doi: 10.1007/s00277-008-0621-6.CrossRefPubMedGoogle Scholar
  37. 37.•
    Giles SL, deSouza NM, Collins DJ, et al. Assessing myeloma bone disease with whole-body diffusion-weighted imaging: comparison with x-ray skeletal survey by region and relationship with laboratory estimates of disease burden. Clin Radiol. 2015;70(6):614–21. doi: 10.1016/j.crad.2015.02.013. A prospective comparison of WBMRI and skeletal survey simultaneously evaluated in patients with MM found that WBMRI had an excellent interobserver reliability and detected more lesions than skeletal survey.
  38. 38.
    Narquin S, Ingrand P, Azais I, et al. Comparison of whole-body diffusion MRI and conventional radiological assessment in the staging of myeloma. Diagn Interv Imaging. 2013;94(6):629–36. doi: 10.1016/j.diii.2013.01.005.CrossRefPubMedGoogle Scholar
  39. 39.
    Moulopoulos LA, Gika D, Anagnostopoulos A, et al. Prognostic significance of magnetic resonance imaging of bone marrow in previously untreated patients with multiple myeloma. Ann Oncol : Off J Eur Soc Med Oncol / ESMO. 2005;16(11):1824–8. doi: 10.1093/annonc/mdi362.CrossRefGoogle Scholar
  40. 40.
    Baur-Melnyk A, Buhmann S, Becker C, et al. Whole-body MRI versus whole-body MDCT for staging of multiple myeloma. AJR Am J Roentgenol. 2008;190(4):1097–104. doi: 10.2214/ajr.07.2635.CrossRefPubMedGoogle Scholar
  41. 41.
    Cascini GL, Falcone C, Console D, et al. Whole-body MRI and PET/CT in multiple myeloma patients during staging and after treatment: personal experience in a longitudinal study. Radiol Med. 2013;118(6):930–48. doi: 10.1007/s11547-013-0946-7.CrossRefPubMedGoogle Scholar
  42. 42.
    Schwenzer NF, Pfannenberg AC. PET/CT, MR, and PET/MR in lymphoma and melanoma. Semin Nucl Med. 2015;45(4):322–31. doi: 10.1053/j.semnuclmed.2015.03.006.CrossRefPubMedGoogle Scholar
  43. 43.
    Heacock L, Weissbrot J, Raad R, et al. PET/MRI for the evaluation of patients with lymphoma: initial observations. AJR Am J Roentgenol. 2015;204(4):842–8. doi: 10.2214/ajr.14.13181.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538–48. doi: 10.1016/s1470-2045(14)70442-5.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Multiple Myeloma ProgramIcahn School of Medicine at Mount SinaiNew YorkUSA

Personalised recommendations