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Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)

Health Professional Version
Last Modified: 06/24/2014

Stage Information About Plasma Cell Neoplasms

Multiple Myeloma
        International staging system
        Genetic factors and risk groups

No generally accepted staging system exists for monoclonal gammopathy of undetermined significance (MGUS), isolated plasmacytoma of bone, or extramedullary plasmacytoma. Of the plasma cell neoplasms, a staging system exists only for multiple myeloma.

Multiple Myeloma

Multiple myeloma is staged by estimating the myeloma tumor cell mass on the basis of the amount of monoclonal (or myeloma) protein (M protein) in the serum and/or urine, along with various clinical parameters, such as hemoglobin and serum calcium concentrations, the number of lytic bone lesions, and the presence or absence of renal failure. Impaired renal function worsens prognosis regardless of stage.

The stage of the disease at presentation is a strong determinant of survival, but it has little influence on the choice of therapy since almost all patients, except for rare patients with solitary bone tumors or extramedullary plasmacytomas, have generalized disease.

International staging system

The International Myeloma Working Group studied 11,171 patients, of whom 2,901 received high-dose therapy and 8,270 received only standard-dose therapy.[1]

An International Staging System was derived and is shown below in Table 2.[1]

Table 2. The International Staging System for Multiple Myeloma
Stage Criteria Median Survival (mo) 
IBeta-2-microglobulin <3.5 mg/L and albumin ≥3.5 g/dL62
IIBeta-2-microglobulin <3.5 mg/L and albumin <3.5 g/dL or beta-2-microglobulin 3.5 mg/L to <5.5 mg/L44
IIIBeta-2-microglobulin ≥5.5 mg/L29

Genetic factors and risk groups

Genetic aberrations detected by interphase fluorescence in situ hybridization (FISH) may define prognostic groups in retrospective and prospective analyses.[2,3] Short survival and shorter duration of response to therapy have been reported with t(4;14)(p16;q32), t(14; 16)(q32;q23), cytogenetic deletion of 13q-14, and deletion of 17p13 (p53 locus).[2-6] The question of whether the choice of therapy based on FISH analysis can influence outcome must await further study in prospective trials.

Newer clinical investigations are stratifying patients with multiple myeloma into so-called good-risk, intermediate-risk, and high-risk groups.[2-8] (See Table 3 below.) This stratification, based on cytogenetic findings, has been derived from retrospective analyses and requires prospective validation.[7] Bone marrow samples are sent for cytogenetic and FISH analysis. Plasma cell leukemia has a particularly poor prognosis.[9]

Table 3. Risk Groups for Multiple Myeloma
Risk Group Cytogenetic Findings Disease Characteristics Median Survival 
FISH = fluorescence in situ hybridization.
Good riskHas any of the following cytogenetic findings: (1) no adverse FISH or cytogenetics, (2) hyperdiploidy, (3) t(11;14) by FISH, or (4) t(6;14) by FISH.These patients most often have (1) disease that expresses IgG kappa monoclonal gammopathies and (2) lytic bone lesions.8–10 years
Intermediate riskt(4;14) by FISHThese patients often have IgA lambda monoclonal gammopathies and less bone disease.5 years
High riskHas any of the following cytogenetic findings: (1) del 17p by FISH, (2) t(14;16) by FISH, (3) cytogenetic del 13, (4) hypodiploidy, (5) 1q gain, or (6) plasma cell leukemia.These patients have (1) disease that expresses IgA lambda monoclonal gammopathies (often) and (2) skeletal-related complications (less often).<2 years

References
  1. Greipp PR, San Miguel J, Durie BG, et al.: International staging system for multiple myeloma. J Clin Oncol 23 (15): 3412-20, 2005.  [PUBMED Abstract]

  2. Fonseca R, Blood E, Rue M, et al.: Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood 101 (11): 4569-75, 2003.  [PUBMED Abstract]

  3. Avet-Loiseau H, Attal M, Moreau P, et al.: Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood 109 (8): 3489-95, 2007.  [PUBMED Abstract]

  4. Gertz MA, Lacy MQ, Dispenzieri A, et al.: Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32), and -17p13 in myeloma patients treated with high-dose therapy. Blood 106 (8): 2837-40, 2005.  [PUBMED Abstract]

  5. Gutiérrez NC, Castellanos MV, Martín ML, et al.: Prognostic and biological implications of genetic abnormalities in multiple myeloma undergoing autologous stem cell transplantation: t(4;14) is the most relevant adverse prognostic factor, whereas RB deletion as a unique abnormality is not associated with adverse prognosis. Leukemia 21 (1): 143-50, 2007.  [PUBMED Abstract]

  6. Sagaster V, Ludwig H, Kaufmann H, et al.: Bortezomib in relapsed multiple myeloma: response rates and duration of response are independent of a chromosome 13q-deletion. Leukemia 21 (1): 164-8, 2007.  [PUBMED Abstract]

  7. Kumar SK, Mikhael JR, Buadi FK, et al.: Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines. Mayo Clin Proc 84 (12): 1095-110, 2009.  [PUBMED Abstract]

  8. Avet-Loiseau H, Attal M, Campion L, et al.: Long-term analysis of the IFM 99 trials for myeloma: cytogenetic abnormalities [t(4;14), del(17p), 1q gains] play a major role in defining long-term survival. J Clin Oncol 30 (16): 1949-52, 2012.  [PUBMED Abstract]

  9. Ramsingh G, Mehan P, Luo J, et al.: Primary plasma cell leukemia: a Surveillance, Epidemiology, and End Results database analysis between 1973 and 2004. Cancer 115 (24): 5734-9, 2009.  [PUBMED Abstract]