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Cancer Health Center

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Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®): Treatment - Health Professional Information [NCI] - General Information About Plasma Cell Neoplasms

There are several types of plasma cell neoplasms. These diseases are all associated with a monoclonal (or myeloma) protein (M protein). They include monoclonal gammopathy of undetermined significance (MGUS), isolated plasmacytoma of the bone, extramedullary plasmacytoma, and multiple myeloma.

(Refer to the Lymphoplasmacytic Lymphoma (Waldenström Macroglobulinemia) section in the PDQ summary on Adult Non-Hodgkin Lymphoma Treatment for more information.)

Incidence and Mortality

Estimated new cases and deaths from multiple myeloma in the United States in 2014:[1]

  • New cases: 24,050.
  • Deaths: 11,090.

Clinical Presentation and Evaluation

Table 1. Clinical Presentation of Plasma Cell Neoplasms

Plasma Cell Neoplasm M Protein Type Pathology Clinical Presentation
MGUS = monoclonal gammopathy of undetermined significance.
MGUS IgG kappa or lambda; or IgA kappa or lambda <10% plasma cells in bone marrow Asymptomatic, with minimal evidence of disease (aside from the presence of an M protein)[2]
Isolated plasmacytoma of bone IgG kappa or lambda; or IgA kappa or gamma Solitary lesion of bone; <10% plasma cells in marrow of uninvolved site Asymptomatic or symptomatic
Extramedullary plasmacytoma IgG kappa or lambda; or IgA kappa or gamma Solitary lesion of soft tissue; most commonly occurs in the nasopharynx, tonsils, or paranasal sinuses[3] Asymptomatic or symptomatic
Multiple myeloma IgG kappa or lambda; or IgA kappa or gamma Often, multiple lesions of bone Symptomatic

Evaluation of patients with monoclonal (or myeloma) protein (M protein)

Idiotypic myeloma cells can be found in the blood of myeloma patients in all stages of the disease.[4,5] For this reason, when treatment is indicated, systemic treatment must be considered for all patients with symptomatic plasma cell neoplasms. Patients with MGUS or asymptomatic, smoldering myeloma do not require immediate treatment but must be followed carefully for signs of disease progression.

The major challenge is to separate the stable, asymptomatic group of patients who do not require treatment from patients with progressive, symptomatic myeloma who should be treated immediately.[6,7]

Patients with a monoclonal (or myeloma) protein (M protein) in the serum and/or urine are evaluated by some of the following criteria:

  • Measure and follow the serum M protein by serum electrophoresis or by specific immunoglobulin assays; however, specific immunoglobulin quantification always overestimates the M protein because normal immunoglobulins are included in the result. For this reason, baseline and follow-up measurements of the M protein should be done by the same method.[8] Quantitative serum-free light chains may be helpful to follow response if an M protein is not apparent.
  • Measure and follow the amount of M-protein light chains excreted in the urine over 24 hours. Measure the total amount of protein excreted over 24 hours and multiply this value by the percentage of urine protein that is M protein, as determined by electrophoresis of concentrated urine protein. An easier, but less accurate, method uses a spot-urine protein electrophoresis.
  • Identify the heavy and light chain of the M protein by immunofixation electrophoresis.
  • Measure the hemoglobin, leukocyte, platelet, and differential counts.
  • Sometimes, determine the percentage of marrow plasma cells. Be aware that marrow plasma-cell distribution may vary in different sites.
  • Measure serum-free kappa and lambda light chain. This is especially useful in cases of oligosecretory plasma-cell dyscrasia or for following cases of light-chain amyloidosis.[9]
  • Take needle aspirates of a solitary lytic bone lesion, extramedullary tumor(s), or enlarged lymph node(s) to determine whether these are plasmacytomas.
  • Evaluate renal function with serum creatinine and a creatinine clearance.
  • Electrophoresis of concentrated urine protein is very helpful in differentiating glomerular lesions from tubular lesions. Glomerular lesions, such as those resulting from glomerular deposits of amyloid or light-chain deposition disease, result in the nonselective leakage of all serum proteins into the urine; the electrophoresis pattern of this urine resembles the serum pattern with a preponderance of albumin.

    In most myeloma patients, the glomeruli function normally allows only the small molecular weight proteins, such as light chains, to filter into the urine. The concentration of protein in the tubules increases as water is reabsorbed. This leads to precipitation of proteins and the formation of tubular casts, which may injure the tubular cells. With tubular lesions, the typical electrophoresis pattern shows a small albumin peak and a larger light-chain peak in the globulin region; this tubular pattern is the usual pattern found in myeloma patients.

  • Measure serum levels of calcium, alkaline phosphatase, lactic dehydrogenase, and, when indicated by clinical symptoms, cryoglobulins and serum viscosity.
  • Obtain radiographs of the skull, ribs, vertebrae, pelvis, shoulder girdle, and long bones. Whole-body, low-dose, nonenhanced, multidetector-computed tomography and magnetic resonance imaging (MRI) are being evaluated as measures for therapy response monitoring.[10,11] MRI of the spine or long bones is more sensitive in detecting lytic lesions, but any prognostic or therapeutic value for this information remains to be determined.[11]
  • Perform MRI if a paraspinal mass is detected or if symptoms suggest spinal cord or nerve root compression.
  • If amyloidosis is suspected, perform a needle aspiration of subcutaneous abdominal fat and stain the bone marrow biopsy for amyloid as the easiest and safest way to confirm the diagnosis.[12]
  • Measure serum albumin and beta-2-microglobulin as independent prognostic factors.[13,14]
  • A high plasma cell labeling index (≥3%) or the presence of circulating myeloma cells are considered poor prognostic factors.[15] Primary plasma cell leukemia has a particularly poor prognosis.[16]
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