Multiple Myeloma Treatment Information for Healthcare Professionals

Stage Information

Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. Refer to the PDQ levels of evidence summary for more information.

Multiple myeloma

Stage I multiple myeloma means all of the following:

1. Hemoglobin greater than 10 g/dL.
   
2. Normal serum calcium.
   
3. Normal bone structure.
   
4. Low M-protein production as shown by:

   a. IgG less than 5.0 g/dL
   b. IgA less than 3.0 g/dL
   c. urinary kappa or lambda less than 4 g/24 hours

Estimated myeloma cell mass: less than 0.6 trillion cells per square meter (low burden)

The following subclassification of stages is used:

A. creatinine less than 2.0 mg/dL
B. creatinine greater than or equal to 2.0 mg/dL

Impaired renal function worsens prognosis regardless of stage.

Stage II multiple myeloma means multiple myeloma that fits in neither stage I nor stage III.

Estimated myeloma cell mass: 0.6 to 1.2 trillion cells per square meter (intermediate burden)

The following subclassification of stages is used:

A. creatinine less than 2.0 mg/dL
B. creatinine greater than or equal to 2.0 mg/dL

Impaired renal function worsens prognosis regardless of stage.

Stage III multiple myeloma means one or more of the following:

1. Hemoglobin less than 8.5 g/dL.
   
2. Serum calcium greater than 12.0 mg/dL.
   
3. More than 3 lytic bone lesions.
   
4. High M-protein production as shown by:

   a. IgG greater than 7.0 g/dL
   b. IgA greater than 5.0 g/dL
   c. urinary kappa or lambda greater than 12.0 g/24 hours

Estimated myeloma cell mass: greater than 1.2 trillion cells per square meter (high burden)

The following subclassification of stages is used:

A. creatinine less than 2.0 mg/dL
B. creatinine greater than or equal to 2.0 mg/dL

Serum beta-2 microglobulin has been shown to be a reliable marker for prognosis.¹ Since the great majority of symptomatic myeloma patients are classified as stage III by the Durie/Salmon criteria, this staging system has not proven to be very useful for identifying the patients with intermediate and poor prognosis. Many investigators favor a simpler system using only beta-2 microglobulin and albumin concentrations to stage patients.² Impaired renal function worsens prognosis regardless of stage. Abnormalities of chromosomes 13 and 11q and plasmablastic morphology appear to have predicted poor outcome for a population of patients whose myeloma was treated with high-dose chemotherapy and stem cell rescue.^3,4

Isolated plasmacytoma of bone

If a solitary lytic lesion of plasma cells is found on skeletal survey in an otherwise asymptomatic patient and a bone marrow examination from an uninvolved site contains less than 5% plasma cells, the patient has an isolated plasmacytoma of bone. About 25% of patients have a serum and/or urine M- protein; this should disappear following adequate irradiation of the lytic lesion. When clinically indicated, magnetic resonance imaging (MRI) may reveal unsuspected bony lesions which were undetected on standard radiographs.⁵

Extramedullary plasmacytoma

Patients with isolated plasma cell tumors of soft tissues, most commonly occurring in the tonsils, nasopharynx, or paranasal sinuses, should have skeletal x-rays and bone marrow biopsy. If these tests are negative, the patient has extramedullary plasmacytoma. About 25% of patients have serum and/or urine M-protein; this should disappear following adequate irradiation.

Macroglobulinemia

Macroglobulinemia is a proliferation of plasmacytoid lymphocytes secreting an IgM M-protein. Patients often have lymphadenopathy and hepatosplenomegaly, but bony lesions are uncommon. There is no generally accepted staging system.

The term macroglobulinemia describes an increase in the serum concentration of a monoclonal IgM.^6,7 Most patients are asymptomatic and do not require treatment. The most common symptoms and signs, when they develop, are fatigue, manifestations of hyperviscosity (headache, epistaxis, visual disturbances), and neurologic abnormalities. Lymphadenopathy and splenomegaly are found in about one third of patients. The increased intravascular concentration of high molecular weight IgM leads to an expansion of the plasma volume, a dilutional anemia, and in extreme cases, congestive heart failure. Sludging of the blood can be seen in conjunctival and retinal veins with dilatation and segmentation of vessels ("link sausage" appearance), retinal hemorrhages, and papilledema. Similar problems with the circulation of blood in the CNS can cause ataxia, nystagmus, vertigo, confusion, and disturbances of consciousness.

The various disorders associated with the appearance of a monoclonal IgM include:

1. Monoclonal Gammopathy of Undetermined Significance (MGUS). Patients are asymptomatic, the M-protein is relatively stable, and there is no lymphadenopathy, splenomegaly, or bony lesions.
   
2. Waldenstrom's Macroglobulinemia (WM). Patients are symptomatic, have lymphoplasmacytic marrow infiltration and a rising serum IgM concentration, and may have lymphadenopathy or splenomegaly. Rarely, patients with WM have lytic bone lesions. See the PDQ summary on adult non-Hodgkin's lymphoma for more information.
   
3. Absolute lymphocyte count exceeding 5,000 cells per cubic millimeter. The patient may be classified as having chronic lymphocytic leukemia (CLL) if the lymphocytes are of the small, well-differentiated variety. CLL must be differentiated from the lymphoplasmacytosis that may occur as a peripheral blood manifestation of WM.
   
4. Lymphoplasmacytic lymphoma. When a lymph node biopsy demonstrates the pathologic characteristic of a lymphoma, this becomes the diagnosis.
   
5. Chronic cold agglutinin disease. Patients have a high cold agglutinin titer and no morphologic evidence of neoplasia. These patients often have a hemolytic anemia that is aggravated by cold exposure. The IgM has kappa light chains in more than 90% of these patients.

Monoclonal gammopathy of undetermined significance

Patients with MGUS have an M-protein in the serum without findings of multiple myeloma, macroglobulinemia, amyloidosis, or lymphoma and with fewer than 10% plasma cells in the bone marrow. These patients are asymptomatic and should not be treated. They must, however, be followed carefully since about 2% per year will progress to develop one of the symptomatic B-cell neoplasms and may then require therapy.⁸

References:

1. Durie BG, Stock-Novack DL, Salmon SE, et al: Prognostic value of pretreatment serum beta-2 microglobulin in myeloma: A Southwest Oncology Group Study. Blood 75(4): 823-830, 1990.
2. Bataille R, Grenier J, Sany J: Beta-2-microglobulin in myeloma: optimal use for staging, prognosis, and treatment: a prospective study of 160 patients. Blood 63(2): 468-476, 1984.
3. Tricot G, Barlogie B, Jagannath S, et al.: Poor prognosis in multiple myeloma is associated only with partial or complete deletions of chromosome 13 or abnormalities involving 11q and not with other karyotype abnormalities. Blood 86(11): 4250-4256, 1995.
4. Rajkumar SV, Fonseca R, Lacy MQ, et al.: Plasmablastic morphology is an independent predictor of poor survival after autologous stem-cell transplantation for multiple myeloma. Journal of Clinical Oncology 17(5): 1551-1557, 1999.
5. Moulopoulos LA, Dimopoulos MA, Weber D, et al.: Magnetic resonance imaging in the staging of solitary plasmacytoma of bone. Journal of Clinical Oncology 11(7): 1311-1315, 1993.
6. Kyle RA, Garton JP: The spectrum of IgM monoclonal gammopathy in 430 cases. Mayo Clinic Proceedings 62(8): 719-731, 1987.
7. Bergsagel DE: Monoclonal macroglobulinemia. In: Foley JF, Vose JM, Armitage JO, Eds.: Current Therapy in Cancer. Philadelphia: Saunders, 1994, pp 304-307.
8. Blade J, Kyle RA: Monoclonal gammopathies of undetermined significance. In: Malpas JS, Bergsagel DE, Kyle RA, et al. eds.: Myeloma: Biology and Management. 2nd ed., Oxford, England: Oxford University Press, 1998, pp 513-544.

   Back to Content Page                                   Next >>