6. Multiple Myeloma

7/27/2019 6. Multiple Myeloma

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Multiple Myeloma:

Diagnosis and TreatmentKonradC.nau,Md,WilliaMd.leWis,Md,West Virginia University Department o Family MedicineEastern Division, Harpers Ferry, West Virginia

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Multiple myeloma, the most common bone malignancy, is occurring with increasing requency in older persons.

Typical symptoms are bone pain, malaise, anemia, renal insuciency, and hypercalcemia. Incidental discovery on

comprehensive laboratory panels is common. The disease is diagnosed with serum or urine protein electrophore-

sis or immunoxation and bone marrow aspirate analysis. Skeletal radiographs are important in staging multiple

myeloma and revealing lytic lesions, vertebral compression ractures, and osteoporosis. Magnetic resonance imag-

ing and positron emission tomography or computed tomography are emerging as useul tools in the evaluation o

patients with myeloma; magnetic resonance imaging is preerred or evaluating acute spinal compression. Nuclear

bone scans and dual energy x-ray absorptiometry have no role in the diagnosis and staging o myeloma. The dier-ential diagnosis o monoclonal gammopathies includes monoclonal gammopathy o uncertain signicance, smolder-

ing (asymptomatic) and symptomatic multiple myeloma, amyloidosis, B-cell non-Hodgkin lymphoma, Waldenstrm

macroglobulinemia, and rare plasma cell leukemia and heavy chain diseases. Patients with monoclonal gammopathy

o uncertain signicance or smoldering multiple myeloma should be ollowed closely, but not treated. Symptom-

atic multiple myeloma is treated with chemotherapy ollowed by autologous stem cell transplantation, i possible.

Melphalan, prednisolone, dexamethasone, vincristine, doxorubicin, bortezomib, and thalidomide and its analogue

lenalidomide have been used successully. It is important that amily physicians recognize and appropriately treat

multiple myeloma complications. Bone pain is treated with opiates, bisphosphonates, radiotherapy, vertebroplasty,

or kyphoplasty; nephrotoxic nonsteroidal anti-infammatory drugs should be avoided. Hypercalcemia is treated with

isotonic saline inusions, steroids, urosemide, or bisphosphonates. Because o susceptibility to inections, patients

require broad-spectrum antibiotics or ebrile illness and immunization against infuenza, pneumococcus, and

Haemophilus infuenzaeB. Five-year survival rates approach 33 percent, and the median survival rate is 33 months.(Am Fam Physician. 2008;78(7):853-859, 860. Copyright 2008 American Academy o Family Physicians.)

Patient information:

A handout on multiplemyeloma, written by theauthors of this article, isprovided on page 860.

Downloaded from the American Family Physician Web site at www. aafp.org/afp. C opyright 2008 A merican A cademy of Family Physicians. For the private, noncommercial

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854 American Family Physician www.p.g/p Volume 78, Number 7 October 1, 2008

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SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendations

Evidence

rating

Reerences

Serum and urine protein electrophoresis and immunoxation should be obtained or the diagnosis

o multiple myeloma.

C 6, 10, 11

Nuclear bone scans and dual energy x-ray absorptiometry have no role in the diagnosis

o multiple myeloma.

C 6

Smoldering (asymptomatic) multiple myeloma should not be treated. A 16Monitor or multiple myeloma symptoms and M protein (serum and urine) every six to 12 months

in patients with monoclonal gammopathy o undetermined signicance, and every three to our

months in patients with smoldering multiple myeloma.

C 3, 6, 16

Avoid using nonsteroidal anti-infammatory drugs when treating pain in patients with multiple

myeloma.

C 6

Bisphosphonates should be prescribed or all patients with symptomatic multiple myeloma. A 6, 21

Patients with multiple myeloma should receive infuenza, pneumococcus, and Haemophilus

inuenzae B vaccinations.

B 6, 29

A = consistent, good-quali ty patient-oriented ev idence; B = inconsistent or limited-qual ity patient-oriented ev idence; C = consensus, disease-

oriented evidence, usual practice, expert opinion, or case series. For inormation about the SORT evidence rating system, go to http://www.

aap.org/apsort.xml.

Heavy chain

ILLUSTRATION

BY

ReNeeCANNON

Figure 1. Normal immunoglobulin molecule containingpaired heavy chains with one smaller light chain attachedto each.

Antigen binding sites

Light chain

Antigen binding sites


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Multiple Myeloma

October 1, 2008 Volume 78, Number 7 www.p.g/p American Family Physician 855

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Figure 2. Origins o plasma cells. Like most blood cells, plasma cellsdevelop rom stem cells in the bone marrow. Stem cells can developinto B cells (B lymphocytes), which travel to the lymph nodes, mature,and then travel throughout the body. When oreign substances (anti-gens) enter the body, B cells develop into plasma cells that produceimmunoglobulins (antibodies) to help fght inection and disease.

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ILLUSTRAT

ION

BY

ReNeeCANNON

Table 1. Incidence of Presenting Symptoms

in Patients with Multiple Myeloma

Symptom Incidence (%)

Bone pain (especially back pain) 58

Fatigue (typically caused by anemia) 32

Pathologic racture 26 to 34

Weight loss 24

Paresthesias 5

Fever 0.7

None (asymptomatic) 34

Inormation rom reerences 5 and 7.

Antibodiesreleased

Plasma cell


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Multiple Myeloma


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Table 2. Presenting Diagnostic Abnormalitiesin Patients with Multiple Myeloma

Abnormalit y

Percentage o

patients with the

abnormality

M protein (serum or urine) 97

Serum M protein

Electrophoresis 82

Immunoxation 93

Urine M protein 75

10 percent or more bone marrow

plasma cells

90

Bone lesions on radiography (lytic lesions,

66 percent o patients; ractures,

26 percent; osteoporosis, 23 percent;blastic/sclerotic lesions, 0.5 percent)

75

Hemoglobin level o 12 g per dL

(120 g per L) or less

65

Serum creatinine level o

2 mg per dL (180 mol per L) or greater

23

Serum calcium level o 11 mg per dL (2.75

mmol per L) or greater

13

Adapted with permission rom Kyle RA. The monoclonal gammopa-

thies. Clin Chem. 1994;40(11 pt 2):2159, with additional inormation

rom reerence 5.


5/7


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Table 3. Differential Diagnosis of Monoclonal Gammopathies

Monoclonal

gammopathy Incidence Serum fndings Bone marrow fndings Clinical c lues

MGUS3 1 to 2 per 100

adults older

than 50 years

M protein level o less

than 3 g per dL (30 g

per L)

Less than 10 percent plasma cells Absence o myeloma-

related organ and tissue

impairment

Smoldering(asymptomatic)

multiple myeloma5,10

5 to 7 per1,000,000

M protein level o 3 gper dL or greater (IgG,

IgA, IgM, IgD, or ree

light chains)

10 percent or more plasma cells Absence o myeloma-related organ and tissue

impairment

Symptomatic multiple

myeloma6,105 to 7 per

100,000

M proteins (40 percent

o patients with

multiple myeloma have

a level less than 3 g

per dL)

Plasma cells (5 percent o

patients with multiple myeloma

have ewer than 10 percent

plasma cells)

Presence o at least one

myeloma-related organ

and tissue impairment

Waldenstrm

macroglobulinemia107 to 10 per

1,000,000

IgM Biopsy ndings are hypercellular

with lymphocytes, plasma cells,

and lymphoplasmacytoid cells

Epistaxis; vision, retinal,

or neurologic problems

Amyloidosis2,10,12 5 to 13 per1,000,000

Ig light chains Less than 10 percent plasmacells, Congo red amyloid bone

marrow deposits (60 percent

o patients)

Congestive heart ailure,gastrointestinal

symptoms, peripheral

neuropathy

B-cell non-Hodgkin

lymphoma119 per 100,000

adults

May have elevated

M protein levels

Variable abnormal lymphocytes Lymphadenopathy, ever,

pruritus

Plasmacytoma5,10 Rare Extramedullary, IgA

M protein

Solitary bone or sot tissue

plasmacytoma shows plasma

cells in the tumor; otherwise,

there is no evidence o multiple

myeloma in the bone marrow

Bone pain (spine or long

bone), extramedullary

(80 percent o cases are

located in the upper

respiratory tract)

Plasma cell leukemia10 Rare Low M protein levels,

but more than 20percent plasma cells in

peripheral blood smear

More than 10 percent plasma

cells (occurs de novo or withknown multiple myeloma)

Lymphadenopathy,

hepatosplenomegaly

Heavy chain diseases10 Very rare Incomplete heavy chains

without light chains

Variable lymphocytes, plasma

cells, lymphoplasmacytoid cells

Variable, depending

on disease type (, ,

or ); autoimmune

disease, malabsorption,

lymphadenopathy,

uvula or palatal edema

Ig = immunoglobulin; MGUS = monoclonal gammopathy o uncertain signifcance.

Inormation rom reerences 1 through 3, 5, 6, 9, 10, and 12.


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Multiple Myeloma


Complications of Multiple Myeloma

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The Authors

KONRAD C. NAU, MD, FAAFP, is a professor in and chair of the Depart-ment of Family Medicine, Eastern Division, at the West Virginia UniversitySchool of Medicine in Harpers Ferry. He also is director of the universitysGeriatric Medicine Fellowship Program. Dr. Nau received his medical

degree from the West Virginia University School of Medicine and com-pleted his family medicine residency at West Virginia University Hospitalin Morgantown.

WILLIAM D. LEWIS, MD, is clinical assistant professor of family medicineof the E.A. Hawse Health CenterMathias (W.V.) Branch. He received hismedical degree from West Virginia University School of Medicine in Mor-gantown and completed the Clarksburg (W.V.) Family Practice ResidencyProgram. He also completed a fellowship in rural medicine from West Vir-ginia University.

Address correspondence to Konrad C. Nau, MD, FAAFP, West VirginiaUniversity, Dept. of Family Medicine, Eastern Division, 171 Taylor St.,Harpers Ferry, WV 26425 (e -mail: [email protected]). Reprints arenot available from the authors.

Author disclosure: Nothing to disclose.

Table 4. International Staging Systemfor Multiple Myeloma

Stage Criteria

Percentage

o patients in

this stage

Median

survival

(months)

I Serum 2-microglobulin level less than

3.5 mg per L (297 nmol per L)

Serum albumin level o 3.5 g per dL

(35 g per L) or greater

28 62

II Not stage I or III 33 45

III Serum 2-microglobulin level o 5.5

mg per L (466 nmol per L) or greater

39 29

Adapted with permission rom Greipp PR, San Migue l J, Durie BG, et al. Internat ional

staging system or multiple myeloma [published correction appears in J Clin Oncol.

2005;23(25):6281]. J Clin Oncol. 2005;23(15):3415.


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Multiple Myeloma


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6. Multiple Myeloma