Definition
A.Plasma cell dyscrasias are a group of heterogeneous disorders that stem from the malignant proliferation of monoclonal plasma cells.
Incidence
A.Multiple myeloma (MM) is primarily a disease of the elderly, and the median age at diagnosis is 69.
B.MM represents approximately 1% of all cancers and approximately 10% of all hematologic malignancies.
Pathogenesis
A.Plasma cell dyscrasias arise from the monoclonal proliferation of plasma cells.
Predisposing Factors
A.Although not considered an inherited disease, the risk of developing MM is approximately 3.7-fold higher for persons with a first-degree relative with MM.
B.Twice as common in black persons.
C.Family history increases risk 2- to 4-fold.
D.Occupational exposures may contribute, such as:
1.Pesticides.
2.Petroleum workers.
3.Woodworkers.
4.Leather workers.
5.Ionizing radiation.
Subjective Data
A.Common complaints/symptoms.
1.The clinical presentation for plasma cell dyscrasias is quite variable.
2.Patients with MM often present with signs/symptoms related to plasma cell proliferation in the bone marrow and/or renal dysfunction.
a.Elevated total protein—due to hypersecretion of monoclonal immunoglobulin and light chains; often associated with decreased albumin.
b.Bone involvement—osteolytic lesions, pathologic fractures, hypercalcemia.
c.Anemia.
d.Renal failure.
e.Recurrent infections.
B.Common/typical scenario.
1.Patients may also present with an extramedullary plasmacytoma (soft tissue mass comprised of clonal plasma cells) that can cause spinal cord compression, cauda equina syndrome, severe back pain, paresthesia, and/or radiculopathy.
2.AL amyloidosis can lead to amyloid deposition in any organ, and patients can present with congestive heart failure, renal failure, skin changes, neuropathy, gastroparesis, or diarrhea depending on the organ system(s) involved.
Physical Examination
A.Head and neck: Conjunctival pallor due to anemia; macroglossia.
B.Musculoskeletal: Bone tenderness.
C.Lymphatics: Assess for lymphadenopathy.
D.Neurological: Vertebral compression fractures and/or plasmacytomas can cause neurological deficits if there is spinal cord or nerve compression.
Diagnostic Tests
A.Laboratory data.
1.Complete blood count (CBC) with differential.
2.Comprehensive metabolic panel (CMP) and calcium level.
3.Serum protein electrophoresis with immunofixation electrophoresis (SPEP/IFE).
4.24-hour urine protein electrophoresis with immunofixation electrophoresis (UPEP/IFE)—Bence Jones proteinuria.
5.Serum free light chain assay (kappa and lambda).
6.Serum immunoglobulin levels (IgA, IgG, IgM, IgD).
7.β2-microglobulin for staging and prognostication.
8.Lactate dehydrogenase (LDH) for staging and prognostication.
B.Imaging.
1.Bone survey with plain films to assess for axial and appendicular lytic bone lesions.
2.Consider PET/CT to assess for subtle bone lesions and/or plasmacytomas.
3.Consider MRI of the cervical, thoracic, and lumbar (C/T/L) spine if there is concern for spinal cord compression from extramedullary plasmacytoma or vertebral compression fracture.
C.Bone marrow aspiration and biopsy.
D.Diagnosis.
1.CRAB criteria for symptomatic myeloma.
a.Calcium (hypercalcemia)—serum calcium greater than 11 mg/dL.
b.Renal insufficiency—serum creatinine greater than 2 mg/dL or CrCl less than 40 mL/min.
c.Anemia—hemoglobin less than 10 g/dL.
d.Bone lesions—one or more osteolytic lesions on bone survey, MRI, CT, or PET/CT.
E.Staging.
1.Staging systems for newly diagnosed myeloma patients.
a.Revised International Staging System (R-ISS).
b.Durie-Salmon staging (more subjective and less commonly utilized).
Differential Diagnosis
A.Non-Hodgkin lymphoma (NHL).
B.Amyloidosis.
C.Plasmacytoma.
Evaluation and Management Plan
A.General plan.
1.Treatment depends on the plasma cell dyscrasia.
2.Therapy options for MM and amyloidosis.
a.Patients typically receive two to six cycles of induction systemic chemotherapy followed by autologous stem cell transplant (if eligible) or maintenance chemotherapy (if ineligible for transplant).
b.Systemic chemotherapy.
c.Autologous stem cell transplant.
d.Allogeneic stem cell transplant.
i.Not commonly utilized for MM.
ii.Can be considered for patients with plasma cell leukemia, refractory myeloma, relapsed myeloma, or young patients with high-risk disease (based on fluorescent in situ hybridization [FISH] data).
e.Maintenance chemotherapy.
f.Radiation therapy.
g.Surgical intervention.
i.Vertebroplasty or kyphoplasty may be indicated for patients with vertebral compression fractures.
ii.Excisional biopsy may be performed to confirm plasmacytomas.
B.Supportive care.
1.Bone disease.
a.All patients with osteolytic lesions and/or pathologic fractures should be initiated on IV bisphosphonates.
b.Prior to initiation of bisphosphonate, patients must be evaluated by a dentist to assess for periodontal disease and risk for jaw osteonecrosis.
2.Infectious prophylaxis.
3.Thromboembolic prophylaxis.
4.Pain management.
C.Emergencies and inpatient management.
1.Pain management.
a.Pain is primarily due to skeletal fractures and bone pain from lytic lesions.
b.Pharmacologic therapy.
i.Avoid nonsteroidal anti-inflammatory drugs (NSAIDs) due to nephrotoxicity.
ii.Oral or IV analgesics.
c.Surgical intervention for collapsed vertebral body.
i.Vertebroplasty—injection of bone cement (methyl methacrylate) under fluoroscopy.
ii.Kyphoplasty—placement of inflatable bone tamp prior to injection of bone cement.
2.Hypercalcemia.
a.Due to osteolysis and/or renal failure.
b.Corrected calcium = serum calcium + 0.8 (normal albumin – serum albumin).
c.Rule out other causes (e.g., hyperparathyroidism, thyrotoxicosis, medications, hypervitaminosis D).
d.If asymptomatic and corrected calcium less than 12 mg/dL, patient may not require immediate treatment.
e.Therapeutic intervention.
i.Simultaneous administration of:
1)Hydration—isotonic saline for volume expansion.
2)Calcitonin—dose of 4 international units/kg (IU/kg).
3)Bisphosphonates (e.g., zoledronic acid).
ii.Consider dialysis for patients with severe hypercalcemia.
iii.Repeat serum calcium.
3.Renal failure.
a.Due to light chain deposition in renal tubules (light chain cast nephropathy).
b.Correct electrolyte abnormalities.
c.Careful review of medications and discontinue or dose-adjust nephrotoxic agents.
d.Consider kidney biopsy—stain for Congo red to rule out amyloidosis.
e.IV hydration.
f.Consider dialysis.
4.Tumor lysis syndrome (see sections on Leukemias).
5.Spinal cord compression.
a.Due to vertebral compression fracture and/or plasmacytoma.
b.Symptoms vary depending on the location of compression and may include:
i.Back pain.
ii.Motor deficits.
iii.Paresthesia.
iv.Bowel/bladder incontinence or dysfunction.
v.Gait ataxia.
c.Emergent evaluation with MRI of cervical, thoracic, and/or lumbar spine.
d.If a mass is present, arrange biopsy of lesion for diagnosis.
e.Requires emergent steroids, radiation therapy, and/or neurosurgical decompression.
6.Hyperviscosity syndrome.
a.Symptoms and signs include:
i.Blurred vision.
ii.Papilledema.
iii.Headache.
iv.Neurological symptoms.
v.Oral/nasal bleeding.
vi.Stupor/coma.
b.Obtain IgM and serum viscosity levels.
c.Requires emergent plasmapheresis if symptomatic (not based on serum viscosity level).
Follow-Up
A.Typically includes blood tests, radiologic testing, and bone marrow evaluation every 1 to 3 months.
B.Long-term surveillance varies on a case-by-case basis.
Consultation/Referral
A.Consult medical oncologists and surgical oncologists specializing in MM.