Multiple Myeloma Laboratory Orders
Initial Diagnostic Laboratory Workup
For a patient with suspected multiple myeloma, order a comprehensive panel including complete blood count, comprehensive metabolic panel with calcium, serum and urine protein studies, serum free light chains, beta-2 microglobulin, LDH, bone marrow evaluation with cytogenetics, and skeletal imaging. 1, 2
Blood Tests
Complete blood count (CBC) with differential and peripheral blood smear to assess for anemia (normochromic, normocytic), rouleaux formation, and circulating plasma cells 1, 2
Comprehensive chemistry panel including:
Serum protein electrophoresis (SPEP) with immunofixation using agarose gel or capillary zone electrophoresis to detect and characterize monoclonal protein 1, 2
Nephelometric quantification of immunoglobulins (IgG, IgA, IgM) to measure monoclonal protein concentration and assess uninvolved immunoglobulin suppression 1, 2
Serum free light chain (FLC) assay with kappa/lambda ratio for screening and monitoring, particularly critical in light chain and nonsecretory myeloma 1, 2
Beta-2 microglobulin for International Staging System prognostication and tumor burden assessment 1, 2
Lactate dehydrogenase (LDH) for independent prognostic significance 1, 2
Urine Tests
Routine urinalysis for initial screening 1
24-hour urine collection for total protein, protein electrophoresis (UPEP), and immunofixation (UIFE) to quantify and characterize urinary monoclonal protein (Bence Jones protein) 1, 2
Critical pitfall: A 24-hour urine collection cannot be replaced by a random morning urine sample or spot urine protein-to-creatinine ratio for initial diagnosis 1, 2. Immunofixation must be performed even if no measurable protein peak is detected on electrophoresis 1.
Bone Marrow Evaluation
Unilateral bone marrow aspirate and/or biopsy to confirm ≥10% clonal plasma cells required for diagnosis 1, 2
CD138 immunoperoxidase or immunofluorescence staining to accurately determine plasma cell percentage and establish clonality 1
Standard metaphase cytogenetics to separate hyperdiploid from nonhyperdiploid patients and detect uncommon chromosomal abnormalities (20% yield) 1
Fluorescence in situ hybridization (FISH) on plasma cell-sorted specimens with probes for high-risk abnormalities: del(17p13), t(4;14), t(14;16), and t(14;20) 1, 2
Important consideration: Both aspirate and biopsy should be performed when possible, as biopsy provides more reliable assessment of plasma cell infiltration and avoids need for repeat procedures if aspirate is inadequate 1.
Imaging Studies
Skeletal survey including posteroanterior chest, anteroposterior and lateral views of cervical/thoracic/lumbar spine, skull, humeri, femora, and anteroposterior pelvis to detect lytic lesions 1, 2
MRI of spine and pelvis is mandatory for all patients with presumed solitary plasmacytoma and should be considered in smoldering myeloma to detect occult lesions that predict rapid progression 1
Whole-body low-dose CT, MRI, or PET/CT as clinically indicated for superior detection of bone lesions and extramedullary disease 2, 3
Ongoing Monitoring Laboratory Orders
For Active Myeloma in Remission
Monitor every 3-6 months with CBC, comprehensive metabolic panel, quantitative immunoglobulins, SPEP with immunofixation, and serum free light chains. 3, 4
Serum chemistry including creatinine, albumin, calcium, LDH, and beta-2 microglobulin 3, 4
Serum quantitative immunoglobulins to track disease burden 3, 4
SPEP and immunofixation to detect and quantify monoclonal protein 3, 4
Serum free light chain assay with kappa/lambda ratio to track disease progression 3, 4
24-hour urine protein electrophoresis and immunofixation for patients with measurable urinary M-protein (serum FLC cannot replace this) 2, 3
Annual skeletal survey or whole-body low-dose CT for bone surveillance 3, 4
For Suspected Disease Progression or Relapse
Increase monitoring frequency to every 4 weeks initially and perform comprehensive reassessment including bone marrow examination with cytogenetics/FISH and advanced imaging. 3, 4
All baseline laboratory tests as listed above, performed more frequently 3
Bone marrow aspirate and biopsy with repeat cytogenetics/FISH to confirm progression and reassess risk stratification 3, 4
MRI and/or CT and/or PET/CT for evaluation of bone lesions and extramedullary disease 3, 4
Special Circumstances Requiring Additional Testing
Serum viscosity and fundoscopy when hyperviscosity symptoms are present 3
Lumbar puncture (cell counts, chemistry, cytology, immunophenotyping) for suspected leptomeningeal involvement 3
Evaluation for AL amyloidosis (fat pad biopsy, cardiac biomarkers, echocardiography) when clinically indicated 3
Coagulation studies (bleeding time, APTT, PT) for suspected bleeding disorders 3
Cryoglobulins and Coombs test for suspected cold autoantibody 3
Key Pitfalls to Avoid
Do not rely solely on serum free light chains for monitoring patients with measurable urinary M-proteins—24-hour urine collections remain essential. 2, 3 Renal impairment causes decreased clearance of both kappa and lambda free light chains, potentially leading to false elevations 2.
Do not perform urine-free light chain assays—they are not validated for clinical use. 1, 2
Do not overlook nonsecretory myeloma (approximately 3% of cases)—these patients require bone marrow examination for monitoring since neither serum nor urine proteins are measurable. 2
Ensure FISH is performed on plasma cell-sorted specimens or with simultaneous cytoplasmic immunoglobulin staining (cIg-FISH), as standard FISH on unsorted bone marrow has inadequate sensitivity. 3