What are the typical symptoms and investigations to order when suspecting multiple myeloma?

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Last updated: June 9, 2025View editorial policy

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From the Guidelines

Multiple myeloma typically presents with symptoms captured by the CRAB criteria: hypercalcemia, renal insufficiency, anemia, and bone lesions, and when suspecting this condition, essential investigations should include a complete blood count, serum calcium, creatinine, and albumin levels, as well as protein studies such as serum protein electrophoresis, immunofixation, and serum free light chain assay.

Typical Symptoms

The symptoms of multiple myeloma can vary but often include:

  • Bone pain, particularly in the back or ribs
  • Fatigue
  • Recurrent infections
  • Unexplained weight loss
  • Neurological symptoms from spinal cord compression

Investigations to Order

When suspecting multiple myeloma, the following investigations should be ordered:

  • Complete blood count (CBC) with differential and platelet counts to look for anemia 1
  • Serum studies:
    • Serum calcium
    • Serum creatinine and serum electrolytes
    • Serum albumin
    • Lactate dehydrogenase (LDH)
    • Beta-2 microglobulin
    • Quantitative immunoglobulin levels (IgG, IgA, and IgM)
    • Serum protein electrophoresis
    • Serum immunofixation electrophoresis
    • Serum free light chain (FLC) assay
  • Urine studies:
    • 24-hour urine protein electrophoresis
    • Urine protein electrophoresis
    • Urine immunofixation electrophoresis
  • Imaging studies:
    • Full skeleton radiographic survey or whole-body, low-dose CT to evaluate lytic bone lesions
    • MRI or PET-CT for better sensitivity
  • Bone marrow aspiration and biopsy to evaluate bone marrow plasma cell infiltration and to detect quantitative and/or qualitative abnormalities of bone marrow plasma cells 1 Additional tests, such as cytogenetic studies on bone marrow samples, can help identify high-risk genetic abnormalities 1.

These comprehensive investigations allow for accurate diagnosis, staging, and risk stratification of multiple myeloma, guiding appropriate treatment decisions, as recommended by the NCCN Guidelines for MM 1.

From the Research

Typical Symptoms of Multiple Myeloma

  • Bone pain
  • Nonspecific symptoms such as nausea, vomiting, malaise, weakness, recurrent infections, and weight loss 2
  • Anemia, renal disease, and elevated protein levels 2
  • Destructive bone lesions, kidney injury, anemia, and hypercalcemia 3

Investigations to Order When Suspecting Multiple Myeloma

  • Complete blood count with differential
  • Serum chemistries
  • Creatinine, lactate dehydrogenase, and beta2-microglobulin tests
  • Immunoglobulin studies
  • Skeletal survey
  • Bone marrow evaluation 2
  • Measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels
  • Serum protein electrophoresis with immunofixation
  • 24-hour urine protein electrophoresis
  • Full-body skeletal imaging with computed tomography, positron emission tomography, or magnetic resonance imaging 3
  • Serum protein electrophoresis to detect and quantify monoclonal gammopathy 4, 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Multiple Myeloma: Diagnosis and Treatment.

American family physician, 2017

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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