From the Guidelines
The workup for multiple myeloma involves a comprehensive approach starting with blood tests including complete blood count, comprehensive metabolic panel, serum protein electrophoresis, serum free light chain assay, and beta-2 microglobulin, as recommended by the most recent guidelines 1. The initial diagnostic workup should include a history and physical examination, and the following baseline blood studies and biological assessments to differentiate symptomatic and asymptomatic MM:
- a CBC with differential and platelet counts
- blood urea nitrogen (BUN)
- serum creatinine and serum electrolytes
- serum calcium
- albumin
- lactate dehydrogenase (LDH)
- and beta-2 microglobulin, as outlined in the NCCN guidelines 1. Urine studies should include a 24-hour urine collection for protein electrophoresis, and imaging is essential, with a skeletal survey or low-dose whole-body CT scan to identify bone lesions, as recommended by the ESMO guidelines 1. Bone marrow biopsy is required to confirm the diagnosis, typically showing >10% clonal plasma cells, and additional testing includes fluorescence in situ hybridization (FISH) to detect cytogenetic abnormalities that impact prognosis, as stated in the NCCN guidelines 1. Patients should also undergo assessment for end-organ damage using the CRAB criteria (hypercalcemia, renal insufficiency, anemia, and bone lesions), and MRI may be indicated if spinal cord compression is suspected, as noted in the NCCN guidelines 1. PET-CT can be useful to evaluate disease activity and identify extramedullary disease, and this comprehensive workup allows for accurate diagnosis, staging according to the Revised International Staging System (R-ISS), and helps guide treatment decisions based on risk stratification, as recommended by the most recent guidelines 1. Early consultation with hematology-oncology is recommended as soon as multiple myeloma is suspected, to ensure timely and appropriate management of the disease. Some key points to consider in the workup of multiple myeloma include:
- The importance of using the same test for serial studies to ensure accurate relative quantification of the myeloma or M-protein, as noted in the NCCN guidelines 1.
- The use of serum free light chain (FLC) assay along with serum protein electrophoresis and serum immunofixation electrophoresis to yield high sensitivity while screening for MM and related plasma cell disorders, as recommended by the NCCN guidelines 1.
- The role of FISH in detecting cytogenetic abnormalities, such as deletions and translocations, which can impact prognosis and guide treatment decisions, as stated in the ESMO guidelines 1.
- The importance of assessing for end-organ damage using the CRAB criteria, to guide treatment decisions and monitor disease progression, as noted in the NCCN guidelines 1.
From the Research
Diagnosis of Multiple Myeloma
To diagnose multiple myeloma, several tests are used, including:
- Measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels 2
- Serum protein electrophoresis with immunofixation 2, 3, 4, 5
- 24-hour urine protein electrophoresis 2, 6
- Full-body skeletal imaging with computed tomography, positron emission tomography, or magnetic resonance imaging 2
Staging of Multiple Myeloma
The Revised International Staging System is used to assess estimated progression-free survival and overall survival, combining data from serum biomarkers β2 microglobulin, albumin, and lactate dehydrogenase, as well as malignant plasma cell genomic features 2
Treatment of Multiple Myeloma
Standard first-line therapy consists of a combination of an injectable proteasome inhibitor, an oral immunomodulatory agent, and dexamethasone, followed by autologous hematopoietic stem cell transplantation and maintenance lenalidomide for eligible patients 2
- Induction therapy with an injectable proteasome inhibitor, an oral immunomodulatory agent, and dexamethasone is associated with median progression-free survival of 41 months 2
Monitoring of Multiple Myeloma
Response criteria for multiple myeloma are based on changes in monoclonal protein levels quantified using serum and/or urine protein electrophoresis 6