From the Guidelines
Multiple myeloma diagnosis requires a combination of blood tests, urine tests, bone marrow biopsy, and imaging studies, with diagnostic criteria including evidence of clonal bone marrow plasma cells ≥10% or biopsy-proven plasmacytoma, plus at least one myeloma-defining event, as outlined by the International Myeloma Working Group (1). The diagnostic process typically involves:
- Initial testing, including complete blood count, comprehensive metabolic panel, serum protein electrophoresis with immunofixation, serum free light chain assay, 24-hour urine protein electrophoresis, and beta-2 microglobulin
- Bone marrow aspiration and biopsy to confirm the diagnosis by demonstrating clonal plasma cells
- Imaging studies, such as skeletal survey, whole-body low-dose CT, MRI, or PET-CT, to identify bone lesions The myeloma-defining events include:
- End-organ damage (CRAB features: hypercalcemia, renal insufficiency, anemia, or bone lesions) attributable to the underlying plasma-cell disorder
- Clonal bone marrow plasma cells ≥60%
- Serum involved to uninvolved free light chain (FLC) ratio ≥100 (provided involved FLC level is ≥100 mg/L)
- More than one focal lesion (5 mm or more in size) on magnetic resonance imaging (MRI) Once diagnosed, patients should be staged using the Revised International Staging System (R-ISS), which incorporates serum albumin, beta-2 microglobulin, LDH levels, and high-risk cytogenetic abnormalities to guide treatment decisions and provide prognostic information (1). The most recent guidelines from the International Myeloma Working Group (1) provide the foundation for diagnosis and staging, and should be used in conjunction with other relevant studies (1) to inform treatment decisions.
From the Research
Diagnosis of Multiple Myeloma
- Multiple myeloma is a hematologic malignancy characterized by the presence of abnormal clonal plasma cells in the bone marrow, with potential for uncontrolled growth causing destructive bone lesions, kidney injury, anemia, and hypercalcemia 2.
- The disease is diagnosed with serum or urine protein electrophoresis or immunofixation and bone marrow aspirate analysis 3.
- Evaluation of patients with possible multiple myeloma includes measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels; serum protein electrophoresis with immunofixation; 24-hour urine protein electrophoresis; and full-body skeletal imaging with computed tomography, positron emission tomography, or magnetic resonance imaging 2.
Staging and Prognosis
- The Revised International Staging System combines data from the serum biomarkers β2 microglobulin, albumin, and lactate dehydrogenase in conjunction with malignant plasma cell genomic features to assess estimated progression-free survival and overall survival 2.
- At diagnosis, 28% of patients are classified as having Revised International Staging stage I multiple myeloma, and these patients have a median 5-year survival of 82% 2.
- The staging system has been revised to combine both measures of tumor burden and disease biology 4.
Treatment
- Standard first-line (induction) therapy consists of a combination of an injectable proteasome inhibitor, an oral immunomodulatory agent, and dexamethasone and is associated with median progression-free survival of 41 months 2.
- Induction therapy combined with autologous hematopoietic stem cell transplantation followed by maintenance lenalidomide is standard of care for eligible patients 2.
- New drugs introduced in the past few years include carfilzomib, pomalidomide, panobinostat, ixazomib, elotuzumab, and daratumumab 4.
Role of Serum Protein Electrophoresis
- Serum protein electrophoresis is used to identify patients with multiple myeloma and other serum protein disorders 5.
- A homogeneous spike-like peak in a focal region of the gamma-globulin zone indicates a monoclonal gammopathy 5.
- Serum protein electrophoresis is an easy to perform laboratory test which can be used for detection and quantification of monoclonal gammopathy and should be recommended as preliminary test for suspected cases of multiple myeloma 6.