What is the medical work-up and treatment approach for multiple myeloma?

Medical Workup and Treatment Approach for Multiple Myeloma

The diagnostic workup for multiple myeloma requires detection of monoclonal protein, bone marrow plasma cell infiltration assessment, and evaluation of end-organ damage, followed by risk stratification to guide treatment decisions between transplant-eligible and transplant-ineligible approaches. 1, 2

Initial Diagnostic Workup

Laboratory Tests

• Complete blood count with differential and platelet counts 2
• Blood chemistry including BUN, creatinine, serum electrolytes, calcium, albumin, LDH, and beta-2 microglobulin 2
• Quantitative immunoglobulin levels (IgG, IgA, and IgM) 2
• Serum protein electrophoresis (SPEP) and serum immunofixation electrophoresis (SIFE) to detect and characterize M-protein 2
• Serum free light chain (FLC) assay with kappa/lambda ratio 2, 3
• 24-hour urine collection for total protein, urine protein electrophoresis (UPEP), and urine immunofixation electrophoresis (UIFE) 2, 4

Bone Marrow Assessment

• Bone marrow aspiration and biopsy with immunohistochemistry and/or flow cytometry to quantify plasma cell infiltration 2
• Cytogenetic studies including FISH analysis for prognostic markers [del 13, del 17, t(4;14), t(11;14), t(14;16)] 2

Imaging Studies

• Full skeletal survey (X-ray) is the standard imaging modality 2
• MRI provides greater detail and is recommended if spinal cord compression is suspected 2
• CT scan or PET/CT scan may help distinguish between MGUS, smoldering, and overt myeloma 2

Staging and Risk Assessment

• The International Staging System combines β2-microglobulin and serum albumin levels 2, 1
• Cytogenetic abnormalities provide additional prognostic information 2, 1
• Biological parameters of prognostic importance include β2-microglobulin, C-reactive protein, LDH, and serum albumin 2

Treatment Approach

Smoldering (Indolent) Multiple Myeloma

• Immediate treatment is not recommended; observation is the standard approach 2, 1

Transplant-Eligible Patients (generally <65 years, good clinical condition, no renal failure)

• Induction therapy with proteasome inhibitors (bortezomib), immunomodulatory agents (lenalidomide), and dexamethasone 1, 5
• High-dose therapy with autologous stem cell transplantation using peripheral blood progenitor cells 2, 1
• High-dose melphalan 200 mg/m² is the preferred preparative regimen prior to transplantation 2, 1
• Maintenance therapy with lenalidomide or thalidomide to prolong remission 6, 5

Transplant-Ineligible Patients

• Oral combination of melphalan (9 mg/m²/day for 4 days) and prednisone (30 mg/m²/day for 4 days), repeated every 4-6 weeks until stable response 2, 1
• Daratumumab in combination with lenalidomide and dexamethasone (DRd) has shown improved progression-free survival and overall survival compared to lenalidomide and dexamethasone alone 7
• Long-term administration of bisphosphonates (oral or intravenous) to reduce skeletal events 2, 1

Treatment of Relapsed/Refractory Disease

• Regimens similar to those used initially can induce a second remission for relapses after unmaintained remission 1
• Thalidomide, lenalidomide, or bortezomib-based regimens are options for relapsed/refractory disease 1, 6

Response Evaluation

• Assessment of response is based on serum and urine electrophoresis 1, 3
• Complete response requires negative immunofixation of serum and urine, and bone marrow aspiration showing <5% plasma cells 1, 3
• Stringent complete response includes normal FLC ratio and absence of clonal plasma cells in bone marrow 3, 7

Common Pitfalls and Caveats

• Multiagent chemotherapy has not proven superior and may be even inferior in elderly patients 2, 1
• Random urine samples are insufficient and cannot replace a 24-hour urine collection for protein electrophoresis 4
• When monitoring response with free light chain assays, it's crucial to use the same test for serial measurements to ensure accurate relative quantification 1, 3
• Inadequate concentration of urine samples may reduce sensitivity for detecting low levels of monoclonal proteins 4
• Spinal cord compression requires immediate intervention with high-dose dexamethasone, surgical decompression if due to bone fragments, and local radiotherapy 1