Diagnostic and Response Criteria for Light Chain Multiple Myeloma
Light chain multiple myeloma requires specific diagnostic criteria including elevated serum free light chains, clonal bone marrow plasma cells ≥10%, and evidence of end-organ damage, with response assessment primarily monitored through serum free light chain measurements. 1
Diagnostic Criteria for Light Chain Multiple Myeloma
Essential Diagnostic Tests
- Complete blood count with differential and platelet counts 1
- Blood chemistry including BUN, creatinine, electrolytes, calcium, albumin, LDH, and beta-2 microglobulin 1
- Serum free light chain (FLC) assay with kappa/lambda ratio 1
- 24-hour urine collection for total protein, urine protein electrophoresis (UPEP), and urine immunofixation electrophoresis (UIFE) 1
- Bone marrow aspiration and biopsy with immunohistochemistry and/or flow cytometry 1
- Cytogenetic studies including FISH analysis 1
- Skeletal survey (X-ray, CT, or MRI) 1
Specific Diagnostic Criteria
- ≥10% clonal bone marrow plasma cells or biopsy-proven plasmacytoma 1
- Absence of monoclonal intact immunoglobulin on serum protein electrophoresis (no M-spike) 2
- Abnormal serum free light chain ratio with elevated involved light chain 1
- Evidence of end-organ damage (CRAB criteria) 1:
- Hypercalcemia: serum calcium >11 mg/dL
- Renal insufficiency: creatinine >2 mg/dL or clearance <40 mL/min
- Anemia: hemoglobin <10 g/dL
- Bone lesions: lytic lesions on skeletal radiography, CT, or MRI
Biomarkers of Malignancy (Any One)
- ≥60% clonal bone marrow plasma cells 1
- Involved/uninvolved serum FLC ratio ≥100 (with involved FLC ≥10 mg/dL) 1, 3
1 focal lesion on MRI studies (each focal lesion must be ≥5 mm in size) 1
Response Criteria for Light Chain Multiple Myeloma
Serum Free Light Chain Monitoring
- Primary method for monitoring light chain myeloma due to greater sensitivity than urine electrophoresis 4, 5
- Provides earlier detection of response (median 1.94 months) compared to serum protein electrophoresis (median 5.39 months) 6
- Shows greater concordance with bone marrow plasma cell assessments and beta-2 microglobulin 5
International Myeloma Working Group Response Criteria
Stringent Complete Response (sCR) 1:
- Complete response criteria plus
- Normal FLC ratio and
- Absence of clonal plasma cells in bone marrow by immunohistochemistry or flow cytometry
Complete Response (CR) 1:
- Negative immunofixation of serum and urine
- Disappearance of any soft tissue plasmacytomas
- <5% plasma cells in bone marrow
Very Good Partial Response (VGPR) 1:
- Serum and urine M-protein detectable by immunofixation but not on electrophoresis OR
- ≥90% reduction in serum M-protein plus urine M-protein <100 mg/24h
Partial Response (PR) 1:
- ≥50% reduction of serum M-protein
- ≥90% reduction in 24h urinary light chain excretion or to <200 mg/24h
Clinical Pearls and Pitfalls
- Serum FLC assay cannot completely replace 24-hour UPEP for monitoring patients with measurable urinary M-protein 1
- FLC measurements can be affected by renal function, potentially leading to false elevations 1, 4
- After quantifying the involved light chain, it's crucial to use the same test for serial measurements to ensure accurate relative quantification 1
- Urine immunofixation may become negative earlier than serum FLC ratio normalization during treatment response 4
- Increased urinary monoclonal protein excretion (≥200 mg/24h) in patients with FLC ratio ≥100 indicates higher risk of progression 3
- Light chain myeloma typically has a more aggressive course and poorer prognosis than intact immunoglobulin myeloma 2
- FLC measurements show faster changes in response to treatment due to shorter serum half-life (2-6 hours) compared to intact immunoglobulins (21 days for IgG) 5, 6