What are the criteria for IMWG (International Myeloma Working Group) response assessment in light chain myeloma?

IMWG Response Assessment Criteria for Light Chain Multiple Myeloma

For light chain multiple myeloma, response assessment should be based primarily on serum free light chain (FLC) measurements, with 24-hour urine collections serving as a complementary method when appropriate. 1, 2, 3

Measurable Disease Criteria

• Light chain multiple myeloma is considered measurable when the involved serum FLC level is ≥10 mg/dL and the FLC ratio is abnormal 4, 1
• All measurable parameters should be followed, with particular emphasis on serum FLC measurements for light chain myeloma 4, 1
• 24-hour urine collections for total protein and urine protein electrophoresis remain important complementary assessments but may lack sensitivity at low monoclonal protein levels 2, 3

Response Categories for Light Chain Myeloma

Stringent Complete Response (sCR)

• Complete response criteria (see below) plus normal FLC ratio (0.26-1.65) and absence of clonal plasma cells in bone marrow by immunohistochemistry or flow cytometry 4, 1
• Laboratory-specific reference ranges for FLC ratio may be used when different from 0.26-1.65 4

Complete Response (CR)

• Negative immunofixation on serum and urine
• Disappearance of any soft tissue plasmacytomas
• <5% plasma cells in bone marrow aspirate 4, 1
• For patients whose only measurable disease is by serum FLC: CR requires negative serum and urine immunofixation plus normal FLC ratio on two consecutive assessments 4

Very Good Partial Response (VGPR)

• 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 4
• For patients whose only measurable disease is by serum FLC: VGPR requires >90% decrease in the difference between involved and uninvolved FLC levels on two consecutive assessments 4

Partial Response (PR)

• ≥50% reduction in serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24h 4
• For patients whose only measurable disease is by serum FLC: PR requires ≥50% decrease in the difference between involved and uninvolved FLC levels 4, 1
• If serum and urine M-protein are unmeasurable, and serum FLC assay is also unmeasurable, ≥50% reduction in bone marrow plasma cells is required (provided baseline percentage was ≥30%) 4

Minimal Response (MR)

• ≥25% but <50% reduction of serum M-protein and reduction in 24-hour urine M-protein by 50-89% 4

Stable Disease (SD)

• Not meeting criteria for CR, VGPR, PR, MR, or progressive disease 4
• Not recommended for use as an indicator of response; stability is best described by providing time-to-progression estimates 4

Progressive Disease (PD)

For patients whose only measurable disease is by serum FLC:

• ≥25% increase from lowest response value in the difference between involved and uninvolved FLC levels (absolute increase must be >10 mg/dL) 4
• If serum FLC is also not measurable: ≥25% increase in bone marrow plasma cells (absolute percentage must be ≥10%) 4

Practical Implementation

• Response assessments should be performed after one cycle of therapy, then every other cycle once a response trend is observed, and less frequently once the patient reaches plateau phase 4
• All responses (except for bone marrow and imaging assessments) should be confirmed with a second measurement 4
• Confirmatory testing can be done on the same day from a separate blood draw or urine collection done a day apart 4
• Serum FLC ratio normalization is an independent prognostic factor for extended progression-free survival and overall survival 5
• When using serum FLC for monitoring, it's crucial to use the same test for serial measurements to ensure accurate relative quantification 1

Important Considerations

• Approximately 48-50% of patients with multiple myeloma have evaluable disease by serum FLC criteria (involved FLC ≥10 mg/dL), limiting its utility in some patients 6
• Serum FLC measurements may be affected by renal function, potentially leading to false elevations 1
• Minimal residual disease (MRD) assessment by next-generation flow cytometry or sequencing provides deeper response evaluation beyond conventional complete response 7
• PET/CT imaging can complement serum and urine assessments, particularly for evaluating extramedullary disease 4
• Light chain escape (increasing FLC levels without corresponding changes in intact immunoglobulin) can occur during disease progression and should be monitored 5

By consistently applying these standardized response criteria, clinicians can accurately compare results across clinical trials and evaluate the effectiveness of different therapies in individual patients 4.