Intact Immunoglobulin Multiple Myeloma (IIMM)

96% of IIMM patients have abnormal light chain concentrations or kappa/lambda ratio

Some 82% of patients with Multiple Myeloma produce a detectable monoclonal protein of intact immunoglobulin heavy chain type G, A, M, D or E and either light chain kappa or lambda. This paraprotein can be used as a serum marker for diagnosis and levels can be monitored during treatment to assess efficacy.

Measurement of serum free light chains with Freelite has shown that 96% of patients with Intact Immunoglobulin Multiple Myeloma also have abnormal light chain concentration or abnormal kappa/lambda (κ/λ) ratios in addition to the intact immunoglobulin.1

 

Graph 5

Concentrations of serum free light chains in 314 patients with IgG Myeloma compared with 282 normal sera.

Graph 6

Concentrations of serum free light chains in 142 IgA, 36 IgD and 5 IgE Myeloma patients compared with 282 normal sera.

Image 1

Monitoring of one of the 17 Myeloma patients using IgGκ and free κ. Electrophoresis gels are shown for each sample. CVAMP = cyclophosphamide, vincristine, adriamycin, melphalan, prednisolone: HDM: high dose melphalan and stem cell transplant.1

Serial samples from 17 IIMM patients were also studied1.

"Reductions in the concentrations of the intact immunoglobulins and the FLC occurred in parallel in all patients. The extent of change in the FLC concentrations was, however, greater than that of the total intact immunoglobulin in all but one patient. The range of FLC reduction was 2.1-1678-fold (mean 219-fold) whereas the range of total, intact immunoglobulin reduction was 1.5-88-fold (mean 14.6-fold)."

FLC readily pass through the glomeruli, with a serum half-life of 2-6 hours. In contrast the serum half-life of intact immunoglobulin IgG is 20-25d.

Another study2 analysed the changes in serum FLC after autologous peripheral blood stem cell transplantation (PBSCT) in 19 patients.

"The half-life of serum FLC adds only a few hours to the true picture of the tumor killing rate. The rate of fall and range of reduction of FLC varied between individual patients indicating different tumor killing rates and chemosensitivity. By contrast, the concentrations of total and monoclonal immunoglobulin were continuing to fall even after leaving hospital, reflecting the long half-life of serum immunoglobulins."

Serum FLC measurement showed a good degree of correlation with bone marrow assessments of myeloma.3

 
Bone Marrow
 
Normal
Abnormal
Serum Free Light Chains
Normal
22
7
 
Abnormal
10
66
 
Urine Free Light Chains
Normal
25
31
 
Abnormal
7
42
 
Serum Immunofixation
Normal
14
6
 
Abnormal
18
67

 

Results of the comparison between serum free light chains, urine free light chains, serum immunofixation and bone marrow assessment. The number of patients who had abnormal bone marrows but normal urine FLC illustrates the increased sensitivity of serum FLC measurements.

 

Summary

References

  1. G. P. Mead, H. D. Carr-Smith, M. T. Drayson, G. J. Morgan, J. A. Child and A. R. Bradwell.
    "Serum free light chains for monitoring multiple myeloma"
    BJH 2004;126:348-354

    Reference: MKG228 Quantity:

  2. Guy Pratt, Graham P Mead, Keith R Godfrey et al.
    "The tumor kinetics of multiple myeloma following autologous stem cell transplantation as assessed by measuring serum-free light chains"
    Leukemia & Lymphoma, January 2006; 47(1): 21 - 28

    Reference: MKG296 Quantity:

  3. GP Mead, S Reid, B Augustson, MT Drayson, AR Bradwell, JA Child
    Comparison of serum and urine free light chain measurements with bone marrow assessments in multiple myeloma
    haematologica / the hematology journal 2005;90(s1):108(PO.407)