Assessment of the Performance of Serum Heavy Chains Immunoassay to Monitor Response to Treatment and Its Correlation with Other Tumor Measurements In Serial Samples From Patients with Newly Diagnosed MM
Authors: Suvannasankha Attaya , Farag Sherif , Harding Stephen , Durie Brian GM , Abonour Rafat 
Published: October 2019

Abstract
Abstract 2986
Currently available methods for the measurement of tumor load in multiple myeloma include the measurement of monoclonal proteins by electrophoresis, the percentage of myeloma cells in the bone marrow, and the more recently described serum free light chain (FLC) assay. The recent development of antibodies which bind to conformational epitopes spanning the junctional regions between the bound or light chains and their respective heavy chains has now allowed for the specific measurement of serum IgGκ, IgGλ, IgAκ and IgAλ concentrations (HLC). How this novel test may fit in with the other tumor measuring methods has not been fully established. We evaluated the correlation of serum HLC assays with FLC assays, serum monoclonal protein measurement by electrophoresis (M spike), and total immunoglobulin G or A, in serial samples of patients with newly diagnosed MM undergoing a lenalidomide containing induction regimen.

Methods:
Total immunoglobulins were quantitated by immunonephelometry. HLC and FLC concentrations were quantitated with standard reagents (The Binding Site, Ltd). M spike was evaluated by electrophoresis. Pearson's regression was used to determine correlations among the above tests.

Result:
Serum samples at baseline, 3 months and 6 months after therapy from 16 patients were assayed. Ig subtypes are as follows: 7 IgGκ, 1 IgGλ, 3 IgAκ, 3 IgAλ, 1 light chain and 1 nonsecretory myeloma. The FLC of the involved chain was abnormal in all but one case, including cases of light chain and nonsecretory MM. The HLC of the involved chain was abnormal in all cases, except the patient with non-secretory MM, in which case, the IgG and were both suppressed. HLC did not correlate well with FLC (r=0.08). Similarly, the HLC k/l ratio did not correlate well with FLC k/l ratio (r=0.33). The HLC moderately correlated with M spike (r= 0.49). The HLC of the involved chain correlate strongly to total immunoglobulin (r=0.9).
At 3 months post treatment, HLC and FLC of the involved chains decreased dramatically from baseline levels and plateaud in most cases. HLC kinetics seemed to be slower than FLC as, in 4 cases, FLC normalized before HLC. Interestingly, in these 4 cases, the continual decline in HLC correlated better to the change in the M spike. We also observed a recovery of the previously suppressed uninvolved HLC in 6 cases, leading to the continual improvement in the HLC κ/λ ratio even after the HLC normalization.

Conclusion:
HLC kinetics showed differences compared to FLC and correlated better with the monoclonal spike. FLC normalized faster but, once normalized, seemed to correlate less well than HLC with M spike and ongoing clinical response. Increased HLC of the uninvolved chain was observed in a subset of patients, after therapy. The HLC κ/λ ratio, which takes into account the changes of the uninvolved chain, is an appealing tool for disease monitoring once HLC of the involved chain normalized. HLC is complimentary to other tumor assessment tools and needs to be further explored in a larger patient cohort.

Disclosures:
No relevant conflicts of interest to declare.