Correlation Among Different Plasma Cell Disorders Markers and Immunoglobulin Heavy Light Chains (HLC)

Heavy light chain (HLC) assays allow for accurate quantification of involved and uninvolved immunoglobulins (Ig) of the affected isotype. HLC ratio is of particular interest in measuring low level disease where there is limited utility for serum protein electrophoresis (SPEP) to measure the low M-spike and challenging to quantify. Serum immunofixation (SIFx), being a non-quantitative test cannot accurately define the amount of disease. Limited data exists to understand the utility of HLC testing, hence we tried to study the correlation of this test to some of the established plasma cell disorder markers: serum free light chains (SFLC), SPEP (M-spike) and involved total Ig levels.

A total of 1098 samples from 480 patients with IgG [315 IgG Kappa (k) and 165 IgG Lambda (l)] plasma cell disorders (multiple myeloma, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma and plasmacytoma) and 329 samples from 160 IgA (98 IgAk patients and 60 IgAl) plasma cell disorder patients were included in analysis. Correlation was determined between HLC levels, HLC ratio and SFLC levels for all patients. Correlation was determined for each isotype separately using non parametric Spearman Correlation co-efficient (SCC).

In IgA patients, there is strong correlation between HLC levels (IgAk and IgAl) and M-spike (0.85; p<0.0001 and 0.82; p<0.0001, respectively) as well as involved Ig (0.99; p<0.0001; 0.99; p<0.0001, respectively). Similar strong correlation was seen between HLC ratios and M-spike and involved Ig. In IgG patients, there is strong correlation, but smaller than IgA, between HLC levels (IgGk and IgGl) and M-spike (0.72; p<0.0001 and 0.75; p<0.0001, respectively) as well as involved Ig (0.91; p<0.0001; 0.78; p<0.0001, respectively). Similar correlation was seen between HLC ratios and M-spike and involved Ig. We also observed a strong correlation of FLCk with IgAk (0.65; p<0.0001) as well as of FLCl with IgA l too (0.69; p<0.0001). Similarly, FLCk with IgGk (0.56; p<0.0001) and FLCl with IgG l (0.69; p<0.0001) exhibited strong correlation.

The presence of strong correlation between M-spike quantification, serum free light chains, as well as total involved immunoglobulins in the largest sample size reported to date, suggests the feasibility of detection of isotype bands with HLC antibodies and its potential role for clinical utility in disease staging and monitoring. Prognostic usefulness of this testing in identifying residual disease and its correlation with survival in myeloma patients will be presented at the meeting.

Kaufman:Onyx: Consultancy; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Janssen: Consultancy; Millenium: Consultancy; Merck: Research Funding. Boise:Onyx Pharmaceuticals: Consultancy. Lonial:Millennium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; BMS: Consultancy; Sanofi: Consultancy; Onyx: Consultancy.