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THE SERUM HEAVY/LIGHT CHAIN IMMUNOASSAY SERVES AS AN ADDITIONAL VALUABLE TOOL FOR SENSITIVE PARAPROTEIN ASSESSMENT, RISK STRATIFICATION AND DISEASE MONITORING IN PATIENTS WITH MONOCLONAL GAMMOPATHY
Author(s): ,
Christine Greil
Affiliations:
University hospital Freiburg,Freiburg,Germany
,
Felix Gaiser
Affiliations:
University hospital Freiburg,Freiburg,Germany
,
Gabriele Ihorst
Affiliations:
University hospital Freiburg,Freiburg,Germany
,
Emmanuel Bisse
Affiliations:
University hospital Freiburg,Freiburg,Germany
,
Ralph Wäsch
Affiliations:
University hospital Freiburg,Freiburg,Germany
Monika Engelhardt
Affiliations:
University hospital Freiburg,Freiburg,Germany
(Abstract release date: 05/19/16) EHA Library. Greil C. 06/09/16; 132851; E1302
Dr. Christine Greil
Dr. Christine Greil
Contributions
Abstract
Abstract: E1302

Type: Eposter Presentation

Background
A novel polyclonal immunoassay specific for the different light chain types of intact immunoglobulins (Ig) enables measurement of changes in the production of clone specific Ig and of the non-involved polyclonal Ig of the same isotype. This serum heavy/light chain immunoassay (HLC) was developed to recognize and separately quantify light chain types of each intact Ig class. Prior studies have demonstrated that immunofixation (IFE) and HLC-assay are complementary methods, and that HLC-values and -ratios serve as additional parameters for evaluation of response and early relapse recognition in patients with monoclonal gammopathies.

Aims
We aimed to a) investigate the HLC-assay compared to standard Multiple Myeloma (MM)-diagnostics in consecutive MM, smoldering MM (SMM) and Monoclonal gammopathy of undetermined significance (MGUS) patients, b) assess HLC results in MM vs. MGUS and SMM patients, c) define a possible HLC cut-off for high-risk SMM patients and d) decipher the role of the HLC-assay for response, stage groups, progression free (PFS) and overall survival (OS) in MM.

Methods
We investigated the HLC [Hevylite™]-assay and compared its results to standard diagnostics, such as the capillary zone electrophoresis (CZE) and serum free light chain (SFLC)-assay: SFLC and HLC (IgGκ/IgGλ, IgAκ/IgAλ, IgMκ/IgMλ) measurements were performed using polyclonal antisera FreeliteTM and Hevylite™ assays. Standard diagnostics for MGUS, MM and Waldenström's Macroglobulinemia (WM) patients also included IFE and bone marrow aspiration/biopsies as well as stage (Durie and Salmon and International Staging System [ISS]) and EBMT response assessment.

Results
We assessed 146 consecutive patients with abnormal M-spike via CZE: 57 had IgGκ-MM, 24 IgGλ-MM, 8 IgAκ-MM, 7 IgAλ-MM, 5 SMM, 5 light-chain-only MM, 28 MGUS and 12 had IgM WM. HLC-values and -ratios significantly correlated with the respective Ig values, isotype-matched SFLCs, M-gradient, ISS and remission status. Of note, with measurement of HLCs, up to 33% more pathological serum values were detected than via SFLC-assay alone. Moreover, due to pathological HLC-values, 57% of patients with MGUS were reclassified as SMM or MM, suggesting that the assay may assist in recognition of true MGUS, SMM vs. symptomatic MM patients. Furthermore, patients with WM-M-spikes - the latter often difficult to quantify - revealed a clearly abnormal median IgMκ/λ ratio of 231 (normal range: 1.0-2.4). PFS in patients with extreme (<0.5/>50) HLC-values vs. those without (0.5-50) was significantly impaired.

Conclusion
The HLC-assay is of particular value to monitor slow or indolent disease progression. Moreover, in WM, it can be a helpful additional technique to quantify the amount of monoclonal Ig clone and to more reliably decipher MGUS from SMM/MM patients.

Session topic: E-poster
Abstract: E1302

Type: Eposter Presentation

Background
A novel polyclonal immunoassay specific for the different light chain types of intact immunoglobulins (Ig) enables measurement of changes in the production of clone specific Ig and of the non-involved polyclonal Ig of the same isotype. This serum heavy/light chain immunoassay (HLC) was developed to recognize and separately quantify light chain types of each intact Ig class. Prior studies have demonstrated that immunofixation (IFE) and HLC-assay are complementary methods, and that HLC-values and -ratios serve as additional parameters for evaluation of response and early relapse recognition in patients with monoclonal gammopathies.

Aims
We aimed to a) investigate the HLC-assay compared to standard Multiple Myeloma (MM)-diagnostics in consecutive MM, smoldering MM (SMM) and Monoclonal gammopathy of undetermined significance (MGUS) patients, b) assess HLC results in MM vs. MGUS and SMM patients, c) define a possible HLC cut-off for high-risk SMM patients and d) decipher the role of the HLC-assay for response, stage groups, progression free (PFS) and overall survival (OS) in MM.

Methods
We investigated the HLC [Hevylite™]-assay and compared its results to standard diagnostics, such as the capillary zone electrophoresis (CZE) and serum free light chain (SFLC)-assay: SFLC and HLC (IgGκ/IgGλ, IgAκ/IgAλ, IgMκ/IgMλ) measurements were performed using polyclonal antisera FreeliteTM and Hevylite™ assays. Standard diagnostics for MGUS, MM and Waldenström's Macroglobulinemia (WM) patients also included IFE and bone marrow aspiration/biopsies as well as stage (Durie and Salmon and International Staging System [ISS]) and EBMT response assessment.

Results
We assessed 146 consecutive patients with abnormal M-spike via CZE: 57 had IgGκ-MM, 24 IgGλ-MM, 8 IgAκ-MM, 7 IgAλ-MM, 5 SMM, 5 light-chain-only MM, 28 MGUS and 12 had IgM WM. HLC-values and -ratios significantly correlated with the respective Ig values, isotype-matched SFLCs, M-gradient, ISS and remission status. Of note, with measurement of HLCs, up to 33% more pathological serum values were detected than via SFLC-assay alone. Moreover, due to pathological HLC-values, 57% of patients with MGUS were reclassified as SMM or MM, suggesting that the assay may assist in recognition of true MGUS, SMM vs. symptomatic MM patients. Furthermore, patients with WM-M-spikes - the latter often difficult to quantify - revealed a clearly abnormal median IgMκ/λ ratio of 231 (normal range: 1.0-2.4). PFS in patients with extreme (<0.5/>50) HLC-values vs. those without (0.5-50) was significantly impaired.

Conclusion
The HLC-assay is of particular value to monitor slow or indolent disease progression. Moreover, in WM, it can be a helpful additional technique to quantify the amount of monoclonal Ig clone and to more reliably decipher MGUS from SMM/MM patients.

Session topic: E-poster

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