Original Article
IgA Kappa/IgA Lambda Heavy/Light Chain Assessment in the Management of Patients With IgA Myeloma phanie Guidez, MD1; Sarah Bonnet, MD1; Helene Demarquette, MD1; Eileen M. Boyle, MD1; Guillemette Fouquet, MD1; Ste 1 1 Remy Dulery, MD ; Charles Herbaux, MD ; Marie Pierre Noel, MD1; Salomon Manier, MD1; Suzanna Schraen, PharmD, PhD2; 2; Bernadette Hennache, PharmD2; Marie Odile Petillon, MD1; Brigitte Onraed, PharmD2; Jean-Luc Faucompre 3 Claire Mathiot, MD ; Herve Avet-Loiseau, MD, PhD4; Thierry Facon, MD1; Stephen J. Harding, PhD5; Philippe Moreau, MD, PhD6; and Xavier Leleu, MD, PhD1
BACKGROUND: Accurate quantification of immunoglobulin A (IgA) monoclonal immunoglobulins by serum protein electrophoresis (SPEP) can be difficult and can impact the assessment of response among patients with multiple myeloma (MM). Therefore, there is a need to identify new assays that better reflect disease burden and response to treatment, and correlate with patient outcome. IgA Hevylite (HLC) measures IgA kappa and IgA lambda separately and provides precise quantitative measurements of the monoclonal IgA expression and polyclonal-isotype matched suppression. In the current study, the authors assessed the usefulness of these assays in the diagnosis of IgA MM and sought to comment on the prognostic value of the assays. METHODS: A study of 157 patients with IgA MM for whom diagnostic samples were available was performed. HLC measurements were performed on a nephelometer and the results were compared with those of electrophoresis. RESULTS: All presentation sera (100 IgA kappa specimens and 57 IgA lambda specimens) were found to have abnormal IgA HLC ratios (IgA kappa median ratio: 336.2 [range, 8.2-7353] and IgA lambda ratio: 0.011 [range, 0.0003-0.45]). In comparison, SPEP bands were quantifiable in only 105 of 157 samples (67%) (median, 28.5 g/L [range, 2.2 g/L-98 g/L]). Of the total of 157 patients, 12 patients (8%) presented with oligosecretory myeloma (4 g/L), however, 1 patient with IgA lambda MM with an abnormal HLC ratio had a normal total IgA level (1.3 g/ L) (Table 2). All 5 patients (3 with IgA kappa MM and 2 with IgA lambda MM) whose M-spikes migrated into both the beta and gamma regions had accurately quantifiable SPEP bands and abnormal HLC ratios (data not shown). Cancer
December 15, 2014
IgA Hevylite Test/Boyle et al
TABLE 3. HLC and Total IgA Measurements in Samples With Unspecified Migration Patternsa Unspecified Migration Patterns Patients With IgA Patients With IgA Kappa MM Lambda MM No. of patients Median total IgA (range), g/L Median IgA kappa (range), g/L Median IgA lambda (range), g/L Median IgA HCL ratio (range)
5 15.5 (11-42.1) 10 (8.4-67.4) 0.25 (0.02-0.89) 82.2 (9.5-748)
15.6 0.33 9.5 0.03
6 (8.3-27) (0.02-0.66) (7.7-40.9) (0.003-0.035)
Abbreviations: HLC, Hevylite chain test; IgA, immunoglobulin A; MM, multiple myeloma. a Samples were subcategorized using isotype.
Table 3 summarizes the total IgA and HLC results for 11 patients with unspecified SPEP migration patterns. All 11 patients (5 with IgA kappa MM and 6 with IgA lambda MM) had no reported SPEP results, but had abnormal total IgA levels and abnormal HLC ratios. Patients With Oligosecretory MM
Table 2 summarizes the SPEP, Bence-Jones proteinuria, serum-free light chain, and total IgA and IgA HLC measurements for 12 of 157 patients (8%) (3 with IgA kappa MM and 9 with IgA lambda MM) with oligosecretory MM (
IgA Kappa/IgA Lambda Heavy/Light Chain Assessment in the Management of Patients With IgA Myeloma phanie Guidez, MD1; Sarah Bonnet, MD1; Helene Demarquette, MD1; Eileen M. Boyle, MD1; Guillemette Fouquet, MD1; Ste 1 1 Remy Dulery, MD ; Charles Herbaux, MD ; Marie Pierre Noel, MD1; Salomon Manier, MD1; Suzanna Schraen, PharmD, PhD2; 2; Bernadette Hennache, PharmD2; Marie Odile Petillon, MD1; Brigitte Onraed, PharmD2; Jean-Luc Faucompre 3 Claire Mathiot, MD ; Herve Avet-Loiseau, MD, PhD4; Thierry Facon, MD1; Stephen J. Harding, PhD5; Philippe Moreau, MD, PhD6; and Xavier Leleu, MD, PhD1
BACKGROUND: Accurate quantification of immunoglobulin A (IgA) monoclonal immunoglobulins by serum protein electrophoresis (SPEP) can be difficult and can impact the assessment of response among patients with multiple myeloma (MM). Therefore, there is a need to identify new assays that better reflect disease burden and response to treatment, and correlate with patient outcome. IgA Hevylite (HLC) measures IgA kappa and IgA lambda separately and provides precise quantitative measurements of the monoclonal IgA expression and polyclonal-isotype matched suppression. In the current study, the authors assessed the usefulness of these assays in the diagnosis of IgA MM and sought to comment on the prognostic value of the assays. METHODS: A study of 157 patients with IgA MM for whom diagnostic samples were available was performed. HLC measurements were performed on a nephelometer and the results were compared with those of electrophoresis. RESULTS: All presentation sera (100 IgA kappa specimens and 57 IgA lambda specimens) were found to have abnormal IgA HLC ratios (IgA kappa median ratio: 336.2 [range, 8.2-7353] and IgA lambda ratio: 0.011 [range, 0.0003-0.45]). In comparison, SPEP bands were quantifiable in only 105 of 157 samples (67%) (median, 28.5 g/L [range, 2.2 g/L-98 g/L]). Of the total of 157 patients, 12 patients (8%) presented with oligosecretory myeloma (4 g/L), however, 1 patient with IgA lambda MM with an abnormal HLC ratio had a normal total IgA level (1.3 g/ L) (Table 2). All 5 patients (3 with IgA kappa MM and 2 with IgA lambda MM) whose M-spikes migrated into both the beta and gamma regions had accurately quantifiable SPEP bands and abnormal HLC ratios (data not shown). Cancer
December 15, 2014
IgA Hevylite Test/Boyle et al
TABLE 3. HLC and Total IgA Measurements in Samples With Unspecified Migration Patternsa Unspecified Migration Patterns Patients With IgA Patients With IgA Kappa MM Lambda MM No. of patients Median total IgA (range), g/L Median IgA kappa (range), g/L Median IgA lambda (range), g/L Median IgA HCL ratio (range)
5 15.5 (11-42.1) 10 (8.4-67.4) 0.25 (0.02-0.89) 82.2 (9.5-748)
15.6 0.33 9.5 0.03
6 (8.3-27) (0.02-0.66) (7.7-40.9) (0.003-0.035)
Abbreviations: HLC, Hevylite chain test; IgA, immunoglobulin A; MM, multiple myeloma. a Samples were subcategorized using isotype.
Table 3 summarizes the total IgA and HLC results for 11 patients with unspecified SPEP migration patterns. All 11 patients (5 with IgA kappa MM and 6 with IgA lambda MM) had no reported SPEP results, but had abnormal total IgA levels and abnormal HLC ratios. Patients With Oligosecretory MM
Table 2 summarizes the SPEP, Bence-Jones proteinuria, serum-free light chain, and total IgA and IgA HLC measurements for 12 of 157 patients (8%) (3 with IgA kappa MM and 9 with IgA lambda MM) with oligosecretory MM (
