Assessment of Heavy/ Light Chain Pairs of Immunoglobulin (Hevylite™ assay) – Benefit for Stratification of Multiple Myeloma?

Abstract

The aim of the study was the comparison of two novel stratification models in multiple myeloma (MM), ie. according to Avet- Loiseau (A L) and according to Ludwig (L), based on the HLC r index (ratio of serum levels of involved- HLC/ uninvolved HLC, ie. HLC κ/ HLC λ assessed using ie. nephelometric/turbidimetric technique using specific polyclonal antibodies on a Binding Site SPA(PLUS)) technique) and β(2) microglobulin (β(2) M) with selected prognostic factors (PF) of MM and staging systems according to Durie- Salmon (D S) and International Staging System (ISS). In a cohort of 132 patients (94 with IgG and 38 with IgA type of MM) at the time of dia-gnosis, we assessed HLC r, select-ed PF and D S, ISS, A L and L stratification systems. Unlike in IgA isotype, in IgG isotype we found a significant relationship of HLC r to stratification according to D S and ISS with the difference between A and B substages according to D S (p = 0.049) and between ISS stages 1 vs. 3 (p = 0.001). In the IgG group, there was highly significant relationship of the depth of Hb and albumin decrease and β(2) M increase to the results of stratification according to ISS, A L and L model (p < 0.0001), increase of LDH in the ISS system and A L, and creatinine according to ISS and L but not the relationship of the stages according to any of the stratification systems to the values of FLC r (ratio of serum free light chains κ/ λ of immunoglobulin), thrombocytes and Ca. In the IgA type, there was a significant relationship of the depth of the decrease of Hb, thrombocytes, albumin and increase of β(2) M to the results of stratification according to ISS, A L and L and increase of creatinine in the case of ISS, but not of the values of FLC r, Ca and LDH in the case of any of the stratification systems. The degree of correlation of selected PF, especially of Hb, albumin and β(2) M, event. of thrombocytes, LDH and creatinine to the stages according to ISS and to stage 1-3 according to A L and L model was in IgG vs IgA isotype significantly different (p < 0.0001- 0.030). Staging system according to ISS had proportional distribution of stages 1- 3, whereas in the A L model prevailed in IgA and IgG isotype risk category 2, ie. intermediate-risk (47.3 and 44.7%) and in the L model prevailed risk category 3, ie. high-risk (41.5 and 52.6%) with low count of category 1, ie. low- risk category (23.4 and 10.5%). McNemar- Bowker test of symmetry showed in both types of MM the highest concordance between the stratification according to D S and L in category 3, ie. high-risk (31.9 vs. 28.9%) with overall accord only in 53.2 and 42.1% and with significant shift in the case of IgG isotype only (p = 0.036). In IgG and IgA isotype there was an overall concordance in the distribution of categories 1- 3 according to ISS vs. A L (62.4 and 63.2%) but with significant shift of the stratification (p = 0.002 and 0.028). In the case of IgG and IgA isotype there was a close relationship between the models A L and L (64.5 and 81.6%) with significant stratification shift (p < 0.0001 and 0.030). The new stratification models for MM according to A L and L are easily practically applicable, with close relationship to principal PF but they need separate assessment of IgG and IgA isotypes of MM. The choice of optimal model for routine practice needs a validation study aimed at progression free survival and overall survival.