Hevylite assays allow the measurement of isotype-specific suppression of the uninvolved HLC-pair (i.e. suppression of IgGλ in an IgGκ patient) (Section 11.2). As HLC-pair suppression has been identified as an adverse prognostic marker in MM and MGUS patients (Chapters 13 and 20), it may also have prognostic significance in SMM. In the largest prospective study of HLC and SMM published to date, HLC-pair suppression was observed in 39/50 (78%) patients at diagnosis, compared with 32/50 (64%) patients who had conventional immunoparesis, i.e. suppression of uninvolved polyclonal immunoglobulins . Of the 18 patients without immunoparesis, HLC-pair suppression was present in 8/18 cases and was associated with adverse biological features such as more skewed κ/λ sFLC ratios and a more pronounced distribution of abnormal/normal plasma cells. Isola et al.  prospectively monitored 18 patients with SMM. Highly abnormal HLC ratios (<0.02 or >45) and severe HLC suppression (>50% below lower level of normal) were found in 44% (8/18) and 55% (10/18) patients at diagnosis, and both features were present in all three patients who progressed to symptomatic disease during follow-up.
In an initial investigation by Maisnar et al. , HLC-pair suppression was associated with increased risk of progression in IgG (n=51, p=0.006) but not IgA (n=20) SMM, although patient numbers were small. Further studies are now required to confirm the prognostic significance of HLC-pair suppression in SMM.