Research has indicated that HLC analysis can provide prognostic information when performed early in a treatment regimen, at the end of consolidation therapy (Section 18.4) or at the time of maximum response. From a study of 44 MM patients treated with carfilzomib, lenalidomide and dexamethasone, Bhutani et al.  reported that normalisation of the HLC ratio after 2 cycles of therapy was significantly associated with achieving a sCR (p=0.001). In a multivariate model that initially included monoclonal immunoglobulin, dFLC, normalised sFLC ratio, difference between involved and uninvolved HLC concentration (dHLC) and normalised HLC ratio; only dHLC (<2.6 g/L vs. ≥2.6 g/L) remained as an independent factor after 2 treatment cycles. A preliminary analysis of 70 patients treated with bortezomib  suggested that the HLC ratio was a more sensitive monitoring tool than the monoclonal immunoglobulin and suppression of the uninvolved HLC isotype (HLC pair suppression) was associated with poor PFS and OS.
Scheid et al.  studied the prognostic value of HLC measurements 6 months post-induction in 292 transplant-eligible MM patients (212 IgG, 86 IgA). Patients who achieved a HLC-CR (defined as a normal HLC ratio) had a superior OS compared to those who achieved lesser degrees of HLC response (86.5% vs. 71.4% at 60 months, p=0.039). D’Souza confirmed the prognostic value of a HLC-CR in patients who had not achieved a VGPR or better, prior to transplant .
Fouquet et al.  compared the reduction in HLC pair suppression with the depth of response in 107 IIMM patients following treatment with pomalidomide and dexamethasone. For patients achieving a VGPR or better, 75% had improved levels of the uninvolved HLC pair (defined as a 50% increase from the time of maximum response), compared to 31% and 13% for patients achieving a PR or SD, respectively (p=0.005). Therefore, recovery of the uninvolved HLC pair correlates with depth of response. Similar findings were reported by Harutyunyan et al.  and Michallet et al. . Harutyunyan et al.  also demonstrated that MM patients with an uninvolved HLC concentration within the normal range showed a longer PFS than those with concentrations below the normal range (45 months vs. 11 months, p=0.0019). Similar results have been published by others .
Ludwig et al.  examined HLC pair suppression of patients at best response. They observed that HLC pair suppression of >50% at best response correlated significantly with subsequent survival (49.0 vs 71.9 months, HR: 1.581, p=0.035). Expanding on these results, Michallet et al.  reported that HLC pair suppression of >50% remains prognostic of PFS in patients who achieve a CR.