Chapter 8

A number of studies have compared N Latex FLC and Freelite for monitoring MM [982][981][984][985]. Many report that whilst the two assays show a similar trend in results, differences in absolute values may lead to significant discrepancies in clinical interpretation. For example Lutteri et al. [982] report a case of λ LCMM in which progressive disease was confirmed by Freelite before N Latex FLC (Figure 8.11.).

Popat et al. [984] compared Freelite and N Latex FLC assays to monitor 59 MM patients treated with Bortezomib-based regimens. The proportion of patients who had measurable disease was much higher by Freelite than by N Latex FLC assays (64% vs. 37%, n=59), and for the subgroup of patients with measurable disease by both assays (n=20), the agreement in responses assigned using the two tests was only moderate (Weighted Kappa = 0.54). Similar results have been reported by others [983]. Popat et al. [984] reported that during follow-up, Freelite identified clonal disease in 4/61 MM patients when the N Latex FLC ratio had normalised. In each case, clonal disease was confirmed by the presence of a monoclonal protein on serum IFE suggesting that the N Latex FLC assays may lack sensitivity to detect residual disease. Similar results were reported by others [985].

Heaney et al. [980] compared the ability of Freelite and Seralite-FLC to monitor 132 LCMM patients. At presentation, absolute dFLC levels were higher on Freelite than Seralite-FLC (median values: 3207.8 mg/L vs. 657.5mg/L), but at maximum response a similar percentage reduction in dFLC was observed. However, the authors noted a significant difference in assigned response categories: fewer patients achieved a complete response (defined as normalisation of the sFLC ratio) by Freelite (41.7%) than by Seralite-FLC (52.3%). This may reflect insensitivity of the lateral flow-based assay. At disease relapse, the increase in dFLC by Freelite was consistently higher than the increase by Seralite-FLC (median values: 558 mg/L vs. 101.2 mg/L), and the authors proposed a Seralite-FLC cut-off value to define progressive disease (>30 mg/L). This is much lower than the definition in IMWG guidelines, which are based on Freelite values (25% increase in dFLC, provided the absolute increase iFLC >100 mg/L, see Sections 8.7 and 25.3).

Jacobs et al. [1178] compared Freelite and Sebia FLC assays to monitor four patients with LCMM. Both assays showed a parallel trend in results at all sampling points, but there were substantial differences in the absolute values reported by both FLC assays.

In summary, quantitative differences between polyclonal and monoclonal antibody-based FLC assays may lead to significant differences in clinical interpretations when assessing response to treatment and disease relapse [201][985][983]. For this reason, the different FLC assays should not be used interchangeably, nor should it be assumed that international guidelines developed with Freelite assays can be applied to N Latex FLC or Seralite-FLC.