Apart from the practical advantages of using serum samples rather than urine, the principal advantages of monitoring patients with serum tests derives from their greater clinical sensitivity and prognostic utility. The main studies are reported in detail in the relevant chapters, listed in Section 24.6, and monitoring examples are shown in Figure 24.1 and Section 15.2.. After treatment, 32% of patients achieved complete remission (CR) according to their urine results while only 11% achieved normalisation of their sFLC ratios; a percentage closely aligned to the 9.8% CR rate seen in patients monitored by their monoclonal intact immunoglobulin (and receiving the same treatment). Similar results have now been reported in a number of studies by the French IFM group .  compared sFLC and urine electrophoresis measurements for monitoring 157 IIMM and 25 LCMM patients. At each time point, the κ/λ sFLC ratio was more sensitive than uIFE for the detection of monoclonal FLCs and showed a better correlation with sIFE results (Figure 24.6). A separate analysis of 111 LCMM enrolled into the IFM-2009 trial  concluded that in keeping with previous reports, sFLC analysis was a more sensitive indicator of disease than urinalysis. The study also demonstrated that normalisation of sFLC parameters (iFLC or sFLC ratio) translated into an improved outcome, whereas UPE or urine IFE status was not prognostic (Figure 24.7). The prognostic value of UPE and sFLCs was further compared when patients who were negative by UPE (after three treatment cycles) were grouped according to their iFLC concentrations or sFLC ratio: those with abnormal FLC parameters had a significantly worse outcome compared with those with normal values (Figure 24.8). By contrast, when patients with elevated iFLC concentrations were separated according to positive/negative UPE results at the same time point, there was no significant difference in PFS between the two groups (Figure 24.8). The authors concluded that the “improved sensitivity and prognostic value of serum over urine measurements provide a strong basis for recommending the former for monitoring LCMM patients”.
Katzmann et al.  assessed the monitoring potential of sFLCs and urinary monoclonal proteins (utilising UPE) in patients with clinically stable monoclonal gammopathy. The authors concluded that sFLCs were measurable in more patients than were urinary monoclonal proteins, and that sFLC measurements exhibited a lower total coefficient of variation (see also Section 7.2.6).
The correlation between serial measurements of sFLCs and urine monoclonal protein (by UPE) in both LCMM or IIMM patients is insufficient to consider the tests interchangeable . Consequently, international guidelines from 2009  recommended monitoring MM patients with sFLCs in the following situations: 1) in all MM patients who do not have sufficient concentrations of measurable serum or urine intact immunoglobulin monoclonal proteins (serum monoclonal protein <10 g/L or a urine monoclonal protein <200 mg/24 hours); and 2) in all MM patients to look for a "stringent complete response" (Chapter 25). However, British guidelines state that there is a “clear rationale” for using sFLC assays “to assess response in light chain only disease, irrespective of the extent of light chain excretion in the urine” (Section 25.6). It seems probable that, as experience and confidence in the sFLC assays grows, they will increasingly replace urine assays for monitoring all patients.