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8.6.2. Diagnostic performance in MM

Chapter 8

One major drawback of using monoclonal antibody-based FLC assays is that these assays have the potential to miss a particular monoclonal FLC clone. This is most serious when there is the greatest reliance on sFLC assays to identify a monoclonal protein that would otherwise be hidden or absent by standard electrophoretic techniques. This is often the case in LCMM and NSMM. An increasing number of publications suggest that both N Latex FLC and Seralite-FLC assays can fail to detect certain FLC tumour clones.

In a total of six studies published to date, which incorporated approximately 80 LCMM patients, the Siemens N Latex FLC assays failed to detect abnormalities in six λ LCMM and one κ LCMM patients (Table 8.7) [201][175][209][923][952][219]. By comparison, the same six studies reported that all of these LCMM patients were correctly identified by the Freelite assays. The best described cohorts of confirmed cases of LCMM were included in the studies by Schneider and Hoedemakers [209][219] in which 3/26 of confirmed LCMM cases were not detected by the N Latex FLC assays. In contrast, an abnormal Freelite κ/λ sFLC ratio has been detected in all of 692 LCMM patients at diagnosis (Chapter 15).


Study Total no. of
LCMM patients
Missed LCMM N Latex FLC Freelite
κ FLC
mg/L
λ FLC
mg/L
κ/λ ratio κ FLC
mg/L
λ FLC
mg/L
κ/λ ratio
Lock 2013 [201]n.s
(189 MM)
λ LCMM 19.5 59.7 0.33
Normal
4.66 6070 <0.01
Abnormal
λ LCMM 12.8 40.2 0.32
Normal
7.9 422 0.02
Abnormal
Hoedemakers 2011 [209]3 κ LCMM
6 λ LCMM
λ LCMM n.s n.s n.s
Normal
n.s n.s n.s
Abnormal
Schneider 2013 [219]17 LCMM λ LCMM n.s n.s 0.8
Normal
n.s n.s 0.02
Abnormal
κ LCMM n.s n.s 0.8
Normal
n.s n.s 1.89
Abnormal
Sabatino 2017 [952]

1 λ LCMM λ LCMM 16.5 23.0 0.71
Normal
9.14 818.8 0.01
Abnormal
Pretorius 2012 [175]n.s λ LCMM 29 84 0.35
Normal
18 464 0.04
Abnormal

Table 8.7. Summary of missed cases of LCMM by N Latex FLC assays. Patients were categorised as misclassified if the N Latex FLC assays reported a normal κ/λ ratio (n.s. = not stated).

Heaney et al. [980] compared Freelite and Seralite-FLC results in 325 light chain MM (LCMM) and 37 nonsecretory MM (NSMM) patients. All 325 LCMM patients had abnormal Freelite κ/λ ratio at diagnosis, but 3/325 patients had a normal Seralite-FLC ratio. In all three cases, the iFLC Freelite concentration was >100 mg/L, suggesting that the Seralite-FLC assay either missed epitopes or had insufficient analytical sensitivity. Similar results were found in NSMM at diagnosis: 49% (18/37) patients had an abnormal Freelite sFLC ratio but only 32% had an abnormal Seralite-FLC sFLC ratio.

The recommendation that sFLC analysis plus serum electrophoresis constitutes a suitable primary screening protocol for monoclonal gammopathies [136][167] should, arguably, only be applied to FLC analysis with Freelite assays and not N Latex FLC or Seralite-FLC assays, which have the potential to miss patients and are not validated in this context.

References