Abstract
The serum free light chain (SFLC) assay is useful in detecting monoclonal protein when there no detectable M protein on immunofixation electrophoresis (IFE). There are limited data on its value when IFE is positive. In a small series of 5 patients achieving CR, normalization of SFKLR was found to precede IFE negativity by a few weeks (Moesbauer et al. ASH 2005). Results on 231 serum samples from myeloma patients (most on therapy) where serum IFE showed IgA κ (n=33), IgA λ (n=13), IgG κ (n=153), or IgG λ (n=32), and where simultaneous SFLC and immunoglobulin (Ig) estimation had been performed were analyzed. Samples with >1 monoclonal band or multiple oligoclonal bands were excluded. The serum free κ:λ ratio (SFKLR; normal 0.26–1.65) was abnormal in 113 (49%) and normal in 118 (51%). IgG and IgA levels were compared in the context of normal versus abnormal SFKLR within each of the 4 isotypes (IgA κ, IgAλ, IgG κ, IgG λ). The table below shows that involved Ig levels were higher with abnormal than with normal SFKLR. However, uninvolved Ig levels were higher with normal than with abnormal SFKLR suggesting that normalization of SFKLR may mark a response to therapy - improved uninvolved Ig levels being evidence of response.
| Monoclonal protein | Immunoglobulin | Abnormal SFKLR | Normal SFKLR | P |
|---|---|---|---|---|
| IgA kappa | IgA | 1640 (190–4000) | 515 (102–2230) | 0.048 |
| IgA kappa | IgG | 419 (118–1120) | 404 (197–1740) | 0.39 |
| IgA lambda | IgA | 408 (159–696) | 704 (180–779) | 0.17 |
| IgA lambda | IgG | 619 (495–1510) | 1530 (533–1700) | 0.025 |
| IgG kappa | IgA | 42 (7–225) | 94 (7–642) | 0.0009 |
| IgG kappa | IgG | 1490 (585–5560) | 1260 (327–2690) | 0.004 |
| IgG lambda | IgA | 32 (7–121) | 96 (19–562) | 0.047 |
| IgG lambda | IgG | 2060 (555–12300) | 1050 (432–2830) | 0.018 |
| Monoclonal protein | Immunoglobulin | Abnormal SFKLR | Normal SFKLR | P |
|---|---|---|---|---|
| IgA kappa | IgA | 1640 (190–4000) | 515 (102–2230) | 0.048 |
| IgA kappa | IgG | 419 (118–1120) | 404 (197–1740) | 0.39 |
| IgA lambda | IgA | 408 (159–696) | 704 (180–779) | 0.17 |
| IgA lambda | IgG | 619 (495–1510) | 1530 (533–1700) | 0.025 |
| IgG kappa | IgA | 42 (7–225) | 94 (7–642) | 0.0009 |
| IgG kappa | IgG | 1490 (585–5560) | 1260 (327–2690) | 0.004 |
| IgG lambda | IgA | 32 (7–121) | 96 (19–562) | 0.047 |
| IgG lambda | IgG | 2060 (555–12300) | 1050 (432–2830) | 0.018 |
However, does normalization of SFKLR universally herald IFE negativity? This is an important unanswered question because SFKLR is normal in a high proportion of samples which still show monoclonal protein on IFE. The figures below show scatter plots of IgG and IgA for each of the 4 isotypes for normal vs abnormal SFKLR. Within each plot, there is no obvious pattern distinguishing normal (x) from abnormal (o) SFKLR. However, there are a number of normal SFKLR points with high involved and low uninvolved Ig levels where a normal SFKLR is difficult to explain.
We conclude that the SFLC assay often reveals normal SFKLR even when there is a detectable monoclonal protein in the serum. Whether this always predicts eventual paraprotein clearance and achievement of IFE negativity in patients on therapy is unknown, and needs to be studied prospectively.
Disclosure: No relevant conflicts of interest to declare.
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