The Utility of Serum Free Light Chain Measurement in Myeloma Patients with Oligoclonal Bands on Serum or Urine Immunofixation

Abstract

During treatment, patients with myeloma can develop restricted bands in the serum or urine that are different from the original M protein on serum (SIFE) and urine (UIFE) immunofixation electrophoresis. These so-called oligoclonal bands represent transient aberrant recovery of the immune system, and are not associated with any adverse implications. Unless SIFE/UIFE are checked and the bands identified as oligoclonal, a mistaken diagnosis of persistent or recurrent disease may be made. It is not known if the pattern of serum free light chain (SFLC) levels helps differentiate between oligoclonal bands and persistent/recurrent M protein.Data on 219 myeloma patients with serial follow-up were evaluated to identify 3537 encounters which fulfilled the following criteria: available SFLC levels, and 1 or more restricted bands identified on SIFE or UIFE. Patients with non-secretory and biclonal disease were excluded. If a heavy or light chain not part of the original M protein was seen, the presence of an oligoclonal band was diagnosed. If the original M protein was identified intact (e.g. the detection of IgG kappa in a patient with IgG kappa myeloma) or its constituent heavy or light chain were identified in an unbound fashion (e.g. the detection of free IgG or free kappa in a patient with IgG kappa myeloma), the original M protein was felt to be present. Results with oligoclonal bands were further characterized by the additional presence or absence of the original M protein.Only the original M protein was seen in 2661 (75%), 352 (10%) had oligoclonal bands without the original M protein, and an oligoclonal band was seen with the original M protein in 524 (15%). The SFLC ratio was normal (0.26–1.65) in 1306 (37%) and abnormal in 2231 (63%).The relationship of the nature of the restricted bands seen with the SFLC ratio was assessed in two ways in preliminary analysis. In the first, the SFLC ratio was classified as normal or abnormal. In the second, abnormal ratios were classified further as concordant (<0.26 for lambda disease and >1.65 for kappa disease) or discordant (<0.26 for kappa disease and >1.65 for lambda disease). Discordant ratios were grouped with normal because they did not reflect an excess of the abnormal light chain associated with the original M protein. The following table shows the relationship between the nature of the restricted bands and the SFLC ratio:SFLC ratioSFLC ratioRestricted band categoryNormalAbnormalNormal or discordant abnormalConcordant abnormalOriginal M protein only843 (32%)1818(68%)919 (35%)1742 (65%)Oligoclonal band(s) only185 (53%)167(47%)215 (61%)137 (39%)Oligoclonal band(s) with original M protein278 (53%)246 (47%)302 (58%)222 (42%)P<0.0001<0.0001As the table shows, the SFLC ratio was normal significantly more frequently when oligoclonal bands were present. This appeared to be unaffected by the presence of bands resembling the original M protein.As the SFLC ratio can be affected by treatment-induced suppression of the uninvolved free light chain, the data were also analyzed as follows: concordant abnormal SFLC ratio with elevated involved free light chain (1890; 53%) versus the rest (1647; 47%). Finally, based on the hypothesis that elevated uninvolved free light chain levels are less likely to be seen with active disease, readings with elevated uninvolved free light chains were transferred from the former category into the latter. The following table shows the relationship between the nature of the restricted bands and the above categories:SFLC ratioSFLC ratioRestricted band categoryNormal (All others)Abnormal (Concordant abnormal with elevated involved free light chain)Normal (All others)Abnormal (Concordant abnormal with elevated involved free light chain; excluding elevated uninvolved free light chain)Original M protein only1246 (47%)1415 (53%)1299 (49%)1362 (51%)Oligoclonal band(s) only247 (70%)105 (30%)257 (73%)95 (27%)Oligoclonal band(s) with original M protein343 (65%)181 (35%)361 (69%)163 (31%)P<0.0001<0.0001Once again, as the table shows, the SFLC ratio was normal (or equivalent of normal) significantly more often when oligoclonal bands were present.We conclude that the SFLC ratio is significantly more likely to be normal when oligoclonal bands are present in patients with myeloma. However, the differences between patients with and without oligoclonal bands are not definitive enough to predict the nature of the bands seen. SIFE and UIFE remain the only definitive means of identifying the nature of the restricted bands seen in patients with myeloma on therapy.