Seralite© Rapid Point-Of-Care Detection Of Free Light Chain Escape, Non-Secretory Relapse and Light Chain Only Relapse In Multiple Myeloma

Free light chain (FLC) testing in serum is a more sensitive method of monitoring FLC secretion from myeloma cells than FLC testing in urine because FLC do not appear in urine until their secretion exceeds the renal tubule threshold for FLC reabsorption. Serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE) are insensitive methods of detecting FLC in serum. In 2002 quantitative detection of serum FLC by turbidimetric and nephelometric assays using polyclonal sheep anti-sera specific for FLC (Freelite®) became available; this has become the internationally recommended method of measuring FLC levels in serum. Two thirds of non-secretory (NS) patients who are IFE negative in serum and urine have abnormal FLC levels in serum and might be better classified as oligosecretory light chain only (LCO) patients. Serum FLC testing is particularly useful in diagnosis and monitoring of these and conventional LCO patients in whom FLC are detectable in urine when their disease is very active. In 5% IgG and 10% IgA M-protein myeloma patients, relapse is characterised by an increase in abnormal serum FLC without a corresponding increase in whole M-protein, termed ‘free light chain escape’ and their relapse is detected earliest by serum FLC testing.

Despite the clinical advantages of serum FLC testing, existing quantitative serum FLC assays are restricted to centralised laboratories. The time between venesection and availability of FLC results, for most clinicians, varies from days to weeks. This delays diagnosis and delays changes in clinical management when assessing response or monitoring for relapse. We have developed a second generation of serum FLC tests that utilise monoclonal rather than polyclonal anti-FLC antibodies. One result of this new generation of assays has been the development of a new rapid serum FLC test (Seralite®, Serascience Ltd, Oxford UK) that provides point of care measurement of serum FLC levels in just ten minutes.

We assessed FLC levels at diagnosis, remission and relapse in 31 patients diagnosed with intact immunoglobulin myeloma who relapsed with abnormal serum FLC but without an increase in M-protein level (termed ‘light chain escape’). In all evaluable samples, Seralite® detected an abnormal serum FLC level at diagnosis, followed by a normalisation of the serum FLC ratio during remission, and a subsequent abnormal FLC level at relapse. Seralite® FLC results correlated diagnostically with the existing laboratory serum FLC assay for all samples.

Additionally, we analysed FLC levels at diagnosis, remission and relapse in 166 myeloma patients characterised as having no intact immunoglobulin M-protein by serum IFE at diagnosis. 16% had a negative urine IFE and were identified only by the presence of an abnormal FLC ratio in their serum (NS or oligosecretory LCO). The remaining 84% had FLC detected in urine by IFE at diagnosis (conventional LCO). All diagnosis samples had an imbalanced FLC ratio detected by Seralite®. With a median follow-up of over 5 years, 83% of these patients relapsed with abnormal serum FLC levels. Half of the conventional LCO patients were IFE negative in the urine at relapse. Seralite® FLC results correlated diagnostically with the existing laboratory FLC assay for all samples.

In summary, Seralite® detected abnormal serum FLC levels in all myeloma patients relapsing with light chain escape, and patients relapsing with non-secretory (oligosecretory LCO) and conventional LCO myeloma. There were no false negatives and no false positives supporting the use of Seralite® for the monitoring of these distinct myeloma patient groups.