The Value Of Serum Free Light Chain Monitoring Compared To Urinary Bence-Jones Measurement In Light Chain Only Myeloma

The significant subset of myeloma patients (MM) who only secrete light chains are referred to as light chain only myelomas (LCO). These patients represent 16% of all cases. Although, Bence-Jones proteinuria (BJ) is classically used to monitor these patients, cases with negative Bence-Jones proteinuria (BJ) but positive serum free light chains (sFLC) have been reported.

The aim of this study was to quantify these patients and determine whether sFLC could be used instead of BJ to monitor disease response in LCO patients.

1960 newly diagnosed myeloma patients were enrolled in the myeloma IX trial (ISRCTN68454111) to receive depending on their age and performance status either an intensive or non-intensive treatment. Response was assessed depending on the trial arm at 3 months post end of induction or 6 weeks and 100 days post transplant. Response was assessed based on the IMWG criteria. Data was analysed using the SPSS version 19.0 (SPSS Inc., Chicago, USA) software and survival estimated using the Kaplan-Meier method.

259 patients were identified as being LCO among which 86% (n=223) were BJ positive. 166 were evaluated for sFLC (68%) among which 16% had a negative BJ (n=26). As expected, median values of sFLC were higher in the presence of a BJ proteinuria [median kappa: 3313 (1151-8381), median lambda: 2687 (1274-6099)] than in the negative group [median kappa: 438 (51-791), median lambda: 313 (69-609)] (p<0.05). Data on best response achieved were available for 122/166 of these patients (73.5%). 26% patients (n=32) had both a normal ratio and a normal value of their involved sFLC and 41% of patients (n=50) had a normal ratio but still had an abnormal involved sFLC. The remaining 40 patients were considered to have a sub-optimal response. Patients who normalized both the ratio and sFLC values had a significantly longer Progression Free Survival (PFS) and Overall survival (OS) compared to patients that normalized their ratio only. Both these groups had a better survival than those who failed to achieve an optimal response [median PFS were respectively 43.3, 33.0 and 18.8 months (p<0.001) and median OS were respectively 85.3, 69.9 and 45.5 months, (p=0.012)]. Furthermore, this survival benefit was seen in patients with an involved sFLC within the normal range irrespective of their sFLC ratio. With a median follow up of 5.9 years 138 patients (83%) have relapsed. Complete data at relapse are available in 46% of them. sFLC at relapse were abnormal in 100% of patients. In 23/55 (42%) of the BJ positive patients at diagnosis, relapse was identified only by an increase in the sFLC, whilst 4/8 BJ negative patients relapsed with a measurable paraprotein.

BJ proteinuria cannot be detected until the production of sFLC is greatly raised, leading to a misclassification of 16% of LCO MM patients as being non-secretory. This could be of clinical relevance as it may help prevent end organ damage to the kidney. We were able to show, in a large cohort of newly diagnosed MM patients, that sFLC are imbalanced in virtually all evaluated LCO MM patients. This data also suggests that both the ratio and the absolute value of sFLC are important in predicting outcome after treatment. Furthermore, the sFLC ratio, although essential for the diagnosis, may be less reliable to assess response due to a low non-involved chain and delayed immune reconstitution.

The correct identification of a myeloma clone secreting only light chains has important clinical relevance. The sFLC assay enables us to efficiently diagnose and monitor patients and should therefore be standard practice when there is not a measurable paraprotein on serum protein electrophoresis.

Leleu:CELGENE: Honoraria; JANSSEN: Honoraria. Morgan:Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Millenium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Johnson and Johnson: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees.