Appraisal of immunoglobulin free light chain as a marker of response

Abstract

The immunoglobulin free light chain (FLC) assay is an invaluable tool for following patients with oligosecretory plasma cell dyscrasia. Baseline values have also been shown to be prognostic in all plasma cell disorders tested. A looming question, however, is the role it should play in following myeloma patients with disease that is measurable using serum and urine electrophoresis. We used the data and stored samples from a mature Eastern Cooperative Oncology Group clinical trial (E9486) to assess serum levels of FLC at baseline and after 2 months of alkylatorbased therapy. For serial determinations, the absolute level of involved serum FLC or the difference of the involved and uninvolved FLC is preferred over the ratio of involved to uninvolved FLC. FLC response after 2 months of therapy was superior to early M-protein measurement to predict overall response. The ideal cut-point for FLC change appears to be between 40% and 50% reduction.

Comparison of serum free light chain and urine electrophoresis for the detection of the light chain component of monoclonal immunoglobulins in light chain and intact immunoglobulin multiple myeloma

“…haematologica | 2016; 101(3) In keeping with previous publications 33 we found poor correlation between sFLC and BJP urine excretion levels in both LCMM (r=0.27) and IIMM (r=0.36) patients. In 4 out of 25 LCMM patients, sFLC reported disproportionately high concentrations of the monoclonal protein relative to UPE; these values may be influenced by the aggregation state of the FLC as previously reported.…”

International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders

“…The authors provide no information about whether very high percentages of reduction were independent of baseline FLC. In contrast, Dispenzieri et al 12 demonstrated that although FLC response at 2 months into alkylator-based therapy predicted for ultimate PEL response, it did not predict for overall or progression-free survival. The major limitation of this study, however, is that the induction chemotherapy employed did not contain novel chemotherapeutic agents.…”

“…36,37 For serial measurements, either the involved FLC or the difference between the involved and uninvolved (dFLC) should be used. 12 Aside from the time of diagnosis and in the context of documenting stringent complete response, the rFLC is not useful because of the not infrequently observed treatment-related immunosuppression of the uninvolved (k for monoclonal l patients and l for monoclonal k patients) FLC during chemotherapy; the ratios generated when one of the FLC numbers is very low will be extreme, reflecting the degree of immunosuppression more than tumor burden.…”

“…Consistently, however, it has been shown that there is not a strong correlation between serum FLC and measurement or urine FLC by 24 h protein electrophoresis. 3,12,15,22,40 When evaluating the performance of changes of serum FLC and of urinary M-spikes over time, there is a relationship to the changes, but to date, no one has shown high correlation coefficients.…”

“…Dispenzieri et al 12 evaluated the relationship between serum FLC and 24-h urine total protein and 24 h urine M protein using 101 patients with baseline iFLC of 5 mg per 100 ml or greater. The correlation coefficients between percentage change of iFLC and urine M protein after 2 months of chemotherapy was poor.…”