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15.3. Prognostic value of the sFLC response in light chain multiple myeloma

Chapter 15

Garcia de Veas Silva et al. [882] studied the prognostic value of sFLCs in 43 patients with LCMM. At diagnosis, patients with an involved sFLC concentration above the median value (κ LCMM: 413mg/L; λ LCMM: 985 mg/L) had a worse prognosis. The median overall survival was 45 months for patients with iFLC concentrations above the median value, and was not reached in those with levels below this value. A highly abnormal sFLC ratio at diagnosis (defined as >43 or <0.01 based on the median values for κ and λ patients, respectively) was also associated with a similar adverse outcome.

Dejoie et al. [914] compared the prognostic value of response assessments based on serum or urine assays, in 111 LCMM patients enrolled onto the IFM-2009 trial [332]. After 3 cycles of treatment, patients whose sFLC results remained abnormal had a significantly worse progression-free survival than those whose results normalised (iFLC: p=0.006; sFLC ratio: p<0.0001). By contrast, a positive UPE or uIFE did not provide prognostic information. These result are discussed further in Sections 20.3.1 and 24.8. The authors also showed that all patients whose sFLC ratio normalised after 3 cycles went on to achieve minimal residual disease (MRD) negativity (measured by flow cytometry) after consolidation treatment, whereas only 78% of uIFE negative patients became MRD negative.

Reid et al. [331][332] determined the prognostic impact of abnormal sFLC ratios in LCMM patients who had become IFE-negative. In a preliminary analysis including 35 LCMM patients, they showed that an abnormal κ/λ sFLC ratio in IFE-negative patients had a negative impact on overall survival. In a separate study, Boyle et al. [336] assessed the prognostic significance of the sFLC response in 122 LCMM patients. Following treatment, patients who achieved both a normal κ/λ sFLC ratio and a normal involved FLC concentration (32/122; 26%) had a significantly longer progression-free survival and overall survival compared to those with a normalisation of their ratio only (50/122; 41%) (p<0.001 and p=0.012, respectively). Both these groups had a better survival than the remaining 40 patients judged to have had a suboptimal response (p=0.012). These studies highlight the prognostic relevance of sFLC measurements in LCMM; sFLC responses are similarly prognostic in patients with intact immunoglobulin MM and this is discussed in more detail in Chapter 20.

Questions

  1. Describe the correlation between serum and urine concentrations of FLCs at diagnosis in patients with LCMM.
  2. Do serum and urine FLC measurements always correlate during monitoring of LCMM?
  3. What may account for the discrepancy between serum and urine FLC results?

Answers

  1. A modest correlation (Section 15.1).
  2. No. Although changes in serum and urine FLC concentrations often correlate when uBJP is present, sFLC measurements can indicate residual disease and/or provide an early indication of relapse in patients with undetectable uBJP (Section 15.2).
  3. Renal metabolism of FLCs, increased sensitivity of sFLC assays and errors in the collection and measurement of urine samples (Section 15.2 and Chapter 24).
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References