Chapter 20


  • sFLC and Hevylite® ratios plus sFLC and Hevylite absolute values can provide prognostic information for multiple myeloma patients, independently of other prognostic markers.
  • Prognostic value has been reported at all stages of the disease process and in association with various treatment regimens.
  • sFLC and Hevylite analysis can improve prognostic power when used alongside other markers, e.g. in association with the International Staging System.

The outcome for patients with multiple myeloma (MM) is highly variable, and understanding the prognosis for a particular patient can help when selecting the intensity of treatment to be used and the frequency of review, as well as being necessary for stratifying patients before entry into trials. This is true during and after treatment as well as at the initial diagnosis. The International Myeloma Working Group (IMWG) guidelines for risk stratification published in 2011 [428] state that the International Staging System (ISS) [429] is applicable as a prognostic system in the majority of settings (Table 20.1 and Section 25.3.4).

Stage Criteria Median Survival
ISerum β2M <3.5 mg/L and serum albumin ≥35 g/L 62 months
IISerum β2M <3.5 mg/L but serum albumin <35 g/L; or serum β2M between 3.5 and <5.5 mg/L, irrespective of the serum albumin level 44 months
IIISerum β2M ≥5.5 mg/L 29 months

Table 20.1. International Staging System [429]. β2M: β2-microglobulin.

The authors of the ISS [429], published in 2005, proposed the use of just serum albumin and β2-microglobulin (β2M) measurements, with the intention of making the system inexpensive and available to the maximum number of institutes. The authors’ analysis did show, however, that many other serum markers (e.g. creatinine, calcium, platelet count, lactate dehydrogenase, type and size of monoclonal protein) and physical factors (age, extent of lytic lesions, bone marrow plasma cell [BMPC] infiltration) were also prognostic to varying degrees. However, serum free light chain (sFLC; Chapter 5) and immunoglobulin heavy/light chain (Hevylite, HLC; Chapter 9) assays were not available when the study was initiated and cytogenetic data was only available for a small subset of the study population. The prognostic value of genetic abnormalities has now been studied widely, and their assessment by techniques such as fluorescence in situ hybridization (FISH) has shown that they can have greater prognostic power than more traditional markers [430][431][432]. IMWG guidelines recognise that cytogenetics and FISH analysis play an important and independent role in risk stratification [428]. Nevertheless, such analyses are still relatively expensive and available only at specialist centres.

The monoclonal protein size and type has frequently been investigated as a potential predictor of patient outcome in MM. Before the development of the ISS, the most widely used staging system was that devised by Durie and Salmon [433] and this incorporated the size of the monoclonal protein as one of the prognostic variables. In an analysis of data from 2592 patients who had participated in UK myeloma trials. Drayson and colleagues [247] corroborated results from earlier studies [429][435][436][437] by demonstrating that patients with light chain MM (LCMM) had shorter survival than those with intact immunoglobulin MM (IIMM). The authors’ concluded that this was a result of the increased incidence of renal failure in LCMM patients, which could be attributed to the higher levels of urinary FLC excretion in this group. Increased renal failure and shortened survival times were also seen in IIMM patients who had elevated urine FLC concentrations similar to those in LCMM. Similar findings were reported by Yadav et al. [953], who confirmed that high levels of sFLCs (>700 mg/L) was one of the strongest predictors of renal function in newly diagnosed MM patients.

Therefore, since previous studies have found that levels of both serum monoclonal immunoglobulin and urine FLCs are related to MM patient survival, serum HLC and sFLC analysis may provide better predictions. The purpose of this chapter is to present the studies that have investigated sFLC and HLC analysis as prognostic markers at each stage of MM development.