SECTION 2 - Free light chains and monoclonal gammopathies

Fig 7.0 Monoclonal gammopathies diagnosed at the Mayo Clinic during 2005.

The main clinical applications of serum free light chain (sFLC) measurements are for patients with monoclonal gammopathies (Chapter 29). Figure 7.0 shows the associated diseases seen at the Mayo Clinic in 2005 ^[1]. These data are from a specialist referral centre; general hospitals see different patterns of disease referral with a higher percentage of MM and MGUS and fewer AL amyloidosis patients.

Table 7.0 shows the approximate annual incidence of the more common monoclonal gammopathies reported in the USA. Over the past 10 years, there have been publications covering many aspects of FLC usage in light chain multiple myeloma (LCMM), nonsecretory multiple myeloma (NSMM) and AL amyloidosis while its benefits in MGUS are now well established. Other clinical applications have recently been described including in solitary plasmacytomas, smouldering (asymptomatic) multiple myeloma (SMM), Waldenström’s macroglobulinaemia (WM) and B-CLL all of which are described in their respective chapters.

Dispenzieri et al. ^[2] recently suggested that these observations on sFLCs represent an important step in understanding monoclonal gammopathies and add to previous definitions. 1^st, there was the separation of polyclonal and monoclonal hypergammaglobulinemia. 2^nd, there was the realization that premalignant MGUS existed. 3^rd, the concept of SMM became an accepted principle. 4^th, there was an international consensus on the definitions for the spectrum of MGUS to SMM to active MM. Each of these benchmark decisions were based upon observational studies that incorporated the following four variables to reach conclusions and recommendations:

1. Monoclonal protein; 2. Bone marrow plasmacytosis; 3. Symptom status; 4. Time.

They proposed that sFLC κ/λ ratios should be introduced as another variable that may better define these clinical entities. It is a simple test that provides information about underlying plasma cell biology and baseline sFLC κ/λ ratios provide valuable prognostic information. Furthermore, all recent studies indicate that in the spectrum of disease development from MGUS, through ASMM to symptomatic MM, increasing monoclonal FLC production becomes progressively more probable. This accumulating evidence has led to new international guidelines (Chapter 25) where sFLC analysis is recommended in patient diagnosis and prognosis, as well as the management of a number of the individual conditions ^[3].

The following chapters review these studies and suggest investigations that may be of clinical value in the future. In addition, there are many other studies showing the importance of sFLCs when screening for monoclonal diseases, replacement of urine testing, their role in patient monitoring, etc. (Section 4). There is even the probability of reversing myeloma kidney damage with the combination of novel “high cut-off” haemodialysis and chemotherapy (Chapter 13).

Table 7.0. Incidence of diseases producing monoclonal proteins in the USA ^[4]. *% showing monoclonal proteins by traditional electrophoretic methods. ** Based on current publications. ^#Other B-cell lymphoid malignancies also produce monoclonal immunoglobulins. IIMM: intact immunoglobulin multiple myeloma, LCDD: light chain deposition disease, B-CLL: B-cell chronic lymphocytic leukaemia.

References