Serum Free Light Chain (SFLC) Elevation Is Associated with High β2-Microglobulin and with a Shorter Time to Treatment in Waldenström Macroglobulinemia (WM).

Abstract

WM is a rare lymphoproliferative disorder caracterised by bone marrow lymphoplasmacytic infiltration with IgM monoclonal gammopathy. Assessing the tumor burden in WM is challenging and is not directly related to IgM level or bone marrow infiltration. Thus treatment criteria are based on clinical symptoms related to IgM or pancytopenia. SFLC quantification is a useful tool for the diagnosis and follow-up of gammopathies such as amyloidosis and light chain myeloma. So far its quantification has never been studied in WM. We investigated whether SFLC quantification was correlated with monoclonal component value and established prognostic factors, or was predictive of a shorter time to treatment. We analyzed 45 untreated WM patients (IgMκ: 37; IgMλ: 8) at the time of diagnosis (n=23) or during the follow-up (n=22). Patients were assessed for physical examination, body CT scan, serum protein electrophoresis with albumin (g/l) and monoclonal component (g/L) measurements, SFLC level (The Binding Site®, cut-off: SFLCκ 19.4 mg/L and SFLCλ 26.3 mg/L), peripheral blood count and β2-microglobulin (β2-m). Cut-off values of prognostic factors were those defined by the International Prognostic Index for WM (Morel ASH 2006) ie. β2-m > 3mg/L, Hb < 115 g/L, platelets < 100 G/L, albumin < 35 g/L. Treatment was initiated at diagnosis in 7 patients or during the follow-up in 23 patients. Median follow-up for the whole population was 15 months (1 – 74). Median SFLCκ value was 39 mg/L (1.73–399), median SFLCλ was 12.6 mg/L (1.93–19400). 75 % of patients had upper to normal SFLC value (34/45). Table 1 summarizes univariate analysis of (1) the relationship between high SFLC value (SFLC > N) and known biological prognostic factors, and (2) the impact of SFLC > N and other biological parameters on time to treatment. Our results showed that high SFLC correlated with β2-m but not with other biological prognostic factors or with monoclonal IgM value. (2) Patients with SFLC > N had a shorter time to treatment than patients with normal SFLC value. Furthermore, taking SFLC as a continuous variable in patients with SFLC > N, treatment time was strongly correlated to the SFLC quantification (κ: p=0.01; λ: p=0.01). SFLC could thus be used as a new marker of tumor burden in WM and its prognostic value must be tested in larger WM series. The correlation between SFLC variation and response to treatment is still under investigation. Table 1 SFLC > N (1) time to treatment (2) SFLC > N NA p=0.03 monoclonal IgM value p=0.08 p=0.001 β2-m > 3 mg/L p=0.03 p=0.44 Hb < 115 g/L p=0.43 p=0.009 Platelets < 100 G/L p=1 p=0.36 Albumin < 35 g/L p=0.3 p=0.011

Abnormal serum free light chain ratios are associated with poor survival and may reflect biological subgroups in patients with chronic lymphocytic leukaemia

“…An abnormal sFLC ratio has been shown to be a risk factor for progression of monoclonal gammopathy of uncertain significance (MGUS) (Rajkumar et al , 2005), solitary plasmacytoma of bone (Dingli et al , 2006) and smouldering multiple myeloma (Dispenzieri et al , 2008). An abnormal sFLC concentration or ratio has also been shown to be prognostic in AL amyloidosis (Dispenzieri et al , 2006), multiple myeloma (Kyrtsonis et al , 2007; van Rhee et al , 2007), and Waldenstrom macroglobulinaemia (Itzykson et al , 2006; Moreau et al , 2006). The production of an M protein in other B‐cell lymphoid malignancies apart from the plasma cell dyscrasias can be detected with varying frequencies (Deegan et al , 1984; Pascali & Pezzoli, 1986; Pascali, 1996).…”