High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis

University of Arkansas at Little Rock, Little Rock, Arkansas, United States
Blood (Impact Factor: 10.45). 08/2007; 110(3):827-32. DOI: 10.1182/blood-2007-01-067728
Source: PubMed


Serum-free light chain (SFLC) levels are useful for diagnosing nonsecretory myeloma and monitoring response in light-chain-only disease, especially in the presence of renal failure. As part of a tandem autotransplantation trial for newly diagnosed multiple myeloma, SFLC levels were measured at baseline, within 7 days of starting the first cycle, and before both the second induction cycle and the first transplantation. SFLC baseline levels higher than 75 mg/dL (top tertile) identified 33% of 301 patients with higher near-complete response rate (n-CR) to induction therapy (37% vs 20%, P = .002) yet inferior 24-month overall survival (OS: 76% vs 91%, P < .001) and event-free survival (EFS: 73% vs 90%, P < .001), retaining independent prognostic significance for both EFS (HR = 2.40, P = .008) and OS (HR = 2.43, P = .016). Baseline SFLC higher than 75 mg/dL was associated with light-chain-only secretion (P < .001), creatinine level 176.8 microM (2 mg/dL) or higher (P < .001), beta-2-microglobulin 297.5 nM/L (3.5 mg/L) or higher (P < .001), lactate dehydrogenase 190 U/L or higher (P < .001), and bone marrow plasmacytosis higher than 30% (P = .003). Additional independent adverse implications were conferred by top-tertile SFLC reductions before cycle 2 (OS: HR = 2.97, P = .003; EFS: HR = 2.56, P = .003) and before transplantation (OS: HR = 3.31, P = .001; EFS: HR = 2.65, P = .003). Unlike baseline and follow-up analyses of serum and urine M-proteins, high SFLC levels at baseline-reflecting more aggressive disease-and steeper reductions after therapy identified patients with inferior survival.

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    • "Recent data have shown that serum free light chains and their ratio may constitute prognostic factors in CLL [9] [10] [11] [12] [13] [14] [15]. Serum free light assays have already been shown to improve detection, management, and prognostication in plasma cell dyscrasias [16] [17] [18]. In diffuse large B-cell lymphomas, increased levels of sFLC were shown to be an independent, adverse prognostic factor for overall survival (OS). "
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    ABSTRACT: Background. Serum free light chains (sFLC), the most commonly detected paraprotein in CLL, were recently proposed as useful tools for the prognostication of CLL patients. Objective. To investigate the prognostic implication of sFLC and the summated FLC-kappa plus FLC-lambda in a CLL patients' series. Patients and Methods. We studied 143 CLL patients of which 18 were symptomatic and needed treatment, while 37 became symptomatic during follow-up. Seventy-two percent, 18%, and 10% were in Binet stage A, B and C, respectively. Median patients' followup was 32 months (range 4-228). Results. Increased involved (restricted) sFLC (iFLC) was found in 42% of patients, while the summated FLC-kappa plus FLC-lambda was above 60 mg/dL in 14%. Increased sFLC values as well as those of summated FLC above 60 were related to shorter time to treatment (P = 0.0005 and P = 0.000003, resp.) and overall survival (P = 0.05 and P = 0.003, resp.). They also correlated with β 2-microglobulin (P = 0.009 and P = 0.03, resp.), serum albumin (P = 0.009 for summated sFLC), hemoglobin (P < 0.001), abnormal LDH (P = 0.037 and P = 0.001, resp.), Binet stage (P < 0.05) and with the presence of beta symptoms (P = 0.004 for summated sFLC). Conclusion. We confirmed the prognostic significance of sFLC in CLL regarding both time to treatment and survival and showed their relationship with other parameters.
    Full-text · Article · Oct 2013 · Advances in Hematology
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    • "In over 80% of plasma cell disorders the neoplastic clone secretes a measurable amount of an intact monoclonal immunoglobulin, and although sFLC concentration is abnormal in most patients [Mead et al. 2004], the assay does not add any practical information to the whole diagnostic procedure , so that the gold standard for diagnosis is still represented by serum protein electrophoresis and immunofixation. Due to the short half-life of FLCs (2–6 h, compared with 21 days for intact immunoglobulin G), the assay can be useful potentially for earlier monitoring of the efficacy of a given therapeutic program [Pratt et al. 2006; Hajek et al. 2007], although the impact of these data on patients' outcome is still a matter of debate [van Rhee et al. 2007]. Oligosecretory MM are conditions in which the amount of monoclonal protein secreted by the neoplastic clone is much smaller than that expected by the evaluation of the tumor load; disease monitoring usually includes repeated testing of the bone marrow plasma cell infiltration and/or bone imaging [Durie et al. 2006]. "
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    ABSTRACT: Diagnosis and monitoring of multiple myeloma (MM) and related conditions are usually carried out by means of serum and urine protein electrophoresis and immunofixation. In the early 2000s, an assay aimed at evaluating serum free light chains (sFLCs) was made available and subsequently tested in different plasma cell disorders. Several reports have demonstrated the usefulness of the assay for the diagnosis and monitoring of oligosecretory MM, nonsecretory MM, Bence Jones MM, and amyloid light-chain amyloidosis. Furthermore, a prognostic role for an abnormal sFLC κ/λ ratio has been observed in the case of monoclonal gammopathy of unknown significance, smoldering MM, solitary plasmacytomas, and in newly diagnosed symptomatic MM secreting intact monoclonal immunoglobulins. In conclusion, according to present data, the sFLC assay can be considered reliable for the diagnosis, monitoring, and prognosis of different plasma cell disorders, and recently studies have been carried out to test a possible role of an sFLC evaluation in other B-cell lymphoproliferative malignancies.
    Preview · Article · Feb 2013
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    • "After stem cell transplantation, there are often minor fluctuations in free light chain levels in completely responding patients and some caution is required in interpreting results that are borderline. Prospective trials are required to assess whether the presence of an abnormal FLC ratio in patients otherwise in CR is indicative of outcome, as suggested by small studies post-transplant (Sirohi et al, 2003; Reid et al, 2004), and if it has any value in determining further treatment strategies. "
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    ABSTRACT: Over the last few years new immunoassays have emerged that allow the measurement of free immunoglobulin light chains (FLCs) in serum to a level of 2-4 mg/l and provide a much greater sensitivity than older methods, such as immunofixation, which is able to detect FLCs at a minimum concentration of 100-150 mg/l. The new FLC assay has enabled the detection of monoclonal protein in some patients with non-secretory myeloma and amyloidosis that were previously undetectable. FLC measurements are quantitative, correlating with disease activity, and are an advance in monitoring light chain only multiple myeloma, AL amyloidosis, non-secretory and oligo-secretory multiple myeloma. Serum FLC concentrations also reflect the disease course in the majority of myeloma patients producing intact monoclonal immunoglobulin proteins and have been incorporated into the new response criteria. The rapid half life of lambda and kappa free light chains means that FLC assays may provide a more rapid indication of the response to treatment but their clinical utility in this setting needs further study. An abnormal FLC ratio has been shown to be a risk factor for progression of monoclonal gammopathy of undetermined significance, smouldering myeloma and solitary plasmacytoma of bone and is prognostic in multiple myeloma.
    Full-text · Article · Jun 2008 · British Journal of Haematology
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