Abstract
We investigated the prognostic impact and clinical utility of serum free light chains (sFLC) and serum heavy-light chains (sHLC) in patients with multiple myeloma treated according to the GEM2005MENOS65, GEM2005MAS65, and GEM2010MAS65 PETHEMA/GEM phase III clinical trials. Serum samples collected at diagnosis were retrospectively analyzed for sFLC (n = 623) and sHLC (n = 183). After induction or autologous transplantation, 309 and 89 samples respectively were available for sFLC and sHLC assays. At diagnosis, a highly abnormal (HA) sFLC ratio (sFLCr) (<0.03 or >32) was not associated with higher risk of progression. After therapy, persistence of involved-sFLC levels >100 mg/L implied worse survival (overall survival [OS], P = 0.03; progression-free survival [PFS], P = 0.007). Among patients that achieved a complete response, sFLCr normalization did not necessarily indicate a higher quality response. We conducted sHLC investigations for IgG and IgA MM. Absolute sHLC values were correlated with monoclonal protein levels measured with serum protein electrophoresis. At diagnosis, HA-sHLCrs (<0.29 or >73) showed a higher risk of progression (P = 0.006). Additionally, involved-sHLC levels >5 g/L after treatment were associated with shorter survival (OS, P = 0.001; PFS, P = 0.018). The HA-sHLCr could have prognostic value at diagnosis; absolute values of involved-sFLC >100 mg/L and involved-sHLC >5 g/L could have prognostic value after treatment.
Highlights
The immunoassay for quantifying free immunoglobin light chains in serum has been a valuable tool for diagnosing and monitoring light-chain multiple myeloma (MM) [1], amyloid light-chain amyloidosis, [2], and monoclonal gammopathies of undetermined significance (MGUS) [3,4]
Of 819 included patients, serum samples for serum free light chains (sFLC) and serum heavy-light chains (sHLC) analyses were available at the time of diagnosis in 623 and 183 cases, respectively
When we analyzed only patients with a partial response, we found that an absolute value of involved-sFLC !100 mg/L after treatment was associated with a higher risk of progression
Summary
The immunoassay for quantifying free immunoglobin light chains in serum (sFLC) has been a valuable tool for diagnosing and monitoring light-chain multiple myeloma (MM) [1], amyloid light-chain amyloidosis, [2], and monoclonal gammopathies of undetermined significance (MGUS) [3,4]. The recently developed assays for quantifying specific immunoglobin heavy-light chain complexes in serum (sHLC) have enabled accurate measurements of the different types of light chains (termed κ and λ) coupled with a specific heavy chain (i.e., IgA, IgG, or IgM) in intact immunoglobulins. The ratios of heavy-light chain-κ to heavy-light chain-λ can be determined (e.g., the IgG-κ:IgG-λ ratio) The latter assay has made it possible to measure isotype-specific suppression of the sHLC pair that is not involved with the disease, such as the suppression of IgA-λ in a patient with IgA-κ type MM [5,6]. In addition to its diagnostic utility [3], an abnormal sFLC ratio (sFLCr) is a risk factor for progression from MGUS, smoldering myeloma, or solitary plasmacytoma to symptomatic MM. Some studies have reported a relationship between baseline levels of the involved-sFLC level or the sFLCr and the disease burden; other studies have not found any relationship [1,4,7,9,10,11]
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