Normalization of free light chain kappa/lambda ratio is a robust prognostic indicator of favorable outcome in patients with multiple myeloma

2013 ◽  
Vol 90 (2) ◽  
pp. 134-141 ◽  
Author(s):  
Kan-ichi Iwama ◽  
Dai Chihara ◽  
Kenji Tsuda ◽  
Tomotaka Ugai ◽  
Hiroyuki Sugihara ◽  
...  
Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4880-4880
Author(s):  
Efstathios Koulieris ◽  
Stephen Harding ◽  
Marie-Christine Kyrtsonis ◽  
Caroline Bradley ◽  
Mark T Drayson ◽  
...  

Abstract Abstract 4880 Serum free light chain ratios (FLCr) are important prognostic markers in B cell malignancies and their measurement has recently been included in multiple myeloma (MM) international guidelines. In contrast, serum IgG and IgA concentrations are not prognostic in MM. Novel immunoassays have been developed which target the specific conformational, junctional epitopes between the heavy and light chains of the immunoglobulin making it possible to measure Ig'kappa and Ig'lambda and produce an Ig'kappa /Ig'lambda ratio. Here we describe the use of FLCr and heavy/light chain ratios (HLCr) to predict survival in MM patients. Archived sera from a historic MRC and a more recent Velcade, Adriamycin, dexamethazone (PAD) MM trail were utilised and the data combined using each study as a categorical variable. 85 MRC and 73 PAD samples were analysed retrospectively using serum free light chain and serum heavy / light chain nephelometric assays (The Binding Site Group). Kaplan Meier curves and Cox regression analysis were constructed comparing the upper quartile to the lower three quartiles for involved intact immunoglobulin, FLC, HLC and FLC + HLC. All analysis was completed using SPSS v14.0. FLCr and HLCr values were not correlated (Pearson's = -0.037 p=0.66). There was no significant difference in survival when comparing the lower three quartiles and upper quartile of the involved intact immunoglobulin (Hazard Ratio [HR]=1.16: p=0.585). However, comparison of the upper quartile to the lower three quartiles did reveal significant differences in survival times for FLCr (HR=2.16: p=0.003), HLCr (HR=1.94: p=0.01) and FLCr+HLCr (HR=3.34: p=0.001). Intact immunoglobulin concentration was not prognostic in this study in keeping with current international prognostic guidelines. As with previously published data, FLCr was a prognostic indicator in MM (van Rhee 2007, Kyrtsonis 2007). It is likely FLCr is more predictive of outcome than the concentration of tumour FLC production (data not shown) because it includes a measure of immunoparesis. HLCr was an independent prognostic indicator of survival in this study. HLCr measurement may be superior to intact immunoglobulin in predicting outcomes because: 1) Changes in haematocrit and plasma volume in MM can cause Ig to change by more than 50% regardless of tumour production. 2) Serum IgG is susceptible to variable clearance rates (related to saturation of the FcRn receptor for IgG). 3) Ig measurements using serum protein electrophoresis or nephelometry include all or some of the non-tumour Immunoglobulins and may be non-linear. The summated FLCr and HLCr is a stronger prognostic marker than either measurement independently. This maybe because, as shown by Ayliffe (2007) myeloma cells can produce intact immunoglobulin, FLC or both. Therefore, in patients with very low intact immunoglobulin production and high FLC production, FLCr is likely to be the most prognostic marker and visa versa for patients with low FLC production. Conclusion In this combined study FLCr, HLCr and FLCr + HLCr were found to be predictive of overall survival in MM patients. Larger studies comparing HLCr and FLCr with B2M and Albumin as used in the international staging system are needed. Disclosures Harding: The Binding Site Group Ltd: Employment. Bradley:The Binding Site Group Ltd: Employment. Bradwell:The Binding Site Group Ltd: Shareholder.


2021 ◽  
pp. 1-8
Author(s):  
Charlotte Gran ◽  
Gabriel Afram ◽  
Johan Liwing ◽  
Andre Verhoek ◽  
Hareth Nahi

2018 ◽  
Vol 93 (10) ◽  
pp. 1207-1210 ◽  
Author(s):  
Marcella Tschautscher ◽  
Vincent Rajkumar ◽  
Angela Dispenzieri ◽  
Martha Lacy ◽  
Morie Gertz ◽  
...  

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Jennifer L. J. Heaney ◽  
John P. Campbell ◽  
Punit Yadav ◽  
Ann E. Griffin ◽  
Meena Shemar ◽  
...  

Blood ◽  
2007 ◽  
Vol 110 (3) ◽  
pp. 827-832 ◽  
Author(s):  
Frits van Rhee ◽  
Vanessa Bolejack ◽  
Klaus Hollmig ◽  
Mauricio Pineda-Roman ◽  
Elias Anaissie ◽  
...  

Abstract 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 μM (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.


Pathology ◽  
2009 ◽  
Vol 41 ◽  
pp. 76
Author(s):  
Nani Nordin ◽  
P. Sthaneshwar ◽  
Veera S. Nadarajan

2020 ◽  
Vol 4 (22) ◽  
pp. 5836-5845
Author(s):  
Ritika Rana ◽  
Paul Cockwell ◽  
Mark Drayson ◽  
Mark Cook ◽  
Guy Pratt ◽  
...  

Abstract Renal injury is a common complication of multiple myeloma (MM) and is associated with adverse outcome. Despite this, the natural history of renal injury in patients with MM remains uncertain especially in the context of intensive therapy and novel therapies. To address the lack of data, we evaluated the renal function of 2334 patients from the UK National Cancer Research Institute Myeloma XI trial at baseline and at 12 months to assess renal function over time and the factors associated with change. Patients who had severe acute kidney injury or a requirement for dialysis were excluded. At 12 months of the 1450 evaluable patients planned for autologous transplantation; 204 (14%) patients had a decline in estimated glomerular filtration rate (eGFR) ≥25% from baseline, 341 (23.5%) had an improvement and 905 (62%) had no significant change in eGFR. Renal outcome at 12 months for the 884 evaluable patients who were not planned for transplant was similar. Improved renal function was more likely if patients were &lt;70 years old, male, had an average eGFR &lt;60 mL per minute per 1.73 m2 and a higher baseline free light chain level &gt;1000 mg/L, and/or a free light chain response of &gt;90%. It did not correlate with monoclonal–protein response, transplantation, or use of a bortezomib-based regimen. We show that with current therapies the proportion of patients who have a significant decline in renal function in the first 12 months is small. The greatest relative improvement in eGFR is seen in patients with high free light chain at baseline and a high light chain response. This trial was registered at http://www.isrctn.com as #49407852.


Sign in / Sign up

Export Citation Format

Share Document