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Blood, 1 August 2007, Vol. 110, No. 3, pp. 827-832.
Prepublished online as a Blood First Edition Paper on April 6, 2007April 30, 2007; DOI 10.1182/blood-2007-01-067728.
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Submitted January 11, 2007
Accepted February 28, 2007
High serum free-light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis
Frits van Rhee, Vanessa Bolejack, Klaus Hollmig, Mauricio Pineda-Roman, Elias Anaissie, Joshua Epstein, John D Shaughnessy Jr, Maurizio Zangari, Guido Tricot, Abid Mohiuddin, Yazan Alsayed, Gail Woods, John Crowley, and Bart Barlogie*
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR
Cancer Research and Biostatistics, CRAB, Seattle, WA
* Corresponding author; email: barlogiebart{at}uams.edu.
Serum free-light chain (SFLC) levels are useful for diagnosing non-secretory myeloma and monitoring response in light-chain only disease, especially in the presence of renal failure. As part of a tandem autotransplant trial for newly diagnosed multiple myeloma, SFLC levels were measured at baseline, within 7 days of starting the first cycle and both prior to the second induction cycle and the first transplant. SFLC baseline levels >75mg/dL (top-tertile) identified 33% of 301 patients with higher near-complete response rate (n-CR) to induction therapy (37% v 20%, p=0.002) yet inferior 24-mo overall survival (OS: 76% v 91%, p<0.001) and event-free survival (EFS:73% v 90%, p<0.001), retaining independent prognostic significance for both EFS (HR=2.40, p=0.008) and OS (HR=2.43, p=0.016). Baseline SFLC >75mg/dL was associated with light-chain only secretion (p<.001), creatinine >=2mg/dL (p<.001), beta-2-microglobulin >=3.5mg/L (p<.001), lactate dehydrogenase >=190U/L (p<.001) and bone marrow plasmacytosis >30% (p=.003). Additional independent adverse implications were conferred by top-tertile SFLC reductions prior to cycle 2 (OS: HR=2.97, p=0.003; EFS: HR=2.56, p=0.003) and pre-transplant (OS: HR=3.31, p=0.001; EFS: HR=2.65, p=0.003). 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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