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, Maurizio Zangari, Guido Tricot, Abid Mohiuddin, Yazan Alsayed, Gail Woods, John Crowley, Bart Barlogie

Research output: Contribution to journalArticle

141 Scopus citations

Abstract

Serum-free light chain (SFLC) levels are useful for diagnosing nonsecretory myeloma and monitoring response in lightchain-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 toptertile 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.

Original languageEnglish (US)
Pages (from-to)827-832
Number of pages6
JournalBlood
Volume110
Issue number3
DOIs
StatePublished - Aug 1 2007

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Van Rhee, F., Bolejack, V., Hollmig, K., Pineda-Roman, M., Anaissie, E., Epstein, J., Shaughnessy, J. D., Zangari, M., Tricot, G., Mohiuddin, A., Alsayed, Y., Woods, G., Crowley, J., & Barlogie, B. (2007). High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis. Blood, 110(3), 827-832. https://doi.org/10.1182/blood-2007-01-067728