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

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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

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Multiple Myeloma
Light
Serum
Therapeutics
Transplantation
beta 2-Microglobulin
Survival
Autologous Transplantation
L-Lactate Dehydrogenase
Creatinine
Bone
Disease-Free Survival
Renal Insufficiency
Blood Proteins
Bone Marrow
Urine
Monitoring
Proteins

ASJC Scopus subject areas

  • Hematology

Cite this

Van Rhee, F., Bolejack, V., Hollmig, K., Pineda-Roman, M., Anaissie, E., Epstein, 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

High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis. / Van Rhee, Frits; Bolejack, Vanessa; Hollmig, Klaus; Pineda-Roman, Mauricio; Anaissie, Elias; Epstein, Joshua; Shaughnessy, John D.; Zangari, Maurizio; Tricot, Guido; Mohiuddin, Abid; Alsayed, Yazan; Woods, Gail; Crowley, John; Barlogie, Bart.

In: Blood, Vol. 110, No. 3, 01.08.2007, p. 827-832.

Research output: Contribution to journalArticle

Van Rhee, F, Bolejack, V, Hollmig, K, Pineda-Roman, M, Anaissie, E, Epstein, J, Shaughnessy, JD, 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, vol. 110, no. 3, pp. 827-832. https://doi.org/10.1182/blood-2007-01-067728
Van Rhee, Frits ; Bolejack, Vanessa ; Hollmig, Klaus ; Pineda-Roman, Mauricio ; Anaissie, Elias ; Epstein, Joshua ; Shaughnessy, John D. ; Zangari, Maurizio ; Tricot, Guido ; Mohiuddin, Abid ; Alsayed, Yazan ; Woods, Gail ; Crowley, John ; Barlogie, Bart. / High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis. In: Blood. 2007 ; Vol. 110, No. 3. pp. 827-832.
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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.",
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AU - Pineda-Roman, Mauricio

AU - Anaissie, Elias

AU - Epstein, Joshua

AU - Shaughnessy, John D.

AU - Zangari, Maurizio

AU - Tricot, Guido

AU - Mohiuddin, Abid

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