PLoS ONE (Jan 2018)

Prognostic utility of serum free light chain ratios and heavy-light chain ratios in multiple myeloma in three PETHEMA/GEM phase III clinical trials.

  • Lucia Lopez-Anglada,
  • Cecilia Cueto-Felgueroso,
  • Laura Rosiñol,
  • Albert Oriol,
  • Ana Isabel Teruel,
  • Ana Lopez de la Guia,
  • Enrique Bengoechea,
  • Luis Palomera,
  • Felipe de Arriba,
  • Jose Mariano Hernandez,
  • Miquel Granell,
  • Francisco Javier Peñalver,
  • Ramon Garcia-Sanz,
  • Juan Besalduch,
  • Yolanda Gonzalez,
  • Rafael Benigno Martinez,
  • Miguel Teodoro Hernandez,
  • Norma C Gutierrez,
  • Paloma Puerta,
  • Antonio Valeri,
  • Bruno Paiva,
  • Joan Blade,
  • Maria-Victoria Mateos,
  • Jesus San Miguel,
  • Juan Jose Lahuerta,
  • Joaquin Martinez-Lopez,
  • GEM (Grupo Español de MM)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) Cooperative Study Group

DOI
https://doi.org/10.1371/journal.pone.0203392
Journal volume & issue
Vol. 13, no. 9
p. e0203392

Abstract

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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) (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 (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.