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
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) (<0.03 or >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 (<0.29 or >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.