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

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.本研究针对遵循GEM2005MENOS65、GEM2005MAS65及GEM2010MAS65 PETHEMA/GEM三项III期临床试验方案治疗的多发性骨髓瘤（multiple myeloma）患者，探讨了血清游离轻链（serum free light chains, sFLC）与血清重轻链（serum heavy-light chains, sHLC）的预后影响及临床应用价值。 本研究对诊断时采集的血清样本进行回顾性分析：其中用于sFLC检测的样本共623份（n=623），用于sHLC检测的样本共183份（n=183）。经诱导治疗或自体造血干细胞移植（autologous transplantation）后，可用于sFLC检测的样本为309份，可用于sHLC检测的样本为89份。 诊断时，血清游离轻链比值（sFLCr）显著异常（highly abnormal, HA）（阈值>32）与更高的疾病进展风险无显著关联。治疗后，受累sFLC水平持续>100 mg/L提示患者总生存期（overall survival, OS）更差（P=0.03）、无进展生存期（progression-free survival, PFS）更短（P=0.007）。在达到完全缓解（complete response）的患者中，sFLCr恢复正常并不一定代表获得更高质量的临床应答。 本研究针对IgG型和IgA型多发性骨髓瘤开展了sHLC相关检测。血清重轻链的绝对数值与血清蛋白电泳（serum protein electrophoresis）检测得到的单克隆蛋白水平呈显著相关。诊断时，血清重轻链比值显著异常（HA-sHLCr，阈值>73）与更高的疾病进展风险相关（P=0.006）。此外，治疗后受累sHLC水平>5 g/L与更短的生存期相关（OS：P=0.001；PFS：P=0.018）。 综上，诊断时的血清重轻链比值显著异常具备预后评估潜力；治疗后受累sFLC>100 mg/L、受累sHLC>5 g/L的绝对数值水平同样具备预后评估价值。