Deeper responses are associated with improved survival in patients being treated for myeloma. However, the sensitivity of the current blood-based assays is limited. Historical studies suggested that normalisation of the serum free light chain (FLC) ratio in patients who were negative by immunofixation electrophoresis (IFE) was associated with improved outcomes. However, recently this has been called into question. Mass spectrometry (MS)-based FLC assessments may offer a superior methodology for the detection of monoclonal FLC due to greater sensitivity. To test this hypothesis, all available samples from patients who were IFE negative after treatment with carfilzomib and lenalidomide-based induction and autologous stem cell transplantation (ASCT) in the Myeloma XI trial underwent FLC-MS testing. FLC-MS response assessments from post-induction, day+100 post-ASCT and six months post-maintenance randomisation were compared to serum FLC assay results. Almost 40% of patients had discordant results and 28.7% of patients with a normal FLC ratio had residual monoclonal FLC detectable by FLC-MS. FLC-MS positivity was associated with reduced progression-free survival (PFS) but an abnormal FLC ratio was not. This study demonstrates that FLC-MS provides a superior methodology for the detection of residual monoclonal FLC with FLC-MS positivity identifying IFE-negative patients who are at higher risk of early progression.
在多发性骨髓瘤治疗中，更深度的治疗反应与患者生存期的改善相关。然而，当前基于血液检测方法的敏感性有限。既往研究提示，经免疫固定电泳检测呈阴性的患者若其血清游离轻链比值恢复正常，往往预示着更好的临床结局。但近期这一观点受到质疑。基于质谱分析的游离轻链检测方法因其更高的灵敏度，可能为单克隆游离轻链的检测提供更优方案。为验证该假设，本研究对骨髓瘤XI试验中所有经卡非佐米和来那度胺为基础诱导治疗及自体干细胞移植后免疫固定电泳转阴的患者样本进行质谱法游离轻链检测。将诱导治疗后、移植后100天及维持治疗随机分组后6个月的质谱法游离轻链评估结果与血清游离轻链检测结果进行对比。结果显示，近40%患者的两类检测结果不一致，且在血清游离轻链比值正常的患者中，28.7%可通过质谱法检测到残留单克隆游离轻链。质谱法游离轻链阳性与无进展生存期缩短相关，而异常的血清游离轻链比值则未显示此关联。本研究表明，质谱法游离轻链检测为残留单克隆游离轻链的检测提供了更优方法，其阳性结果能识别出免疫固定电泳阴性但早期进展风险更高的患者群体。
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