Dejoie Thomas, Corre Jill, Caillon Helene, Hulin Cyrille, Perrot Aurore, Caillot Denis, Boyle Eileen, Chretien Marie-Lorraine, Fontan Jean, Belhadj Karim, Brechignac Sabine, Decaux Olivier, Voillat Laurent, Rodon Philippe, Fitoussi Olivier, Araujo Carla, Benboubker Lotfi, Fontan Charlotte, Tiab Mourad, Godmer Pascal, Luycx Odile, Allangba Olivier, Pignon Jean-Michel, Fuzibet Jean-Gabriel, Legros Laurence, Stoppa Anne Marie, Dib Mamoun, Pegourie Brigitte, Orsini-Piocelle Frederique, Karlin Lionel, Arnulf Bertrand, Roussel Murielle, Garderet Laurent, Mohty Mohamad, Meuleman Nathalie, Doyen Chantal, Lenain Pascal, Macro Margaret, Leleu Xavier, Facon Thierry, Moreau Philippe, Attal Michel, Avet-Loiseau Herve
Biochemistry Laboratory and Hematology Department, Centre Hospitalier Universitaire (CHU), Nantes, France.
Institut Universitaire du Cancer, CHU, Centre de Recherche en Cancérologie de Toulouse, INSERM 1037, Toulouse, France.
Blood. 2016 Dec 22;128(25):2941-2948. doi: 10.1182/blood-2016-07-726778. Epub 2016 Oct 11.
Guidelines for monitoring multiple myeloma (MM) patients expressing light chains only (light-chain MM [LCMM]) rely on measurements of monoclonal protein in urine. Alternatively, serum free light chain (sFLC) measurements have better sensitivity over urine methods, however, demonstration that improved sensitivity provides any clinical benefit is lacking. Here, we compared performance of serum and urine measurements in 113 (72κ, 41λ) newly diagnosed LCMM patients enrolled in the Intergroupe Francophone du Myélome (IFM) 2009 trial. All diagnostic samples (100%) had an abnormal κ:λ sFLC ratio, and involved (monoclonal) FLC (iFLC) expressed at levels deemed measurable for monitoring (≥100 mg/L). By contrast, only 64% patients had measurable levels of monoclonal protein (≥200 mg per 24 hours) in urine protein electrophoresis (UPEP). After 1 and 3 treatment cycles, iFLC remained elevated in 71% and 46% of patients, respectively, whereas UPEP reported a positive result in 37% and 18%; all of the patients with positive UPEP at cycle 3 also had elevated iFLC levels. Importantly, elevated iFLC or an abnormal κ:λ sFLC ratio after 3 treatment cycles associated with poorer progression-free survival (P = .006 and P < .0001, respectively), whereas positive UPEP or urine immunofixation electrophoresis (uIFE) did not. In addition, patients with an abnormal κ:λ sFLC ratio had poorer overall survival (P = .022). Finally, early normalization of κ:λ sFLC ratio but not negative uIFE predicted achieving negative minimal residual disease, as determined by flow cytometry, after consolidation therapy (100% positive predictive value). We conclude that improved sensitivity and prognostic value of serum over urine measurements provide a strong basis for recommending the former for monitoring LCMM patients.
仅表达轻链的多发性骨髓瘤（MM）患者（轻链型MM [LCMM]）的监测指南依赖于尿中单克隆蛋白的检测。另外，血清游离轻链（sFLC）检测比尿液检测方法具有更高的灵敏度，然而，目前尚缺乏证据表明更高的灵敏度能带来任何临床益处。在此，我们比较了113例（κ型72例，λ型41例）新诊断的LCMM患者血清和尿液检测的性能，这些患者均参加了法语国家骨髓瘤研究组（IFM）2009试验。所有诊断样本（100%）的κ:λ sFLC比值均异常，且受累（单克隆）FLC（iFLC）表达水平达到可用于监测的可测水平（≥100 mg/L）。相比之下，仅64%的患者在尿蛋白电泳（UPEP）中检测到可测水平的单克隆蛋白（≥200 mg/24小时）。在1个和3个治疗周期后，分别有71%和46%的患者iFLC仍处于升高水平，而UPEP报告阳性结果的患者分别为37%和18%；在第3周期UPEP呈阳性的所有患者iFLC水平也均升高。重要的是，3个治疗周期后iFLC升高或κ:λ sFLC比值异常与无进展生存期较差相关（分别为P = 0.006和P < 0.0001），而UPEP或尿免疫固定电泳（uIFE）呈阳性则无此关联。此外，κ:λ sFLC比值异常的患者总生存期较差（P = 0.022）。最后，κ:λ sFLC比值早期恢复正常而非uIFE阴性可预测巩固治疗后通过流式细胞术检测达到微小残留病阴性（阳性预测值为100%）。我们得出结论，血清检测比尿液检测具有更高的灵敏度和预后价值，这为推荐前者用于监测LCMM患者提供了有力依据。
