Serum free light chains, not urine specimens, should be used to evaluate response in light-chain multiple myeloma

Charlotte Fontan (1) , Mourad Tiab (2) , Pascal Godmer (3) , Odile Luycx , Olivier Allangba , Jean-Michel Pignon (4) , Jean-Gabriel Fuzibet (5) , Laurence Legros , Anne Marie Stoppa (6) , Mamoun Dib , Brigitte Pegourie , Frederique Orsini-Piocelle , Lionel Karlin (7) , Bertrand Arnulf (8) , Murielle Roussel (9) , Laurent Garderet (10) , Mohamad Mohty (10) , Nathalie Meuleman , Chantal Doyen , Pascal Lenain (11) , Margaret Macro (12) , Xavier Leleu , Thierry Facon (13) , Philippe Moreau (14) , Michel Attal (15, 1) , Hervé Avet-Loiseau (1) , Thomas Dejoie (16) , Jill Corre (1) , Hélène Caillon (16) , Cyrille Hulin , Aurore Perrot (17) , Denis Caillot (18, 19, 20) , Eileen Boyle (21) , Marie-Lorraine Chrétien (18, 19, 20) , Jean Fontan (22) , Karim Belhadj (23) , Sabine Bréchignac (24) , Olivier Decaux (25) , Laurent Voillat (26) , Philippe Rodon , Olivier Fitoussi (27) , Carla Araujo , Lotfi Benboubker (28)

1 CRCT - Centre de Recherches en Cancérologie de Toulouse
2 Hôpital Général de La Roche sur Yon
3 CHBA - Centre hospitalier Bretagne Atlantique (Morbihan)
4 Centre Hospitalier Dunkerque
5 Département Universitaire Nice
6 Institut Paoli-Calmettes
7 Hopital universitaire de Lyon
8 Service d'hématologie biologique
9 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
10 CHU Saint-Antoine [AP-HP]
11 Service d'Hématologie
12 Hôpital Universitaire de Caen
13 Hôpital Claude Huriez [Lille]
14 IMN - Institut des Matériaux Jean Rouxel
15 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
16 Laboratoire de Biochimie [Nantes]
17 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
18 LNC - Lipides - Nutrition - Cancer (U866)
19 LabEx LipSTIC - Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer
20 Service d'Hématologie Clinique (CHU de Dijon)
21 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]
22 Service d'hématologie
23 Service d'Hématologie Biologique
24 Hôpital Universitaire de Bobigny
25 IGDR - Institut de Génétique et Développement de Rennes
26 Centre Hospitalier Chalon-sur-Saône William Morey
27 Polyclinique Bordeaux Nord Aquitaine
28 Hôpital Universitaire de Tours

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.

Domains: Life Sciences [q-bio]; Genetics

Charlotte Fontan, Mourad Tiab, Pascal Godmer, Odile Luycx, Olivier Allangba, et al.. Serum free light chains, not urine specimens, should be used to evaluate response in light-chain multiple myeloma. Blood, 2016, 128 (25), pp.2941-2948. ⟨10.1182/blood-2016-07-726778⟩. ⟨hal-01439375⟩