title: Serum free light chains, not urine specimens, should be used to evaluate response in light-chain multiple myeloma.
abstract: 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.
authors.affiliation: Biochemistry Laboratory and Hematology Department, Centre Hospitalier Universitaire (CHU), Nantes, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dejoie
authors.affiliation: Institut Universitaire du Cancer, CHU, Centre de Recherche en Cancérologie de Toulouse, INSERM 1037, Toulouse, France.
authors.forename: Jill
authors.initials: J
authors.lastname: Corre
authors.affiliation: Biochemistry Laboratory and Hematology Department, Centre Hospitalier Universitaire (CHU), Nantes, France.
authors.forename: Helene
authors.initials: H
authors.lastname: Caillon
authors.affiliation: Hematology Department, CHU, Bordeaux, France.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Hulin
authors.affiliation: Hematology Department, CHU, Nancy, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Perrot
authors.affiliation: Hematology Department, CHU, Dijon, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Caillot
authors.affiliation: Hematology Department, CHU, Lille, France.
authors.forename: Eileen
authors.initials: E
authors.lastname: Boyle
authors.affiliation: Hematology Department, CHU, Dijon, France.
authors.forename: Marie-Lorraine
authors.initials: ML
authors.lastname: Chretien
authors.affiliation: Hematology Department, CHU, Besancon, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Fontan
authors.affiliation: Hematology Department, CHU, Creteil, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Belhadj
authors.affiliation: Hematology Department, CHU, Bobigny, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Brechignac
authors.affiliation: Internal Medicine, CHU, Rennes, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Decaux
authors.affiliation: Centre Hospitalier William Morey, Departmental Hospital, Chalon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Voillat
authors.affiliation: Clinical Research Unit, Centre Hospitalier de Périgueux, Departmental Hospital, Perigueux, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rodon
authors.affiliation: Hematology Department, Polyclinique Bordeaux-Nord, Bordeaux, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Fitoussi
authors.affiliation: Centre Hospitalier Departemental, Bayonne, France.
authors.forename: Carla
authors.initials: C
authors.lastname: Araujo
authors.affiliation: Hôpital Bretonneau, CHU, Tours, France.
authors.forename: Lotfi
authors.initials: L
authors.lastname: Benboubker
authors.affiliation: Institut Universitaire du Cancer, CHU, Centre de Recherche en Cancérologie de Toulouse, INSERM 1037, Toulouse, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Fontan
authors.affiliation: Centre Hospitalier Departemental, La Roche sur Yon, La Roche/Yon, France.
authors.forename: Mourad
authors.initials: M
authors.lastname: Tiab
authors.affiliation: Centre Hospitalier Departemental, Vannes, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Godmer
authors.affiliation: Centre Hospitalier Departemental, Lorient, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Luycx
authors.affiliation: Centre Hospitalier Departemental, Saint-Brieuc, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Allangba
authors.affiliation: Centre Hospitalier Departemental, Dunkerque, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pignon
authors.affiliation: Internal Medicine, CHU, Nice, France.
authors.forename: Jean-Gabriel
authors.initials: JG
authors.lastname: Fuzibet
authors.affiliation: Internal Medicine, CHU, Nice, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Legros
authors.affiliation: Hematology Department, Institut Paoli Calmette, Marseille, France.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Stoppa
authors.affiliation: Hematology Department, CHU, Angers, France.
authors.forename: Mamoun
authors.initials: M
authors.lastname: Dib
authors.affiliation: Hematology Department, CHU, Grenoble, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Pegourie
authors.affiliation: Hematology Department, Centre Hospitalier Departemental, Annecy, France.
authors.forename: Frederique
authors.initials: F
authors.lastname: Orsini-Piocelle
authors.affiliation: Hematology Department, CHU, Lyon, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Karlin
authors.affiliation: Immunopathology Service, Saint-Louis University Hospital, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Arnulf
authors.affiliation: Institut Universitaire du Cancer, CHU, Centre de Recherche en Cancérologie de Toulouse, INSERM 1037, Toulouse, France.
authors.forename: Murielle
authors.initials: M
authors.lastname: Roussel
authors.affiliation: Hematology Department, Saint-Antoine University Hospital, Paris, France.
authors.forename: Laurent
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authors.lastname: Garderet
authors.affiliation: Hematology Department, Saint-Antoine University Hospital, Paris, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.affiliation: Department of Clinical and Experimental Hematology, Jules Bordet Institute, Brussels, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Meuleman
authors.affiliation: Department of Clinical and Experimental Research, Clinique Universitaire Mont-Godinne, Yvoir, Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Doyen
authors.affiliation: Hematology Department, Centre Henri Becquerel, Rouen, France.
authors.forename: Pascal
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authors.lastname: Lenain
authors.affiliation: Hematology Department, CHU, Caen, France; and.
authors.forename: Margaret
authors.initials: M
authors.lastname: Macro
authors.affiliation: Hematology Department, CHU, Poitiers, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
authors.affiliation: Hematology Department, CHU, Lille, France.
authors.forename: Thierry
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authors.lastname: Facon
authors.affiliation: Biochemistry Laboratory and Hematology Department, Centre Hospitalier Universitaire (CHU), Nantes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Institut Universitaire du Cancer, CHU, Centre de Recherche en Cancérologie de Toulouse, INSERM 1037, Toulouse, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Attal
authors.affiliation: Institut Universitaire du Cancer, CHU, Centre de Recherche en Cancérologie de Toulouse, INSERM 1037, Toulouse, France.
authors.forename: Herve
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authors.lastname: Avet-Loiseau
mesh_terms: D000328:Adult; D060830:Consolidation Chemotherapy; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood* / Q000652:urine*; D060828:Induction Chemotherapy; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000188:drug therapy / Q000652:urine*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012015:Reference Standards; D016019:Survival Analysis
chemical_list: D007147:Immunoglobulin Light Chains