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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 
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.
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Submitted on : Wednesday, January 18, 2017 - 3:34:15 PM
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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, American Society of Hematology, 2016, 128 (25), pp.2941-2948. ⟨10.1182/blood-2016-07-726778⟩. ⟨hal-01439375⟩



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