title: Serum free immunoglobulin light chain evaluation as a marker of impact from intraclonal heterogeneity on myeloma outcome.
abstract: Intraclonal heterogeneity was recently described in multiple myeloma (MM), but its full impact on disease progression and relapse has not been entirely explored. The immunoglobulin type produced by myeloma cells provides an excellent marker to follow changes in clonal substructure over time. We have prospectively evaluated serial paraprotein and serum free light chain (FLC) measurements and found that 258 of 520 and 54 of 520 patients who presented with a whole paraprotein relapsed with paraprotein only (PO) and "FLC escape," respectively. The median overall survival of PO patients was longer, when compared with patients whose relapse manifested as an increase in FLC both alone and with a whole paraprotein, as a result of a significantly shorter survival from relapse of the latter groups. These observations fit a model in which 1 clone is able to produce a complete antibody, whereas the other secretes only FLC; the type of relapse represents the outgrowth of different clones, some of which are more resistant to therapy. To our knowledge, this is the largest series describing patients who have relapsed with FLC escape and highlights the importance of monitoring FLC when there is a suspicion of clinical relapse. This study was registered at www.isrctn.org as ISRCTN68454111.
authors.affiliation: Myeloma Research Centre, Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom; Istituto di Ematologia Seràgnoli, Università degli Studi di Bologna, Policlinico S. Orsola-Malpighi, Bologna, Italy;
authors.forename: Annamaria
authors.initials: A
authors.lastname: Brioli
authors.affiliation: Clinical Immunology Service, University of Birmingham Medical School, Birmingham, United Kingdom;
authors.forename: Hannah
authors.initials: H
authors.lastname: Giles
authors.affiliation: Myeloma Research Centre, Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom;
authors.forename: Charlotte
authors.initials: C
authors.lastname: Pawlyn
authors.affiliation: Clinical Immunology Service, University of Birmingham Medical School, Birmingham, United Kingdom;
authors.forename: John P
authors.initials: JP
authors.lastname: Campbell
authors.affiliation: Myeloma Research Centre, Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom;
authors.forename: Martin F
authors.initials: MF
authors.lastname: Kaiser
authors.affiliation: Myeloma Research Centre, Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom;
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Melchor
authors.affiliation: Haematology Department, University of Newcastle, Newcastle-upon-Tyne, United Kingdom;
authors.forename: Graham H
authors.initials: GH
authors.lastname: Jackson
authors.affiliation: Clinical Trials Research Unit, University of Leeds, Leeds, United Kingdom; and.
authors.forename: Walter M
authors.initials: WM
authors.lastname: Gregory
authors.affiliation: St. James's University Hospital, Leeds, United Kingdom.
authors.forename: Roger G
authors.initials: RG
authors.lastname: Owen
authors.affiliation: Clinical Trials Research Unit, University of Leeds, Leeds, United Kingdom; and.
authors.forename: J Anthony
authors.initials: JA
authors.lastname: Child
authors.affiliation: Myeloma Research Centre, Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom;
authors.forename: Faith E
authors.initials: FE
authors.lastname: Davies
authors.affiliation: Istituto di Ematologia Seràgnoli, Università degli Studi di Bologna, Policlinico S. Orsola-Malpighi, Bologna, Italy;
authors.forename: Michele
authors.initials: M
authors.lastname: Cavo
authors.affiliation: Clinical Immunology Service, University of Birmingham Medical School, Birmingham, United Kingdom;
authors.forename: Mark T
authors.initials: MT
authors.lastname: Drayson
authors.affiliation: Myeloma Research Centre, Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom;
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Morgan
mesh_terms: D015415:Biomarkers / Q000097:blood; D060965:Clonal Evolution; D005500:Follow-Up Studies; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007147:Immunoglobulin Light Chains / Q000097:blood*; D008954:Models, Biological; D009101:Multiple Myeloma / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D010266:Paraproteins; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007147:Immunoglobulin Light Chains; D010266:Paraproteins