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Serum free immunoglobulin light chain evaluation as a marker of impact from intraclonal heterogeneity on myeloma outcome

Lookup NU author(s): Professor Graham Jackson


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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 as ISRCTN68454111.

Publication metadata

Author(s): Brioli A, Giles H, Pawlyn C, Campbell JP, Kaiser MF, Melchor L, Jackson GH, Gregory WM, Owen RG, Child JA, Davies FE, Cavo M, Drayson MT, Morgan GJ

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2014

Volume: 123

Issue: 22

Pages: 3414-3419

Print publication date: 29/05/2014

Online publication date: 14/04/2014

Acceptance date: 31/03/2014

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

Publisher: American Society of Hematology


DOI: 10.1182/blood-2013-12-542662


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