Abstract
Brioli A, Giles H, Pawlyn C, et al.
Blood 2014; 123: 3414–3419.
In multiple myeloma (MM), an abnormal plasma cell clone secretes immunoglobulins, free light chains (FLCs), or both. Despite its ‘monoclonal’ nature, genetic and phenotypic variation within clones in MM is now recognised. Progression of such intraclonal heterogeneity (manifest as changes in immunoglobulin type over time) is the subject of this study.
Data from 520 patients from the Myeloma IX trial who suffered relapse were analysed. Relapse was categorised as paraprotein only (49.6%), FLC and paraprotein (35.2%) and FLC only (10.4%). Patients whose relapse included increased FLC had decreased overall survival time by ∼13 months when compared with paraprotein only relapse (P = 0.015), with the discrepancy mainly due to survival post relapse. The difference in survival time was suggested to be due to intraclonal heterogeneity, with greater resistance of FLC subclones to chemotherapy. A mechanism however was not suggested for this differing subclonal response.
The authors suggest FLC monitoring in MM to assess intraclonal heterogeneity, and to aid detection of relapse. However, as many patients with FLC relapse also had elevated FLC at diagnosis (an adverse prognostic sign), it is not yet clear if FLC relapse provides independent prognostic information.