Journal
BLOOD
Volume 123, Issue 22, Pages 3414-3419Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2013-12-542662
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Funding
- Myeloma United Kingdom
- National Institute for Health Research Biomedical Research Centre at the Royal Marsden Hospital
- National Cancer Research Institute Haemato-Oncology subgroup
- Medical Research Council [MR/L01629X/1] Funding Source: researchfish
- National Institute for Health Research [ACF-2013-09-002] Funding Source: researchfish
- MRC [MR/L01629X/1] Funding Source: UKRI
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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 www.isrctn.org as ISRCTN68454111.
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