Relationship between elevated immunoglobulin free light chain and the presence of IgH translocations in multiple myeloma

Kumar, Shaji; Zhang, L; Dispenzieri, Angela; Wier, Scott Van; Katzmann, Jerry A.; Snyder, Melissa R.; Blood, Emily A.; DeGoey, Roberta; Henderson, Kim; Kyle, Robert A.; Bradwell, Arthur R.; Greipp, P. R.; Rajkumar, S. Vincent; Fonseca, Rafaël

doi:10.1038/leu.2010.128

Cited by 37 publications

(27 citation statements)

References 42 publications

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“…27 However, they also found that the negative prognostic effect of very abnormal FLC levels was independent of the translocation abnormality [t(4;14) and t(14;16)]. 27 In our data set, IgH translocations were only available in 277 patients (53.1% of relapsed population) and, therefore, fluorescence in situ hybridization data were not included in the multivariate analysis.…”

Section: Discussionmentioning

confidence: 98%

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

Brioli

Giles

Pawlyn

et al. 2014

Blood

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Key Points• The type of antibody secreted at relapse can serve as a marker of clonal heterogeneity.• It is important to monitor for serum FLC in the suspicion of clinical relapse to ensure that FLC relapse is not missed.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. (Blood. 2014;123(22):3414-3419)

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Section: Discussionmentioning

confidence: 98%

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

Brioli

Giles

Pawlyn

et al. 2014

Blood

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“…5 We identified a significant suppression of rFLC in cases with gain 1q21 for IgG MM. M-protein levels in IgG MM were higher compared with those in IgA MM cases.…”

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confidence: 86%

“…[2][3][4] One study showed that cases with IgH translocations had higher FLC levels and abnormal FLC ratio. 5 Recently, prognostic significance was shown for isotype matched Ig ratios (e.g. IgGκ/IgGλ).…”

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confidence: 99%

Cytogenetic aberrations in multiple myeloma are associated with shifts in serum immunoglobulin isotypes distribution and levels

et al. 2018

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aberrations in multiple myeloma are associated with shifts in serum immunoglobulin isotypes distribution and levels. Haematologica. 2018; 103:xxx doi:10.3324/haematol.2017.184226 Publisher's Disclaimer. As yet, the possible impact of CAs on Ig and FLC subtypes and their levels is poorly studied in MM. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have completed a regular peer review and have been accepted for publication. E-publishing of this PDF file has been approved by the authors. After having E-published Ahead of Print, manuscripts will then undergo technical and English editing, typesetting, proof correction and be presented for the authors' final approval; the final version of the manuscript will then appear in print on a regular issue of the journal. All legal disclaimers that apply to the journal also pertain to this production process.The hypothesis is that CAs are associated with the involved Ig isotypes in MM. We carried out a systematic analysis of Ig and FLC subtypes and their serum levels in relation with common CAs using data on 523 patients recruited in German-Speaking Myeloma Multicenter Group (GMMG)-MM5 trial. 9, 10 For purpose of replication, an independent cohort of 325 cases from GMMG-HD4 trial was obtained. 11, 12Blood samples were collected prior to treatment initiation in the above trials, coordinated by ). The difference remained consistent, but smaller and of borderline significant in the GMMG-HD4 cohort (44.9 g/l vs 39.1 g/l; p=0.06).The individual FLCκ levels were outside the reference range for 80% of cases, and for 63% cases exceeded upper limit (>19.4 mg/l; Online Supplementary Table S4). FLCλ levels were outside the reference range for 63% cases, and for 31% cases surpassed upper limit (>26.3 mg/l). OnlineSupplementary In a previous study, higher rFLC was found in patients with t(14;16) or del(13). 5 We identified a significant suppression of rFLC in cases with gain 1q21 for IgG MM. M-protein levels in IgG MM were higher compared with those in IgA MM cases. This might be expected as IgG is the principal isotype in the blood and extracellular fluid whereas IgA is the principal isotype in secretions of mucus epithelium of the intestinal and respiratory tracts. The observation that M-protein levels were higher in any IgH translocation group compared with the hyperdiploidy group can possibly be attributed to the active production of M-protein in actively proliferating plasma cells driven by the translocated cyclin D genes. 15 Patients lacking hyperdiploidy had higher M-protein level compared with hyperdiploidy patients, although this difference was statistically significant for IgA MM alone.In summary, our study provides strong evidence for a complex modifying role of at least two CA types on immunophenotype. We showed further that serum Ig and FLC levels were influenced by several CA types. Our study thus sheds new light on the role of CA a...

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“…2,6 However, no light chain excess has been reported in either t(11;14) AL amyloidosis or in t(11;14) MM.…”

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confidence: 99%

Genome-wide association study of clinical parameters in immunoglobulin light chain amyloidosis in three patient cohorts

et al. 2017

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Relationship between elevated immunoglobulin free light chain and the presence of IgH translocations in multiple myeloma

Cited by 37 publications

References 42 publications

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

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

Cytogenetic aberrations in multiple myeloma are associated with shifts in serum immunoglobulin isotypes distribution and levels

Genome-wide association study of clinical parameters in immunoglobulin light chain amyloidosis in three patient cohorts

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