Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma
A markedly elevated serum free light chain (FLC) ratio may serve as a biomarker for malignant transformation in high-risk smoldering multiple myeloma (SMM) and identify patients who are at imminent risk of progression. We retrospectively studied the predictive value of the serum (FLC) assay in 586 p...
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description | A markedly elevated serum free light chain (FLC) ratio may serve as a biomarker for malignant transformation in high-risk smoldering multiple myeloma (SMM) and identify patients who are at imminent risk of progression. We retrospectively studied the predictive value of the serum (FLC) assay in 586 patients with SMM diagnosed between 1970 to 2010. A serum involved/uninvolved FLC ratio ⩾100 was used to define high-risk SMM, which included 15% (
n
=90) of the total cohort. Receiver operating characteristics analysis determined the optimal FLC ratio cut-point to predict progression to symptomatic multiple myeloma (MM) within 2 years of diagnosis, which resulted in a specificity of 97% and sensitivity of 16%. Fifty-six percent of patients developed progressive disease during median follow-up of 52 months, but this increased to 98% in the subgroup of patients with FLC ratio ⩾100. The median time to progression in the FLC ratio ⩾100 group was 15 months versus 55 months in the FLC |
doi_str_mv | 10.1038/leu.2012.296 |
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n
=90) of the total cohort. Receiver operating characteristics analysis determined the optimal FLC ratio cut-point to predict progression to symptomatic multiple myeloma (MM) within 2 years of diagnosis, which resulted in a specificity of 97% and sensitivity of 16%. Fifty-six percent of patients developed progressive disease during median follow-up of 52 months, but this increased to 98% in the subgroup of patients with FLC ratio ⩾100. The median time to progression in the FLC ratio ⩾100 group was 15 months versus 55 months in the FLC <100 group (
P
<0.0001). The risk of progression to MM within the first 2 years in patients with an FLC ratio ⩾100 was 72%; the risk of progression to MM or light chain amyloidosis in 2 years was 79%. We conclude that a high FLC ratio ⩾100 is a predictor of imminent progression in SMM, and such patients may be considered candidates for early treatment intervention.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/leu.2012.296</identifier><identifier>PMID: 23183428</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/699/67/1857 ; 692/699/67/1990/804 ; 692/700/1750 ; Amyloidosis ; Anemia ; Asymptomatic ; Biological markers ; Biomarkers ; Biomarkers, Tumor - blood ; Cancer Research ; Care and treatment ; Chains ; Critical Care Medicine ; Diagnosis ; Female ; Hematology ; Humans ; Hypercalcemia ; Immunoglobulin Light Chains - blood ; Intensive ; Internal Medicine ; Leukemia ; Light ; Male ; Medical prognosis ; Medical records ; Medicine ; Medicine & Public Health ; Middle Aged ; Multiple myeloma ; Multiple Myeloma - blood ; Multiple Myeloma - diagnosis ; Oncology ; original-article ; Patients ; Physiological aspects ; Plasma ; Proteins ; Risk ; ROC Curve ; Sensitivity and Specificity ; Smoldering ; Subgroups ; Working groups</subject><ispartof>Leukemia, 2013-04, Vol.27 (4), p.941-946</ispartof><rights>Macmillan Publishers Limited 2013</rights><rights>COPYRIGHT 2013 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Apr 2013</rights><rights>Macmillan Publishers Limited 2013.</rights><rights>2012 Macmillan Publishers Limited All rights reserved 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c675t-34a2e38aa778234d5b435b8fb8b0004f141332b94cbd1ea64e8892c01a50ce583</citedby><cites>FETCH-LOGICAL-c675t-34a2e38aa778234d5b435b8fb8b0004f141332b94cbd1ea64e8892c01a50ce583</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/leu.2012.296$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/leu.2012.296$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23183428$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Larsen, J T</creatorcontrib><creatorcontrib>Kumar, S K</creatorcontrib><creatorcontrib>Dispenzieri, A</creatorcontrib><creatorcontrib>Kyle, R A</creatorcontrib><creatorcontrib>Katzmann, J A</creatorcontrib><creatorcontrib>Rajkumar, S V</creatorcontrib><title>Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>A markedly elevated serum free light chain (FLC) ratio may serve as a biomarker for malignant transformation in high-risk smoldering multiple myeloma (SMM) and identify patients who are at imminent risk of progression. We retrospectively studied the predictive value of the serum (FLC) assay in 586 patients with SMM diagnosed between 1970 to 2010. A serum involved/uninvolved FLC ratio ⩾100 was used to define high-risk SMM, which included 15% (
n
=90) of the total cohort. Receiver operating characteristics analysis determined the optimal FLC ratio cut-point to predict progression to symptomatic multiple myeloma (MM) within 2 years of diagnosis, which resulted in a specificity of 97% and sensitivity of 16%. Fifty-six percent of patients developed progressive disease during median follow-up of 52 months, but this increased to 98% in the subgroup of patients with FLC ratio ⩾100. The median time to progression in the FLC ratio ⩾100 group was 15 months versus 55 months in the FLC <100 group (
P
<0.0001). The risk of progression to MM within the first 2 years in patients with an FLC ratio ⩾100 was 72%; the risk of progression to MM or light chain amyloidosis in 2 years was 79%. We conclude that a high FLC ratio ⩾100 is a predictor of imminent progression in SMM, and such patients may be considered candidates for early treatment intervention.</description><subject>692/699/67/1857</subject><subject>692/699/67/1990/804</subject><subject>692/700/1750</subject><subject>Amyloidosis</subject><subject>Anemia</subject><subject>Asymptomatic</subject><subject>Biological markers</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - blood</subject><subject>Cancer Research</subject><subject>Care and treatment</subject><subject>Chains</subject><subject>Critical Care Medicine</subject><subject>Diagnosis</subject><subject>Female</subject><subject>Hematology</subject><subject>Humans</subject><subject>Hypercalcemia</subject><subject>Immunoglobulin Light Chains - blood</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Leukemia</subject><subject>Light</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical records</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - blood</subject><subject>Multiple Myeloma - diagnosis</subject><subject>Oncology</subject><subject>original-article</subject><subject>Patients</subject><subject>Physiological aspects</subject><subject>Plasma</subject><subject>Proteins</subject><subject>Risk</subject><subject>ROC Curve</subject><subject>Sensitivity and Specificity</subject><subject>Smoldering</subject><subject>Subgroups</subject><subject>Working groups</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqN0t1r1TAYBvAgijtO77yWgDC8sMd8tumNMIZfMPBCdx3S9O1ptrQ5Jq2w_36pZ85zxpDRi0Lzy5MmeRB6TcmaEq4-eJjXjFC2ZnX5BK2oqMpCSkmfohVRqirKmokj9CKlS0KWwfI5OmKcKi6YWqGLHxDnAXcRAHu36Sdse-NGHM3kAjYJG9y4MJh4BRF3IeI-oyK6dIXTEHwL0Y0bPMx-clsPeLgGn_VL9KwzPsGr2_cxuvj86efZ1-L8-5dvZ6fnhS0rORVcGAZcGVNVinHRykZw2aiuUQ0hRHRUUM5ZUwvbtBRMKUCpmllCjSQWpOLH6OMudzs3A7QWxikar7fR5T--1sE4fTgyul5vwm_NS1bXkuaAd7cBMfyaIU16cMmC92aEMCdNuVBCVWXFHkFZZlL9oW_v0cswxzGfhGalkBWVgvD_qZwlKc1Z4p_aGA_ajV3IG7HL0vqUMyU5o7LKav2Ayk8Lg7NhhM7l7wcTTvYm9GD81Kfg53zrYzqE73fQxpBShO7udCnRSwF1LqBeCqhzATN_s38jd_hv4zIodiBtl-pA3Nv1Q4E36FDhoQ</recordid><startdate>20130401</startdate><enddate>20130401</enddate><creator>Larsen, J T</creator><creator>Kumar, S K</creator><creator>Dispenzieri, A</creator><creator>Kyle, R A</creator><creator>Katzmann, J A</creator><creator>Rajkumar, S V</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20130401</creationdate><title>Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma</title><author>Larsen, J T ; Kumar, S K ; Dispenzieri, A ; Kyle, R A ; Katzmann, J A ; Rajkumar, S V</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c675t-34a2e38aa778234d5b435b8fb8b0004f141332b94cbd1ea64e8892c01a50ce583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>692/699/67/1857</topic><topic>692/699/67/1990/804</topic><topic>692/700/1750</topic><topic>Amyloidosis</topic><topic>Anemia</topic><topic>Asymptomatic</topic><topic>Biological markers</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - blood</topic><topic>Cancer Research</topic><topic>Care and treatment</topic><topic>Chains</topic><topic>Critical Care Medicine</topic><topic>Diagnosis</topic><topic>Female</topic><topic>Hematology</topic><topic>Humans</topic><topic>Hypercalcemia</topic><topic>Immunoglobulin Light Chains - blood</topic><topic>Intensive</topic><topic>Internal Medicine</topic><topic>Leukemia</topic><topic>Light</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medical records</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Multiple myeloma</topic><topic>Multiple Myeloma - blood</topic><topic>Multiple Myeloma - diagnosis</topic><topic>Oncology</topic><topic>original-article</topic><topic>Patients</topic><topic>Physiological aspects</topic><topic>Plasma</topic><topic>Proteins</topic><topic>Risk</topic><topic>ROC Curve</topic><topic>Sensitivity and Specificity</topic><topic>Smoldering</topic><topic>Subgroups</topic><topic>Working groups</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Larsen, J T</creatorcontrib><creatorcontrib>Kumar, S K</creatorcontrib><creatorcontrib>Dispenzieri, A</creatorcontrib><creatorcontrib>Kyle, R A</creatorcontrib><creatorcontrib>Katzmann, J A</creatorcontrib><creatorcontrib>Rajkumar, S V</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Larsen, J T</au><au>Kumar, S K</au><au>Dispenzieri, A</au><au>Kyle, R A</au><au>Katzmann, J A</au><au>Rajkumar, S V</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2013-04-01</date><risdate>2013</risdate><volume>27</volume><issue>4</issue><spage>941</spage><epage>946</epage><pages>941-946</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>A markedly elevated serum free light chain (FLC) ratio may serve as a biomarker for malignant transformation in high-risk smoldering multiple myeloma (SMM) and identify patients who are at imminent risk of progression. We retrospectively studied the predictive value of the serum (FLC) assay in 586 patients with SMM diagnosed between 1970 to 2010. A serum involved/uninvolved FLC ratio ⩾100 was used to define high-risk SMM, which included 15% (
n
=90) of the total cohort. Receiver operating characteristics analysis determined the optimal FLC ratio cut-point to predict progression to symptomatic multiple myeloma (MM) within 2 years of diagnosis, which resulted in a specificity of 97% and sensitivity of 16%. Fifty-six percent of patients developed progressive disease during median follow-up of 52 months, but this increased to 98% in the subgroup of patients with FLC ratio ⩾100. The median time to progression in the FLC ratio ⩾100 group was 15 months versus 55 months in the FLC <100 group (
P
<0.0001). The risk of progression to MM within the first 2 years in patients with an FLC ratio ⩾100 was 72%; the risk of progression to MM or light chain amyloidosis in 2 years was 79%. We conclude that a high FLC ratio ⩾100 is a predictor of imminent progression in SMM, and such patients may be considered candidates for early treatment intervention.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23183428</pmid><doi>10.1038/leu.2012.296</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 692/699/67/1857 692/699/67/1990/804 692/700/1750 Amyloidosis Anemia Asymptomatic Biological markers Biomarkers Biomarkers, Tumor - blood Cancer Research Care and treatment Chains Critical Care Medicine Diagnosis Female Hematology Humans Hypercalcemia Immunoglobulin Light Chains - blood Intensive Internal Medicine Leukemia Light Male Medical prognosis Medical records Medicine Medicine & Public Health Middle Aged Multiple myeloma Multiple Myeloma - blood Multiple Myeloma - diagnosis Oncology original-article Patients Physiological aspects Plasma Proteins Risk ROC Curve Sensitivity and Specificity Smoldering Subgroups Working groups |
title | Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma |
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