IMWGGUIDELINESFORSERUMFREELIGHTCHAINANALYSIS
INMULTIPLEMYELOMAANDRELATEDDISORDERS1

Forthemorethan3%ofmyelomapatientswhohavenonsecretoryor
oligosecretorydisease,andforthemajorityofpatientswithALamyloidosis(AL),
thetraditionalmethodsofmeasuringcirculatingmonoclonalimmunoglobulins
(electrophoresis,immunoelectrophoresis,immunofixationelectrophoresis,and
nephelometricmeasurementofimmunoglobulinheavychainsofserum)arenot
adequate.Thedevelopmentofanassaythatmeasuresserumimmunoglobulinfree
lightchainshasdemonstratedutilityformonitoringthesepatientsandforother
specificindications,suchasmonitoringheavilypretreatedpatientsatrelapse.
ThefollowingguidelinesfromtheInternationalMyelomaWorkingGroupdescribe
thepotentialusesoftheserumfreelightchain(SFLC)assayanddistinguishwhich
useshaveprovedtheirutilityandwhicharestillundergoinginvestigation.
SFLCassayforscreeningatdiagnosis
Thecombinationofserumimmunoelectrophoresis(IFE),serumprotein
electrophoresis(PEL),andserumfreelightchain(SFLC)assayare
recommendedforscreeningatdiagnosis.
Forthepurposeofscreeningformonoclonalproteinsforalldiagnosesexcept
AL,theSFLCassaycanreplacethe24hoururineIFE,BUTafterdiagnosis,
the24hoururineforPELandIFEshouldbedone.ForALscreening,the
urineIFEshouldstillbedoneinadditiontotheserumtests,includingSFLC.
PrognosticvalueoftheSFLCassay
BaselinevaluesoftheserumSFLCratioareprognosticfor:
o
MGUS(monoclonalgammopathyofundeterminedsignificance)
o
Smolderingmyeloma
o
Symptomaticmyeloma
o
Solitaryplasmacytoma
o
ALamyloidosis
TheFLCassayinresponseassessment
Treatmentrelatedimmunosuppressionoftheuninvolvedlightchain
(lambdaforkappapatients,andviceversa)canmaketheassayunreliablefor
monitoringresponseinpatientswithsecretorydisease.

1ADispenzierietal.InternationalMyelomaWorkingGroupguidelinesforserumfreelightchainanalysisinmultiplemyeloma
andrelateddisorders.Leukemia(2008),110.

---

RoutineserialuseoftheSFLCassayisrecommendedforoligosecretory
disease;hematologicresponsecanthereforebebestassessedwithSFLC
assayin:
o
ALamyloidosis
o
"Nonsecretory"myeloma(notyetfullyvalidated)
o
Lightchaindepositiondisease(notyetfullyvalidated)
ResponseCriteriaforFLC

Minimumdeemed
PR
CR
sCR
Progression
measurable
ALwithout
iFLC>/=100mg/l
50%reductionof
NormalrFLCand
ND
50%increaseof
measurable
iFLC
CRbyIFEand
iFLCto>100
serumorurineM
bonemarrow
mg/l
protein
ALwith
ND
ND
ND
ND
ND
measurable
serumorurineM
protein
MMwithout
iFLC>/=100mg/l
50%reductionof
ND
NormalrFLC&CR
50%increaseof
measurable
andrFLC
dFLC
byIFEandbone
dFLC
serumorurineM
abnormal
marrow
protein
MMwith
UseofFLCnot
UseofFLCnot
UseofFLCnot
NormalrFLC&CR
UseofFLCnot
measurable
recommended
recommended
recommended
byIFEandbone
recommended
disease
marrow
Abbreviations:iFLC,invrestricteddisease;dFLC,differencebetweeniFLCanduninvolvedFLC;rFLC,freelightchainratio;
ND,notdefined.
aMeasurableMproteinincludesserumMproteinofatleast1gper100mloraurineMproteinofatleast200mg/24hfor
myelomapatients(100mg/24hforALpatients).

TheFLCassayinthecontextofrenalinsufficiency
Althoughrenalfailureincreasesthelevelsofbothkappaandlambdalight
chains,itdoesnotresultinanabnormalratio.
InterpretingserialmeasurementsofiFLCinpatientswitholigosecretory
myeloma.LCDD,oramyloidosiswhoareondialysisorwhohavemarkedly
abnormalrenalfunctionisverychallenging,andresponseassessmenthas
notbeenvalidated.However,followingthedFLCoriFLCwhilenotingthe
uninvolvedlightchainscanprovideinformation.
Caveatswiththefreelightchain(FLC)assay
Clinical
o
Thetestmustbeinterpretedinthecontextofaclinicalsituation.Ifa
patientisinthemidstofaninfectionoraflareupofarheumatologic
condition,thetestshouldberepeatedatalaterdate.
Technical

---

o
TherecanbelottolotvariationbetweenbatchesofpolyclonalFLC
antisera,whichcanproduceinconsistentresults.
o
Somemonoclonallightchains(particularlykappa)donotdiluteina
linearfashionandmaybeunderestimated.
o
Changesintheaminoacidsequenceofthelightchainmayrender
certainlightchainepitopesunrecognizabletotheFLCreagents.
o
Extremepolymerizationcancauseanoverestimationoflightchains
byasmuchas10fold.
o
Veryhighlevelsoflightchainscancauseantigenexcess,whichinturn
canresultinfalselylowSFLCresultswithnephelometrictechniques.
o
Forlargemulticenterclinicaltrials,usingacentralizedlabisan
optiontoavoidlottolotvariationissues.

©2011InternationalMyelomaFoundation

---