NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines?)Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomarsionDecemberNCCNGuidelinesforPatients?availableat/patientsVersion2.2022,12/07/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:22:18AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion2.2022Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadex*ShajiK.Kumar,MD/Chair?ξMayoClinicCancerCenter*NatalieS.Callander,MD/ViceChair?ξUniversityofWisconsineCancerCenterKehindeAdekola,MD,MSCI??RobertH.LurieComprehensiveCancerCenterofNorthwesternUniversityLarryAnderson,Jr.,MD,PhD??UTSouthwesternSimmonsComprehensiveCancerCenterMuhamedBaljevic,MD??TξFred&PamelaBuffettCancerCenterEricaCampagnaro,MD?UniversityofMichiganRogelCancerCenterJorgeJ.Castillo,MD?Dana-Farber/BrighamandWomen’sCancerCenter|MassachusettsGeneralHospitalCancerCenterCaitlinCostello,MD??ξUCSanDiegoMooresCancerCenterSrinivasDevarakonda,MD??TheOhioStateUniversityComprehensiveCancerCenter-JamesCancerHospitalandSoloveResearchInstituteNouraElsedawy,MD?St.JudeChildren'sResearchHospital/TheUniversityofTennesseeeCenteratthewFaimanMDMBArehensiveCancerCenteriversityHospitalsSeidmanCancerCenternstituteAlfredGarfall,MD?AbramsonCancerCenterheUniversityofPennsylvaniaKellyGodby,MD?O'NealComprehensiveCancerCenteratUABJensHillengass,MD,PhD?RoswellParkComprehensiveCancerCenterLeonaHolmberg,MD,PhDξ?FredHutchinsonCancerResearchCenter/SeattleCancerCareAllianceMyoHtut,MD?TCityofHopeNationalMedicalCenterCarolAnnHuff,MD??TheSidneyKimmelComprehensiveCancerCenteratJohnsHopkinsMalinHultcrantz,MD,PhD??MemorialSloanKetteringCancerCenterYubinKang,MD??ξDukeCancerInstituteSarahLarson,MD?UCLAJonssonComprehensiveCancerCenterMichaelaLiedtke,MD?StanfordCancerInstituteThomasMartin,MD?UCSFHelenDillerFamilyComprehensiveCancerCenterJamesOmelMD￥eDouglasSborov,MD,MSc??TξHuntsmanCancerInstituteattheUniversityofUtahKennethShain,MD,PhD?MoffittCancerCenterKeithStockerl-Goldstein,MD?ξSitemanCancerCenteratBarnes-JewishHospitalandWashingtonUniversitySchoolofMedicineDonnaWeber,MD??TTheUniversityofTexasdiMScesPanelDisclosuresξBonemarrowtransplantation￥Patientadvocacy?Hematology*DiscussionsectionwritingTInternalmedicinecommittee?MedicaloncologyVersion2.2022,12/07/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:22:18AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion2.2022Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadexlievesthatthebestmanagementlievesthatthebestmanagementforanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.FindanNCCNMemberInstitution:/home/member-institutions.ofEvidenceandsusAllrecommendationsotherwisedNCategoriesofEvidenceandConsensus.NCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.ofGuidelinesUpdatesrTreatmentWMLPLRelapseWMLPLWHOCriteriaforLymphoplasmacyticLymphomaandWaldenstr?mMacroglobulinemiaWaldenstr?mMacroglobulinemiaInternationalWorkshopCriteria(WM/LPL-A)Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomaTherapy(WM/LPL-B)ResponseCriteriaforWM/LPL(WM/LPL-C)TheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatmentAnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualstancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetworkNCCNmakesnorepresentationsorwarrantiesofanykindregardingtheircontentuseorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinanywayTheNCCNbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.?2021.Version2.2022,12/07/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESVersion2.2022,12/07/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:22:18AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion2.2022Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadexUpdatesinVersion2.2022oftheNCCNGuidelinesforWM/LPLfromVersion1.2022include:WM/LPL-B3of4?TherapyforPreviouslyTreatedWM/LPLpThefollowingwasaddedtoOtherRecommendedRegimens:?Venetoclax(category2A)WM/LPL-B4of4?Referenceadded:CastilloJJ,AllanJN,SiddiqiT,AdvaniRH,MeidK,LeventoffC,etal.VenetoclaxinPreviouslyTreatedWaldenstr?mMacroglobulinemia.JClinOncol.2021Nov18:JCO2101194. oftheNCCNGuidelinesforWMLPLfromVersionincludeWMLPL-2?PrimaryTreatmentpAddedorIftransformation,seeNCCNGuidelinesforB-CellLymphomas,FollicularLymphoma?Footnoteorevised:CBC,completemetabolicpanel,andIgMevery3monthsfor2years,thenevery4–6monthsforadditional3years,thenevery6–12months.ProgressionbasedonIgMlevelsalone,withoutsymptoms,shouldnotbereasontoretreat.WM/LPL-B1of4?Anewpagewasadded:GeneralConsiderationsforSystemicTherapyforWM/LPL.WM/LPL-B2of4?PrimaryTherapypPreferredRegimens:Zanubrutinibwasaddedasacategory1recommendation.pOtherRecommendedRegimens:Cyclophosphamide/doxorubicin/vincristine/prednisone/rituximabwasremoved.?Footnotesweremovedtoanewpage:GeneralConsiderationsforSystemicTherapyforWM/LPL.?Footnoteaadded:SeeGeneralConsiderationsforSystemicTherapyforWM/LPL(WM/LPL-B1of4).(AlsoforWM/LPL-B3of4)WM/LPL-B3of4?TherapyforPreviouslyTreatedWM/LPLpPreferredRegimens:Zanubrutinibwasaddedasacategory1recommendation.?Footnotesweremovedtoanewpage:GeneralConsiderationsforSystemicTherapyforWM/LPL.?Footnotedwasrevised:Ofatumumabmaybeusedforrituximab-intolerantindividualsasasingleagentorincombinationtherapyanywherethatrituximabisgiven.Whileofatumumabisnolongercommerciallyavailable,itmaybeobtainedforclinicaluse.WM/LPL-B4of4?Referenceadded:TamCS,OpatS,D'SaS,etal.Arandomizedphase3trialofzanubrutinibvsibrutinibinsymptomaticWaldenstr?mmacroglobulinemia:theASPENstudy.Blood2020;136:2038-2050.iveofthetumor(RebiopsyifconsultmaterialisquatetissueingtoestablishdiagnosisHistoryandphysicalexamdifferentialplateletcountiontestsLFTsasclinicallyindicatedPeripheralbloodsmearSerumBUNcreatinineelectrolytes,albumin,calcium,serumuricacid,serumLDH,dbetamicroglobulinCreatinineclearancecalculatedormeasureddirectly)Serumquantitativeimmunoglobulinsserumproteinelectrophoresisiveofthetumor(RebiopsyifconsultmaterialisquatetissueingtoestablishdiagnosisHistoryandphysicalexamdifferentialplateletcountiontestsLFTsasclinicallyindicatedPeripheralbloodsmearSerumBUNcreatinineelectrolytes,albumin,calcium,serumuricacid,serumLDH,dbetamicroglobulinCreatinineclearancecalculatedormeasureddirectly)Serumquantitativeimmunoglobulinsserumproteinelectrophoresis(SPEP),serumationelectrophoresisSIFEralbonemarrowaspirateandbiopsyincludingimmunohistochemistryIHCdormultiparameterflowcytometryChestabdominalpelvicCTwithcontrastwhenpossibleMYD,dL265PAS-PCRtestingofbonemarrowmviscositygenemutationtestingforpatientsbeingconsideredforibrutinibendHIVConsidercoagulationandorvonWillebranddiseasetestingifsymptomspresentexcessbruisingorbleedingorifclinicallyindicateddagglutinins?NeurologyconsulthAntiMAGantibodiesantiGMh?Nerveconductionstudy(NCS)/electromyogram(EMG)hFatpadsamplingand/orcongoredstainingofbonemarrowforamyloidhRetinalexamifIgM0g/dLorifhyperviscosityissuspected)4-hurinefortotalprotein,urineproteinelectrophoresis(UPEP),andurinetionelectrophoresisUIFEsuesubtypingwithmassspectrometryifindicatedBrainspineMRIifCNSsymptomsnemiaandtopeniasatedwithkyadenopathymptomsSymptomsirelatedto:?Hyperviscosityropathynomegaly?Amyloidosis?Coldagglutinin?CryoglobulinemiaimaryTreatment(WM/LPL-2)texcludecLymphoplasmacyticlymphomaLPLdoesencompassIgGIgAserumfreelightocritpositivethenrepeattestingofinitialserumIgMandobtainallsubsequentserumIgMlevelsunderwarmconditions.ngwithsuspecteddiseaserelatedtoperipheralneuropathychainaloneandnonsecretorysubtypesthoughmakesup<5%ofallLPLs.TheMacroglobulinemia(WM/LPL-A).ofcasesandspeNCCNGuidelinesVersion2.2022Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadexDIAGNOSISINDICATIONSFORDIAGNOSISINDICATIONSFORTREATMENTtaintainCircumstances?HematopathologywithatleastonereviewwithatleastoneCDCDsIgM+;CD5,CD10,inCD23indMYDwildtypeoccursin<10%ofpatientsandshouldnotbeusedtodMYDwildtypeoccursin<10%ofpatientsandshouldnotbeusedtoexcludediagnosisofWMifothercriteriaaremet.eStudieshaveshownthatmutationsineStudieshaveshownthatmutationsinthisgenearefoundinupto40%ofbSeeWHOCriteriaforLymphoplasmacyticLymphomaandWaldenstr?mfConsiderinpatientswithsuspectedcryoglobulinemia.patientswithWMfConsiderinpatientswithsuspectedcryoglobulinemia.treatmentofnon-IgMLPLsparallelsthatofIgM-secretingLPLs,buttheseareuleoutamyloidosisinpatientspresentingwithnephroticsyndromeorlesslikelyuleoutamyloidosisinpatientspresentingwithnephroticsyndromeorunexplainedcardiacproblems.iConfirmsymptomsarenotrelatedtoorcausedbycomorbidities.relatedunexplainedcardiacproblems.iConfirmsymptomsarenotrelatedtoorcausedbycomorbidities.myeloma.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.WM/LPL-1Version2.2022,12/07/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.derpreviouslyusedsifwelltoleratedanddresponselpternativetherapylpternativetherapylpformationseeNCCNGuidelinesforphomaPrintedbyMinTangonderpreviouslyusedsifwelltoleratedanddresponselpternativetherapylpternativetherapylpformationseeNCCNGuidelinesforphomaNCCNGuidelinesVersion2.2022Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadexPRIMARYTREATMENTjrrsymptomaticrialIftransformation,seeNCCNGuidelinesforB-CellLymphomas,FollicularLymphomaRELAPSERELAPSE?Completemresponsem?VerygoodpartialmresponsemialminorialminormdiseasemdiseasemObserven,ountilasemoountilivediseasemerrituximabforerapyomsIfpersistentomsjIntentoftherapyshouldbebasedonpalliationofsymptoms,notnecessarilylevelsofIgMunlessthepatientisexhibitingevidenceofsymptomatichyperviscosity.lSeeWaldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomaTherapy(WM/LPL-B).kPlasmapheresisshouldbeperformedforpatientswithsymptomatichyperviscosity,andbeforetreatmentwithrituximab-containingregimeninpatientswithIgM≥4000mg/dL.IgMshouldbemonitoredcloselyinthesepatientsthereafterandplasmapheresisshouldbeconsideredagainifsymptomatichyperviscosityrecursorifIgMis≥4000mg/dLwhileonrituximab-containingtherapy.RBCtransfusion,ifindicated,shouldbedoneafterplasmapheresistopreventaddedhyperviscosityload.mSeeResponseCriteriaforWM/LPL(WM/LPL-C).nSeeNCCNGuidelinesforSurvivorship.oCBC,completemetabolicpanel,andIgMevery3monthsfor2years,thenevery4–6monthsforadditional3years,thenevery6–12months.ProgressionbasedonIgMlevelsalone,withoutsymptoms,shouldnotbereasontoretreat.pCautionshouldbeusedwhenre-treatingwithmyelosuppressiveregimensduetocumulativetoxicities.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.WM/LPL-2Version2.2022,12/07/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.*Sumoftotalpointsintable1ohaveplasmacyticdifferentiationpermissionfromSwerdlowSHCampoEHarrisNLetal*Sumoftotalpointsintable1ohaveplasmacyticdifferentiationpermissionfromSwerdlowSHCampoEHarrisNLetalWorldHealthOrganizationClassificationofTumoursofHaematopoieticandLymphoiduesrevisedtheditionIARCLyonNCCNGuidelinesVersion2.2022Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadexWHOCRITERIAFORLYMPHOPLASMACYTICLYMPHOMAANDWALDENSTR?MMACROGLOBULINEMIA?Waldenstr?mmacroglobulinemia:pLymphoplasmacyticlymphomawithbonemarrowinvolvementandIgMmonoclonalgammopathyofanyconcentrationAdaptedwithpermission.OwenRG,TreonSP,Al-KatibA,etal.ClinicopathologicalDefinitionofWaldenstrom'sMacroglobulinemia:ConsensusPanelRecommendationsfromtheSecondInternationalWorkshoponWaldenstom'sMacroglobulinemia.SeminOncol.2003;30:110-115.WALDENSTR?MMACROGLOBULINEMIAINTERNATIONALWORKSHOPCRITERIAProposedCriteriafortheDiagnosisofWaldenstr?mMacroglobulinemia?IgMmonoclonalgammopathyofanyconcentration?Bonemarrowinfiltrationbysmalllymphocytes,plasmacytoidcells,andplasmacells?Diffuse,interstitial,ornodularpatternofbonemarrowinfiltration?CD19+,CD20+,sIgM+;CD5,CD10,CD23canbeexpressedinsomecasesofWaldenstr?mmacroglobulinemiaanddoesnotexcludediagnosis.ReprintedwithpermissionfromElsevierOwenRGDevelopingdiagnosticcriteriainWaldenstrmsmacroglobulinemiaSeminOncol2003;30:196-200.REVISEDIPSSWALDENSTR?MMACROGLOBULINEMIASCORINGSYSTEMriteriafortheDiagnosisofWaldenstrmMacroglobulinemiaonlyatthetimeofinitialtreatmentprognosticationTable1Age<650Age66–751Age>752B2microglobulin>4mg/L11Serumalbuming/dL1Table20VeryLow123helPDuhamelAetalArevisedinternationalprognosticscoresystemforWaldenstrmsmacroglobulinemiaLeukemia2019;33:2654-2661.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.WM/LPL-AVersion2.2022,12/07/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.?ScreenforHIVandhepatitisC,asclinicallyindicated.?SerialserumIgAandIgGlevelsshouldbecarefullymonitoredasthesecanbedepletedwithWMtherapies.Regimenscontainingbortezomibandvincristineareassociatedwithhigherriskoftreatment-relatedperipheralneuropathy,especiallyin?ScreenforHIVandhepatitisC,asclinicallyindicated.?SerialserumIgAandIgGlevelsshouldbecarefullymonitoredasthesecanbedepletedwithWMtherapies.Regimenscontainingbortezomibandvincristineareassociatedwithhigherriskoftreatment-relatedperipheralneuropathy,especiallyinthosewithdiseaserelatedbaselineneuropathyClosemonitoringoralternativetherapiesshouldbeconsideredinsomepatients?Bothweeklyandtwice-weeklydosingschemasofbortezomibmaybeappropriate;weeklypreferred.?Carfilzomibmaybeusedonceortwiceweeklyandatdifferentdoses.?AnFDA-approvedbiosimilarisanappropriatesubstituteforrituximab.beavoidedinpatientswhomaybepotentialautologousHCTorwhoaresymptomatictoavoidaggravationofserumviscosityonthebasisofrituximab-relatedIgMflare.Rituximaborofatumumab?Administerherpeszosterprophylaxisforallpatientstreatedwithproteasomeinhibitorsandnucleosideanalogs.isactivediseasePCRitisconsideredtreatmentmanagementandnotprophylactictherapyIncasesofHBcAbpositivitymonitoredwithserialhepatitisBviralload.Ifcandidatesforhematopoieticcelltransplantation(HCT)candidates.mayalsobeheldinpatientswithelevatedserumIgMlevelsforinitialtreatmentcycles.Bloodwarmersshouldbeusedforapheresisifcyclophosphamide/rituximab.beforetreatmentwithrituximaborofatumumabforasymptomaticWaldenstrmmacroglobulinemiapatientswithanIgM0mg/dLProphylacticantiviraltherapywithentecavirisrecommendedforanypatientwhoisHBsAg-positiveandreceivinganti-CD20therapy.tiviraltherapyispreferredhoweverifthereisaconcurrenthighlevelhepatitisBsurfaceantibodythesepatientsmaybeNCCNGuidelinesVersion2.2022Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadexGENERALCONSIDERATIONSFORSYSTEMICTHERAPYFORWM/LPLFrailtyassessmentFrailtyassessmentshouldbeconsideredinolderadultsSeeNCCNGuidelinesforOlderAdultOncology.pheresisshouldalsobeconsideredcryoprecipitateorcryoglobulinarepresent.TestforTestforhepatitisBbeforestartingcarfilzomib,rituximab,orofatumumab.PneumocystisjiroveciPneumocystisjirovecipneumoniaPJP)prophylaxisshouldbeconsideredforpatientsreceivingbendamustine/rituximaborfludarabine/CarfilzomibcanpotentiallycausecardiacCarfilzomibcanpotentiallycausecardiacandpulmonarytoxicity,especiallyinelderlypatients.?Subcutaneousbortezomibisthepreferredmethod?Subcutaneousbortezomibisthepreferredmethodofadministration.Substitutionsreceivedthefirstfulldoseofrituximabbyintravenousinfusion.?Rituximabandhyaluronidasehumaninjectionforsubcutaneousreceivedthefirstfulldoseofrituximabbyintravenousinfusion.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version2.2022,12/07/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.WM/LPL-BOF4PrintedbyMinTangon3/14/20227:22:18AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion2.2022Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadexPRIMARYTHERAPYFORWM/LPLa(Orderofregimensisalphabeticalanddoesnotindicatepreference)ens?Bendamustine/rituximab?Bortezomib/dexamethasone/rituximabbrutinibrituximabcategory?Rituximab/cyclophosphamide/dexamethasone?Zanubrutinib(category1)ecommendedRegimens?Bendamustine?Bortezomib±rituximabb?Bortezomib/dexamethasone?Carfilzomib/rituximab/dexamethasone?Cladribine±rituximabcudarabinerituximabcudarabinerituximabczomibrituximabdexamethasoneuximabuximabcyclophosphamideprednisoneaSeeGeneralConsiderationsforSystemicTherapyforWM/LPL(WM/LPL-B1of4).bConsiderforpatientspresentingwithsymptomatichyperviscosity,orinwhomrapidIgMreductionisrequired.cMaybeassociatedwithdiseasetransformationand/ordevelopmentofMDS/AMLinpatientswithWaldenstr?mmacroglobulinemia.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version2.2022,12/07/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.WM/LPL-B2OF4WM/LPL-B3OF4PrintedbyMinTangon3/14/20227:22:18AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllWM/LPL-B3OF4NCCNGuidelinesVersion2.2022Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadexTHERAPYFORPREVIOUSLYTREATEDWM/LPLa(Orderofregimensisalphabeticalanddoesnotindicatepreference)ensamustinerituximab?Bortezomibamustinerituximab?Ibrutinib±rituximab(category1)?Rituximab/cyclophosphamide/dexamethasone?Zanubrutinib(category1)adribineadribinerituximabcbrutinib?Bortezomib±?Bortezomib±rituximabb?Bortezomib/dexamethasonedarabinecyclophosphamiderituximabcudarabinerituximabcyclophosphamideudarabinerituximabcuximab?Rituximab/cyclophosphamide/prednisone?VenetoclaxinCircumstancesolimusOfatumumabforrituximabintolerantolimusHematopoieticCellTransplantaSeeGeneralConsiderationsforSystemicTherapyforWM/LPL(WM/LPL-B1of4).bConsiderforpatientspresentingwithsymptomatichyperviscosity,orinwhomrapidIgMreductionisrequired.cMaybeassociatedwithdiseasetransformationand/ordevelopmentofMDS/AMLinpatientswithWaldenstr?mmacroglobulinemia.dOfatumumabmaybeusedforrituximab-intolerantindividualsasasingleagentorincombinationtherapyanywherethatrituximabisgiven.Whileofatumumabisnolongercommerciallyavailable,itmaybeobtainedforclinicaluse.eShouldideallybeundertakeninthecontextofaclinicaltrial.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version2.2022,12/07/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:22:18AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion2.2022Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadexSUGGESTEDREFERENCESCastilloJJ,AllanJN,SiddiqiT,AdvaniRH,MeidK,LeventoffC,etal.VenetoclaxinPreviouslyTreatedWaldenstr?mMacroglobulinemia.JClinOncol.2021Nov18:JCO2101194.ChesonBDRummelMJBendamustinerebirthofanolddrug.JClinOncol2009;27:1492-1501.osAKyrtsonisMCetalPrimarytreatmentenstromsmacroglobulinemiawithdexamethasonerituximabandcyclophosphamide.JClinOncol2007;25:3344-3349.poulosAZervasCetalPredictivefactorsfortuximabinWaldenstromsmacroglobulinemiaClinLymphoma2005;5:270-272.mopoulosMAGertzMAKastritisEetalUpdateontreatmentomtheFourthInternationalWorkshoponWaldenstromsMacroglobulinemia.JClinOncol2009;27:120-126.eatmentofWaldenstromsmacroglobulinemiawithrituximab.JClinOncol2002;20:2327-2333.astritisEOwenRetalTreatmentrecommendationsforpatientswithWaldenstromsmacroglobulinemiaWMandrelateddisorders:consensusfromtheSeventhInternationalWorkshoponWM.Blood2014;124:1404-1411.DimopoulosMA,TedeschiA,TrotmanJ,etal.Phase3trialofibrutinibplusrituximabinWaldenstr?m'smacroglobulinemia.NEnglJMed2018;378:2399-2410.GertzMARu