華氏巨球蛋白血癥淋巴漿細(xì)胞淋巴瘤2023.v1-NCCN（英文版）

NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines?)Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomarsionJulyNCCNGuidelinesforPatients?availableat/patientsVersion1.2023,07/06/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon7/14/20229:44:12AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion1.2023Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadex*ShajiK.Kumar,MD/Chair?ξMayoClinicCancerCenter*NatalieS.Callander,MD/ViceChair?ξUniversityofWisconsineCancerCenterKehindeAdekola,MD,MSCI??RobertH.LurieComprehensiveCancerCenterofNorthwesternUniversityLarryD.Anderson,Jr.,MD,PhD??UTSouthwesternSimmonsComprehensiveCancerCenterMuhamedBaljevic,MD??TξVanderbilt-IngramCancerCenterEricaCampagnaro,MD?UniversityofMichiganRogelCancerCenter*JorgeJ.Castillo,MD?Dana-Farber/BrighamandWomen’sCancerCenter|MassachusettsGeneralHospitalCancerCenterCaitlinCostello,MD??ξUCSanDiegoMooresCancerCenterChristopherD'Angelo,MD??Fred&PamelaBuffettCancerCenterSrinivasDevarakonda,MD??TheOhioStateUniversityComprehensiveCancerCenter-JamesCancerHospitalandSoloveResearchInstituteNouraElsedawy,MD?St.JudeChildren'sleCenterAlfredGarfall,MD?AbramsonCancerCenterheUniversityofPennsylvaniaKellyGodby,MD?O'NealComprehensiveCancerCenteratUABJensHillengass,MD,PhD?RoswellParkComprehensiveCancerCenterLeonaHolmberg,MD,PhDξ?FredHutchinsonCancerResearchCenter/SeattleCancerCareAllianceMyoHtut,MD?TCityofHopeNationalMedicalCenterCarolAnnHuff,MD??TheSidneyKimmelComprehensiveCancerCenteratJohnsHopkinsMalinHultcrantz,MD,PhD??MemorialSloanKetteringCancerCenterYubinKang,MD??ξDukeCancerInstituteSarahLarson,MD?UCLAJonssonComprehensiveCancerCenterHansLee,MD??TheUniversityofTexasMichaelaLiedtke,MD?StanfordCancerInstituteThomasMartin,MD?UCSFHelenDillerFamilyComprehensiveCancerCenterJamesOmelMD￥eAaronRosenberg,MD??ξmprehensiveCancerCenterDouglasSborov,MD,MSc??TξHuntsmanCancerInstituteattheUniversityofUtahKeithStockerl-Goldstein,MD?ξSitemanCancerCenteratBarnes-JewishHospitalandWashingtonUniversitySchoolofMedicineJasonValent,MD??CaseComprehensiveCancerCenter/UniversityHospitalsSeidmanCancerCenterandClevelandClinicTaussignstitutediMScesPanelDisclosuresξBonemarrowtransplantation￥Patientadvocacy?Hematology*DiscussionsectionwritingTInternalmedicinecommittee?MedicaloncologyVersion1.2023,07/06/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon7/14/20229:44:12AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion1.2023Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadexlievesthatthebestmanagementlievesthatthebestmanagementforanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.FindanNCCNMemberInstitution:/home/member-institutions.ofEvidenceandsusAllrecommendationsotherwisedNCategoriesofEvidenceandConsensus.NCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.ofGuidelinesUpdatespWMLPLAsymptomaticorMinimallySymptomatic(WM/LPL-2)RelapseWMLPLWHOCriteriaforLymphoplasmacyticLymphomaandWaldenstr?mMacroglobulinemiaWaldenstr?mMacroglobulinemiaInternationalWorkshopCriteria(WM/LPL-A)Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomaTherapy(WM/LPL-B)ResponseCriteriaforWM/LPL(WM/LPL-C)ManagementofBingNeelSyndrome(BNS-1)Abbreviations(ABBR-1)TheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatmentAnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualstancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetworkNCCNmakesnorepresentationsorwarrantiesofanykindregardingtheircontentuseorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinanywayTheNCCNbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.?2022.Version1.2023,07/06/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESVersion1.2023,07/06/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon7/14/20229:44:12AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion1.2023Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadexoftheNCCNGuidelinesforWMLPLfromVersionincludeWMLPL-1?Workup:pEssential:?Thirdbulletremoved:Liverfunctiontests(LFTs)asclinicallyindicated?4thbulletmodified:ComprehensiveMetabolicPanel(CMP)includingserumbloodureanitrogen(BUN)/creatinine,electrolytes,albumin,calcium,andliverfunctiontests(LFTs)?9thbulletmodified:Chest/abdominal/pelvicCTwithcontrastand/orPET-CTwhenpossiblepUsefulinCertainCircumstances:?2ndbulletmodified:CXCR4genemutationtestingforpatientsbeingconsideredforibrutinibBruton’styrosinekinase(BTK)inhibitors?Bulletremoved:Brain/spineMRI,ifCNSsymptoms?14thbulletadded:Ifcentralnervoussystem(CNS)symptoms,seeBNS-1?Headerremoved:IndicationsforTreatment?Added:AsymptomaticorminimallysymptomaticWMLPL-2otheguidelinesAsymptomaticorMinimallySymptomaticWMLPL-3?Thispagehasbeenextensivelyrevised.WM/LPL-B2of4?PrimaryTherapyforWM/LPLpPreferredRegimens:?ThefollowingregimenhasbeenmovedtoOtherRecommendedRegimens:RituximabcyclophosphamidedexamethasonepOtherRecommendedRegimens:?Thefollowingregimenshavebeenremoved:–Bortezomib±rituximabBortezomibdexamethasone–Cladribine±rituximab–Fludarabine±rituximabFludarabinecyclophosphamiderituximabCONTINUEDPrintedbyMinTangon7/14/20229:44:12AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion1.2023Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadexoftheNCCNGuidelinesforWMLPLfromVersionincludeWM/LPL-B3of4?TherapyforPreviousTreatedWM/LPLpOtherRecommendedRegimens:?ThefolowingregimenshavebeenmovedtoUsefulinCertainCircumstances:–Cladribine±rituximab–Fludarabine±rituximab–Fludarabine/cyclophosphamide/rituximab?ThefollowingregimenhasbeenaddedtoOtherRecommendedRegimens:Ixazomibrituximab/dexamethasone?Thefollowingregimenshavebeenremoved:–Bortezomib±rituximabBortezomibdexamethasoneWM/LPL-B4of4?Referenceshavebeenupdated.hasbeenaddedtotheguidelinesManagementofBingNeelSyndromeABBR1theguidelinesAbbreviationswithatleastoneiveofthetumor(RebiopsyifconsultmaterialisquatetissueingtoestablishdiagnosisCompletebloodcountCBCdifferentialplateletcountPeripheralbloodsmearComprehensiveMetabolicPanel(CMP)includingserumbloodureanitrogen(BUN)/tinineelectrolytesalbumincalciumandliverfunctiontestsLFTsSerumuricacidserumlactatedehydrogenase(LDH),andbeta-2microglobulinCreatinineclearancecalculatedormeasuredwithatleastoneiveofthetumor(RebiopsyifconsultmaterialisquatetissueingtoestablishdiagnosisCompletebloodcountCBCdifferentialplateletcountPeripheralbloodsmearComprehensiveMetabolicPanel(CMP)includingserumbloodureanitrogen(BUN)/tinineelectrolytesalbumincalciumandliverfunctiontestsLFTsSerumuricacidserumlactatedehydrogenase(LDH),andbeta-2microglobulinCreatinineclearancecalculatedormeasureddirectly)Serumquantitativeimmunoglobulinsserumproteinelectrophoresis(SPEP),serumationelectrophoresisSIFEralbonemarrowaspirateandbiopsyincludingimmunohistochemistryIHCdormultiparameterflowcytometrystabdominalpelvicCTwithcontrastandorPETCTwhenpossible?MYD88L265PdAlleleSpecific-polymerasechainreaction(AS-PCR)testingofbonendHIVConsidercoagulationandorvonWillebranddiseasetestingifsymptomspresentexcessbruisingorbleedingorifclinicallyindicateddagglutinins?NeurologyconsulthAntimyelinassociatedglycoproteinMAG)antibodies/anti-GM1h?Nerveconductionstudy(NCS)/electromyogram(EMG)hFatpadsamplingand/orcongoredstainingofbonemarrowforamyloidhRetinalexaminationifIgM0g/dLorifhyperviscosityissuspected)4-hurinefortotalprotein,urineproteinelectrophoresis(UPEP),andurinetionelectrophoresisUIFEsuesubtypingwithmassspectrometryifindicatedIfcentralnervoussystemCNS)symptoms,SeeBNS-1omaticnemiaandtopeniasatedwithkyadenopathymptomscLymphoplasmacyticlymphomaLPLencompassesIgGIgAserumfreelightchainLPLandcanimpactibrutinibresponse.gIfcryocritispositive,thenrepeattestingofinitialserumIgM,andobtainallsubsequentdtoperipheralneuropathyruleoutiConfirmsymptomsarenotrelatedtoorcausedbycomorbidities.Asymptomaticorminimallynitoring?HematopathologyreviewofallslidestexcludeglobulinemiaMacroglobulinemia(WM/LPL-A).fConsiderinpatientswithsuspectedcryoglobulinemia.eStudieshaveshownthatmutationsinthisgenearefoundinupto40%ofpatientswithWM/aloneandnonsecretorysubtypes,althoughmakesup<5%ofallLPLs.ThetreatmentofserumIgMlevelsunderwarmconditions.amyloidosisinpatientspresentingwithnephroticsyndromeorunexplainedcardiacproblems.ofcasesandsNCCNGuidelinesVersion1.2023Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadexDIAGNOSISINDICATIONSFORWORKUPDIAGNOSISINDICATIONSFOREssentialistoryandphysicalexaminationmviscositySymptomsirelatedmviscositySymptomsirelatedto:?Hyperviscosityropathynomegaly?Amyloidosis?ColdagglutininSeePrimaryTreatmentWM/LPL-3immunophenotypeCD19+,CD20+,sIgM+;CD5,CD10,inCD23inaFrailtyassessmentshouldbeconsideredinolderadults.SeeNCCNGuidelinesforOlderCriteriaCriteriaforLymphoplasmacyticLymphomaandWaldenstrmnon-IgMLPLsparallelsthatofIgM-secretingLPLs,butthesearelesslikelytohaveeitherhyperviscosityassociatedwiththem,orautoimmune-relatedneuropathy.ItisimportanttodifferentiatefromIgMMGUSorIgMmultiplemyeloma.WMifothercriteriaaremet.dMYD88wild-typeoccursin<10%ofpatientsandshouldnotWMifothercriteriaaremet.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version1.2023,07/06/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.WM/LPL-1PrintedbyMinTangon7/14/20229:44:12AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion1.2023Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadexAsymptomaticjnyearsCalculateasymptomaticiskscoreusingkiskscoreusingk?Bonemarrow?Bonemarrowinvolvement(%)?SerumIgMlevel(mg/dL)?Serumbeta-2microglobulinlevel(mg/L)?Serumalbuminlevel(g/dL)nyearsHighRiskMediantimetoprogression:1.8yearsFOLLOW-UPMonitorevery12monthswithCBC,ComprehensiveMetabolicobulinsMonitorevery6monthswithCBC,CMP,SPEP,serumimmunoglobulinsMonitorevery3monthswithCBC,CMP,SPEP,serumimmunoglobulinsINDICATIONSFORTREATMENTSymptomslrelatedto:?Hyperviscositymopathyomegaly?Amyloidosis?Coldagglutinindiseasen?Cryoglobulinemian?Anemiaandothercytopenias?Bulkyadenopathy?Bsymptoms?cytopeniasSeePrimary TreatmentWMLPL-3jReservetherapyonlyforsymptomaticpatients,asuntreatedasymptomaticpatientshavesimilarsurvivalthanageandsex-matchedindividualsofthegeneralpopulation.kRiskscorecalculatoravailableat.Allvaluestakenatapproximatelythesametime.lConfirmsymptomsarenotrelatedtoorcausedbyothercomorbidities.mRetinalexaminationonceayearifserumIgMlevel>3000mg/dL.ConsidertherapyinasymptomaticpatientswithserumIgMlevel>6000mg/dL.nDetectionofcoldagglutininsorcryoglobulinsintheabsenceofsymptomsdoesnotrepresentacriteriontotreat.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.WM/LPL-2Version1.2023,07/06/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon7/14/20229:44:12AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion1.2023Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadexPRIMARYTREATMENToRELAPSEConsiderpreviouslyusedObserves,tuntilObserves,tuntildresponseqvixeddurationotherapyixeddurationotherapyrrsymptomatichBTKmensrialionternativetherapyquonorxicityCNdelinesorBCellFolliculartionseeCNdelinesorBCellFollicularIfpersistentsymptomsdiseaser(WM/LPL-B).qSeeWaldenstr?mMacroglobulinemia/(WM/LPL-B).sponseCriteriaforWMLPLWMLPLCssponseCriteriaforWMLPLWMLPLCsSeeNCCNGuidelinesforSurvivorship.levelsofIgMunlessthepatientisexhibitingevidenceofsymptomatichyperviscosity.tCBCcompletemetabolicpanel,andIgMevery3tCBCcompletemetabolicpanel,andIgMevery3monthsfor2years,theneverynthsProgressionnthsProgressionbasedonIgMlevelsalone,withoutsymptoms,shouldnotbereasontoretreat.uMaintenancerituximabmaybeconsideredinselectpatientsafterchemoimmunotherapyregimens.vCautionshouldbeusedwhenre-treatingwithmyelosuppressiveregimensduetocumulativetoxicities.withIgM≥4000mg/dL.IgMshouldbemonitoredcloselyinthesepatientsthereafterandplasmapheresisshouldbeconsideredagainifsymptomatichyperviscosityrecursorifIgMis≥4000mg/dLwhileonrituximab-containingtherapy.RBCtransfusion,ifindicated,shouldbedoneafterplasmapheresistopreventaddedhyperviscosityload.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.WM/LPL-3Version1.2023,07/06/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.*Sumoftotalpointsintable1ohaveplasmacyticdifferentiationpermission*Sumoftotalpointsintable1ohaveplasmacyticdifferentiationpermissionfromSwerdlowSHCampoEHarrisNLetalWorldHealthOrganizationClassificationofTumoursofHaematopoieticandLymphoiduesrevisedtheditionIARCLyonNCCNGuidelinesVersion1.2023Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadexWHOCRITERIAFORLYMPHOPLASMACYTICLYMPHOMAANDWALDENSTR?MMACROGLOBULINEMIA?Waldenstr?mmacroglobulinemia:pLymphoplasmacyticlymphomawithbonemarrowinvolvementandIgMmonoclonalgammopathyofanyconcentrationAdaptedwithpermission.OwenRG,TreonSP,Al-KatibA,etal.ClinicopathologicalDefinitionofWaldenstrom'sMacroglobulinemia:ConsensusPanelRecommendationsfromtheSecondInternationalWorkshoponWaldenstom'sMacroglobulinemia.SeminOncol2003;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/dL1Table20VeryLow123hrelPDuhamelAetalArevisedinternationalprognosticscoresystemforWaldenstrmsmacroglobulinemiaLeukemia2019;33:2654-2661.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.WM/LPL-AVersion1.2023,07/06/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.?SerialserumIgAandIgGlevelsshouldbecarefullymonitoredasthesecanbedepletedwithWMtherapies.Regimenscontainingbortezomibandvincristineareassociatedwithhigherriskoftreatment-relatedperipheralneuropathy,especiallyinthosewithdiseaserelatedbaselineneuropathy.Closemonitoringoralternative?SerialserumIgAandIgGlevelsshouldbecarefullymonitoredasthesecanbedepletedwithWMtherapies.Regimenscontainingbortezomibandvincristineareassociatedwithhigherriskoftreatment-relatedperipheralneuropathy,especiallyinthosewithdiseaserelatedbaselineneuropathy.Closemonitoringoralternativetherapiesshouldbeconsideredinsomepatients.?Bothweeklyandtwice-weeklydosingschemasofbortezomibmaybeappropriate;weeklyispreferred.?Carfilzomibmaybeusedonceortwiceweeklyandatdifferentdoses.?AnU.S.FoodandDrugAdministration(FDA)-approvedbiosimilarisanappropriatesubstituteforrituximab.beavoidedinpatientswhomaybepotentialautologousHCTdLorwhoaresymptomatictoavoidaggravationofserumviscositybasedonrituximab-relatedIgMflare.Rituximaborofatumumabcryoprecipitateorcryoglobulinarepresent.ingRecommendations?Administerherpeszosterprophylaxisforallpatientstreatedwithproteasomeinhibitorsandnucleosideanalogs.erapyIfthereisactivediseasePCRitisconsideredtreatmentmanagementandnotprophylactictherapyIncasesofhepatitisBthesepatientsmaybemonitoredwithserialhepatitisBviralload.cyclophosphamide/rituximab.?ProphylacticantiviraltherapywithentecavirisrecommendedforanypatientwhoishepatitisBsurfaceantigen-positiveandreceivinganti-mayalsobeheldinpatientswithelevatedserumIgMlevelsforinitialtreatmentcycles.BloodwarmersshouldbeusedforapheresisifitivityprophylacticantiviraltherapyispreferredhoweverifthereisaconcurrenthighlevelhepatitisBsurfaceantibodybeforetreatmentwithrituximaborofatumumabforasymptomaticWaldenstrmmacroglobulinemiapatientswithanIgMmg/Ifcandidatesforhematopoieticcelltransplantation(HCT)candidates.NCCNGuidelinesVersion1.2023Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadexGENERALCONSIDERATIONSFORSYSTEMICTHERAPYFORWM/LPLFrailtyassessmentFrailtyassessmentshouldbeconsideredinolderadultsSeeNCCNGuidelinesforOlderAdultOncology.pheresisshouldalsobeconsidered?ScreenforHIVandhepatitisC,asclinicallyindicated.?ScreenforHIVandhepatitisC,asclinicallyindicated.PneumocystisjiroveciPneumocystisjirovecipneumoniaPJP)prophylaxisshouldbeconsideredforpatientsreceivingbendamustine/rituximaborfludarabine/CarfilzomibcanpotentiallycausecardiacCarfilzomibcanpotentiallycausecardiacandpulmonarytoxicity,especiallyinelderlypatients.?Subcutaneousbortezomibisthepreferredmethod?Subcutaneousbortezomibisthepreferredmethodofadministration.Substitutionsreceivedthefirstfulldoseofrituximabbyintravenousinfusion.?Rituximabandhyaluronidasehumaninjectionforsubcutaneousreceivedthefirstfulldoseofrituximabbyintravenousinfusion.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version1.2023,07/06/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.WM/LPL-BOF4PrintedbyMinTangon7/14/20229:44:12AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion1.2023Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadexPRIMARYTHERAPYFORWM/LPLa(Orderofregimensisalphabeticalanddoesnotindicatepreference)ens?Bendamustine/rituximab?Bortezomib/dexamethasone/rituximabb?Ibrutinib±rituximab(category1)Zanubrutinib(category1)ecommendedRegimensamustinefilzomibrituximabdexamethasonezomibrituximabdexamethasoneuximabuximabcyclophosphamidedexamethasoneuximabcyclophosphamideprednisoneaSeeGeneralConsiderationsforSystemicTherapyforWM/LPL(WM/LPL-B1of4).bConsiderforpatientspresentingwithsymptomatichyperviscosity,orinwhomrapidIgMreductionisrequired.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version1.2023,07/06/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.WM/LPL-B2OF4WM/LPL-B3OF4PrintedbyMinTangon7/14/20229:44:12AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllWM/LPL-B3OF4NCCNGuidelinesVersion1.2023Waldenstr?mMacroglobulinemia/LymphoplasmacyticLymphomadexTHERAPYFORPREVIOUSLYTREATEDWM/LPLa(Ordero