华氏巨球蛋白血症淋巴浆细胞淋巴瘤2023.v1-NCCN（英文版）

NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines®)WaldenströmMacroglobulinemia/LymphoplasmacyticLymphomarsionJulyNCCNGuidelinesforPatients®availableat/patientsVersion1.2023,07/06/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon7/14/20229:44:12AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion1.2023WaldenströmMacroglobulinemia/LymphoplasmacyticLymphomadex*ShajiK.Kumar,MD/Chair‡ξMayoClinicCancerCenter*NatalieS.Callander,MD/ViceChair‡ξUniversityofWisconsineCancerCenterKehindeAdekola,MD,MSCI‡†RobertH.LurieComprehensiveCancerCenterofNorthwesternUniversityLarryD.Anderson,Jr.,MD,PhD‡†UTSouthwesternSimmonsComprehensiveCancerCenterMuhamedBaljevic,MD†‡ÞξVanderbilt-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‡ÞCityofHopeNationalMedicalCenterCarolAnnHuff,MD†‡TheSidneyKimmelComprehensiveCancerCenteratJohnsHopkinsMalinHultcrantz,MD,PhD‡†MemorialSloanKetteringCancerCenterYubinKang,MD‡†ξDukeCancerInstituteSarahLarson,MD†UCLAJonssonComprehensiveCancerCenterHansLee,MD†‡TheUniversityofTexasMichaelaLiedtke,MD‡StanfordCancerInstituteThomasMartin,MD‡UCSFHelenDillerFamilyComprehensiveCancerCenterJamesOmelMD¥eAaronRosenberg,MD†‡ξmprehensiveCancerCenterDouglasSborov,MD,MSc†‡ÞξHuntsmanCancerInstituteattheUniversityofUtahKeithStockerl-Goldstein,MD†ξSitemanCancerCenteratBarnes-JewishHospitalandWashingtonUniversitySchoolofMedicineJasonValent,MD†‡CaseComprehensiveCancerCenter/UniversityHospitalsSeidmanCancerCenterandClevelandClinicTaussignstitutediMScesPanelDisclosuresξBonemarrowtransplantation¥Patientadvocacy‡Hematology*DiscussionsectionwritingÞInternalmedicinecommittee†MedicaloncologyVersion1.2023,07/06/22©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon7/14/20229:44:12AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion1.2023WaldenströmMacroglobulinemia/LymphoplasmacyticLymphomadexlievesthatthebestmanagementlievesthatthebestmanagementforanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.FindanNCCNMemberInstitution:/home/member-institutions.ofEvidenceandsusAllrecommendationsotherwisedNCategoriesofEvidenceandConsensus.NCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.ofGuidelinesUpdatespWMLPLAsymptomaticorMinimallySymptomatic(WM/LPL-2)RelapseWMLPLWHOCriteriaforLymphoplasmacyticLymphomaandWaldenströmMacroglobulinemiaWaldenströmMacroglobulinemiaInternationalWorkshopCriteria(WM/LPL-A)WaldenströmMacroglobulinemia/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.NCCNGuidelinesVersion1.2023WaldenströmMacroglobulinemia/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.NCCNGuidelinesVersion1.2023WaldenströmMacroglobulinemia/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.ofcasesandsNCCNGuidelinesVersion1.2023WaldenströmMacroglobulinemia/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.NCCNGuidelinesVersion1.2023WaldenströmMacroglobulinemia/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.NCCNGuidelinesVersion1.2023WaldenströmMacroglobulinemia/LymphoplasmacyticLymphomadexPRIMARYTREATMENToRELAPSEConsiderpreviouslyusedObserves,tuntilObserves,tuntildresponseqvixeddurationotherapyixeddurationotherapyrrsymptomatichBTKmensrialionternativetherapyquonorxicityCNdelinesorBCellFolliculartionseeCNdelinesorBCellFollicularIfpersistentsymptomsdiseaser(WM/LPL-B).qSeeWaldenströmMacroglobulinemia/(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*Sumoftotalpointsintable1ohaveplasmacyticdifferentiationpermissionfromSwerdlowSHCampoEHarrisNLetalWorldHealthOrganizationClassificationofTumoursofHaematopoieticandLymphoiduesrevisedtheditionIARCLyonNCCNGuidelinesVersion1.2023WaldenströmMacroglobulinemia/LymphoplasmacyticLymphomadexWHOCRITERIAFORLYMPHOPLASMACYTICLYMPHOMAANDWALDENSTRÖMMACROGLOBULINEMIA•Waldenströmmacroglobulinemia:pLymphoplasmacyticlymphomawithbonemarrowinvolvementandIgMmonoclonalgammopathyofanyconcentrationAdaptedwithpermission.OwenRG,TreonSP,Al-KatibA,etal.ClinicopathologicalDefinitionofWaldenstrom'sMacroglobulinemia:ConsensusPanelRecommendationsfromtheSecondInternationalWorkshoponWaldenstom'sMacroglobulinemia.SeminOncol2003;30:110-115.WALDENSTRÖMMACROGLOBULINEMIAINTERNATIONALWORKSHOPCRITERIAProposedCriteriafortheDiagnosisofWaldenströmMacroglobulinemia•IgMmonoclonalgammopathyofanyconcentration•Bonemarrowinfiltrationbysmalllymphocytes,plasmacytoidcells,andplasmacells•Diffuse,interstitial,ornodularpatternofbonemarrowinfiltration•CD19+,CD20+,sIgM+;CD5,CD10,CD23canbeexpressedinsomecasesofWaldenströmmacroglobulinemiaanddoesnotexcludediagnosis.ReprintedwithpermissionfromElsevierOwenRGDevelopingdiagnosticcriteriainWaldenstrmsmacroglobulinemiaSeminOncol2003;30:196-200.REVISEDIPSSWALDENSTRÖMMACROGLOBULINEMIASCORINGSYSTEMriteriafortheDiagnosisofWaldenstrmMacroglobulinemiaonlyatthetimeofinitialtreatmentprognosticationTable1Age<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.NCCNGuidelinesVersion1.2023WaldenströmMacroglobulinemia/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.NCCNGuidelinesVersion1.2023WaldenströmMacroglobulinemia/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-B3OF4NCCNGuidelinesVersion1.2023WaldenströmMacroglobulinemia/LymphoplasmacyticLymphomadexTHERAPYFORPREVIOUSLYTREATEDWM/LPLa(Ordero