华氏巨球蛋白血症淋巴浆细胞淋巴瘤2022.v3（英文）-NCCN肿瘤临床实践指南

NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines®)WaldenströmMacroglobulinemia/LymphoplasmacyticLymphomarsionMayNCCNGuidelinesforPatients®availableat/patientsVersion3.2022,05/02/22©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon6/4/20227:44:25AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion3.2022WaldenströmMacroglobulinemia/LymphoplasmacyticLymphomadex*ShajiK.Kumar,MD/Chair‡ξMayoClinicCancerCenter*NatalieS.Callander,MD/ViceChair‡ξUniversityofWisconsineCancerCenterKehindeAdekola,MD,MSCI‡†RobertH.LurieComprehensiveCancerCenterofNorthwesternUniversityLarryAnderson,Jr.,MD,PhD‡†UTSouthwesternSimmonsComprehensiveCancerCenterMuhamedBaljevic,MD†‡ÞξFred&PamelaBuffettCancerCenterEricaCampagnaro,MD‡UniversityofMichiganRogelCancerCenter*JorgeJ.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‡ÞCityofHopeNationalMedicalCenterCarolAnnHuff,MD†‡TheSidneyKimmelComprehensiveCancerCenteratJohnsHopkinsMalinHultcrantz,MD,PhD‡†MemorialSloanKetteringCancerCenterYubinKang,MD‡†ξDukeCancerInstituteSarahLarson,MD†UCLAJonssonComprehensiveCancerCenterMichaelaLiedtke,MD‡StanfordCancerInstituteThomasMartin,MD‡UCSFHelenDillerFamilyComprehensiveCancerCenterJamesOmelMD¥eDouglasSborov,MD,MSc†‡ÞξHuntsmanCancerInstituteattheUniversityofUtahKennethShain,MD,PhD†MoffittCancerCenterKeithStockerl-Goldstein,MD†ξSitemanCancerCenteratBarnes-JewishHospitalandWashingtonUniversitySchoolofMedicineDonnaWeber,MD†‡ÞTheUniversityofTexasdiMScesPanelDisclosuresξBonemarrowtransplantation¥Patientadvocacy‡Hematology*DiscussionsectionwritingÞInternalmedicinecommittee†MedicaloncologyVersion3.2022,05/02/22©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon6/4/20227:44:25AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion3.2022WaldenströmMacroglobulinemia/LymphoplasmacyticLymphomadexlievesthatthebestmanagementlievesthatthebestmanagementforanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.FindanNCCNMemberInstitution:/home/member-institutions.ofEvidenceandsusAllrecommendationsotherwisedNCategoriesofEvidenceandConsensus.NCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.ofGuidelinesUpdatesrTreatmentWMLPLRelapseWMLPLWHOCriteriaforLymphoplasmacyticLymphomaandWaldenströmMacroglobulinemiaWaldenströmMacroglobulinemiaInternationalWorkshopCriteria(WM/LPL-A)WaldenströmMacroglobulinemia/LymphoplasmacyticLymphomaTherapy(WM/LPL-B)ResponseCriteriaforWM/LPL(WM/LPL-C)TheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatmentAnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualstancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetworkNCCNmakesnorepresentationsorwarrantiesofanykindregardingtheircontentuseorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinanywayTheNCCNbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.©2021.Version3.2022,05/02/22©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESVersion3.2022,05/02/22©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon6/4/20227:44:25AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion3.2022WaldenströmMacroglobulinemia/LymphoplasmacyticLymphomadexoftheNCCNGuidelinesforWMLPLfromVersioninclude•TheDiscussionsectionhasbeenupdatedtoreflectchangesinthealgorithm.UpdatesinVersion2.2022oftheNCCNGuidelinesforWM/LPLfromVersion1.2022include:WM/LPL-B3of4•TherapyforPreviouslyTreatedWM/LPLpThefollowingwasaddedtoOtherRecommendedRegimens:◊Venetoclax(category2A)WM/LPL-B4of4•Referenceadded:CastilloJJ,AllanJN,SiddiqiT,AdvaniRH,MeidK,LeventoffC,etal.VenetoclaxinPreviouslyTreatedWaldenströmMacroglobulinemia.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.Arandomizedphase3trialofzanubrutinibvsibrutinibinsymptomaticWaldenströmmacroglobulinemia: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.ngwithsuspecteddiseaserelatedtoperipheralneuropathyspeofcasesandchainaloneandnonsecretorysubtypesthoughmakesup<5%ofallLPLs.TheMacroglobulinemia(WM/LPL-A).NCCNGuidelinesVersion3.2022WaldenströmMacroglobulinemia/LymphoplasmacyticLymphomadexDIAGNOSISINDICATIONSFORDIAGNOSISINDICATIONSFORTREATMENTtaintainCircumstances•HematopathologywithatleastonereviewwithatleastoneCDCDsIgM+;CD5,CD10,inCD23indMYDwildtypeoccursin<10%ofpatientsandshouldnotbeusedtodMYDwildtypeoccursin<10%ofpatientsandshouldnotbeusedtoexcludediagnosisofWMifothercriteriaaremet.eStudieshaveshownthatmutationsineStudieshaveshownthatmutationsinthisgenearefoundinupto40%ofbSeeWHOCriteriaforLymphoplasmacyticLymphomaandWaldenströmfConsiderinpatientswithsuspectedcryoglobulinemia.patientswithWMfConsiderinpatientswithsuspectedcryoglobulinemia.treatmentofnon-IgMLPLsparallelsthatofIgM-secretingLPLs,buttheseareuleoutamyloidosisinpatientspresentingwithnephroticsyndromeorlesslikelyuleoutamyloidosisinpatientspresentingwithnephroticsyndromeorunexplainedcardiacproblems.iConfirmsymptomsarenotrelatedtoorcausedbycomorbidities.relatedunexplainedcardiacproblems.iConfirmsymptomsarenotrelatedtoorcausedbycomorbidities.myeloma.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.WM/LPL-1Version3.2022,05/02/22©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.derpreviouslyusedsifwelltoleratedanddresponselpternativetherapylpternativetherapylpformationseeNCCNGuidelinesforphomaPrintedbyMinTangonderpreviouslyusedsifwelltoleratedanddresponselpternativetherapylpternativetherapylpformationseeNCCNGuidelinesforphomaNCCNGuidelinesVersion3.2022WaldenströmMacroglobulinemia/LymphoplasmacyticLymphomadexPRIMARYTREATMENTjrrsymptomaticrialIftransformation,seeNCCNGuidelinesforB-CellLymphomas,FollicularLymphomaRELAPSERELAPSE•Completemresponsem•VerygoodpartialmresponsemialminorialminormdiseasemdiseasemObserven,ountilasemoountilivediseasemerrituximabforerapyomsIfpersistentomsjIntentoftherapyshouldbebasedonpalliationofsymptoms,notnecessarilylevelsofIgMunlessthepatientisexhibitingevidenceofsymptomatichyperviscosity.lSeeWaldenströmMacroglobulinemia/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-2Version3.2022,05/02/22©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.*Sumoftotalpointsintable1ohaveplasmacyticdifferentiationpermission*Sumoftotalpointsintable1ohaveplasmacyticdifferentiationpermissionfromSwerdlowSHCampoEHarrisNLetalWorldHealthOrganizationClassificationofTumoursofHaematopoieticandLymphoiduesrevisedtheditionIARCLyonNCCNGuidelinesVersion3.2022WaldenströmMacroglobulinemia/LymphoplasmacyticLymphomadexWHOCRITERIAFORLYMPHOPLASMACYTICLYMPHOMAANDWALDENSTRÖMMACROGLOBULINEMIA•Waldenströmmacroglobulinemia:pLymphoplasmacyticlymphomawithbonemarrowinvolvementandIgMmonoclonalgammopathyofanyconcentrationAdaptedwithpermission.OwenRG,TreonSP,Al-KatibA,etal.ClinicopathologicalDefinitionofWaldenstrom'sMacroglobulinemia:ConsensusPanelRecommendationsfromtheSecondInternationalWorkshoponWaldenstom'sMacroglobulinemia.SeminOncol.2003;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-AVersion3.2022,05/02/22©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.candidates.beforetreatmentwithrituximaborofatumumabforasymptomaticWaldenstrmmacroglobulinemiapatientswithanIgM0mg/dLmayalsobeheldinpatientswithelevatedserumIgMlevelsforinitialtreatmentcycles.BloodwarmersshouldbeusedforapheresisifProphylacticantiviraltherapywithentecavirisrecommendedforanypatientwhoisHBsAg-positiveandreceivinganti-CD20therapy.cyclophosphamide/rituximab.tiviraltherapyispreferredhoweverifthereisaconcurrenthighlevelhepatitisBsurfaceantibodythesepatientsmaybeIfcandidatesforhematopoieticcelltransplantation(HCT)NCCNGuidelinesVersion3.2022WaldenströmMacroglobulinemia/LymphoplasmacyticLymphomadexGENERALCONSIDERATIONSFORSYSTEMICTHERAPYFORWM/LPLFrailtyassessmentFrailtyassessmentshouldbeconsideredinolderadultsSeeNCCNGuidelinesforOlderAdultOncology.pheresisshouldalsobeconsideredcryoprecipitateorcryoglobulinarepresent.TestforTestforhepatitisBbeforestartingcarfilzomib,rituximab,orofatumumab.PneumocystisjiroveciPneumocystisjirovecipneumoniaPJP)prophylaxisshouldbeconsideredforpatientsreceivingbendamustine/rituximaborfludarabine/CarfilzomibcanpotentiallycausecardiacCarfilzomibcanpotentiallycausecardiacandpulmonarytoxicity,especiallyinelderlypatients.•Subcutaneousbortezomibisthepreferredmethod•Subcutaneousbortezomibisthepreferredmethodofadministration.Substitutionsreceivedthefirstfulldoseofrituximabbyintravenousinfusion.•Rituximabandhyaluronidasehumaninjectionforsubcutaneousreceivedthefirstfulldoseofrituximabbyintravenousinfusion.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version3.2022,05/02/22©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.WM/LPL-BOF4PrintedbyMinTangon6/4/20227:44:25AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion3.2022WaldenströmMacroglobulinemia/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/AMLinpatientswithWaldenströmmacroglobulinemia.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version3.2022,05/02/22©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.WM/LPL-B2OF4WM/LPL-B3OF4PrintedbyMinTangon6/4/20227:44:25AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllWM/LPL-B3OF4NCCNGuidelinesVersion3.2022WaldenströmMacroglobulinemia/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/AMLinpatientswithWaldenströmmacroglobulinemia.dOfatumumabmaybeusedforrituximab-intolerantindividualsasasingleagentorincombinationtherapyanywherethatrituximabisgiven.Whileofatumumabisnolongercommerciallyavailable,itmaybeobtainedforclinicaluse.eShouldideallybeundertakeninthecontextofaclinicaltrial.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version3.2022,05/02/22©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon6/4/20227:44:25AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.NCCNGuidelinesVersion3.2022WaldenströmMacroglobulinemia/LymphoplasmacyticLymphomadexSUGGESTEDREFERENCESCastilloJJ,AllanJN,SiddiqiT,AdvaniRH,MeidK,LeventoffC,etal.VenetoclaxinPreviouslyTreatedWaldenströmMacroglobulinemia.JClinOncol.2021Nov18:JCO2101194.ChesonBD,RummelMJ.Bendamustine:rebirthofanolddrug.JClinOncol2009;27:1492-1501.osAKyrtsonisMCetalPrimarytreatmentenstromsmacroglobulinemiawithdexamethasonerituximabandcyclophosphamide.JClinOncol2007;25:3344-3349.DimopoulosMA,AnagnostopoulosA,ZervasC,etal.PredictivefactorsforresponsetorituximabinWaldenstrom'smacroglobulinemia.ClinLymphoma2005;5:270-272.mopoulosMAGertzMAKastritisEetalUpdateontreatmentomtheFourthInternationalWorkshoponWaldenstromsMacroglobulinemia.JClinOncol2009;27:120-126.eatmentofWaldenstromsmacroglobulinemiawithrituximab.JClinOncol2002;20:2327-2333.astritisEOwenRetalTreatmentrecommendationsforpatientswithWaldenstromsmacroglobulinemiaWMandrelateddisorders:consensusfromtheSeventhInternationalWorkshoponWM.Blood2014;124:1404-14