慢性髓系白血病2023.v1l-NCCN（英文版）

NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines?)ChronicMyeloidLeukemiatientsavailableatwwwnccnorgpatientsVersion1.2023,08/05/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon8/6/20227:06:29AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.idLeukemiadex*NeilP.Shah,MD,PhD/Chair?UCSFHelenDillerFamilyComprehensiveCancerCenter*RaviBhatia,MD/Vice-Chair?O'NealComprehensiveCancerCenteratUABJessicaK.Altman,MD?RobertH.LurieComprehensiveCancerCenterofNorthwesternUniversityMariaAmaya,MD,PhD?UniversityofColoradoCancerCenterKebedeH.Begna,MD?MayoClinicCancerCenterEllinBerman,MD??TMemorialSloanKetteringCancerCenterRobertH.Collins,Jr.,MD?UTSouthwesternSimmonsComprehensiveCancerCenterPeterT.Curtin,MD??ξCityofHopeNationalMedicalCenterDanielJ.DeAngelo,MD,PhD??Dana-Farber/BrighamandWomen’senterJasonGotlib,MD,MS??StanfordCancerInstituteGabrielaHobbs,MD??MassachusettsGeneralHospitalCancerCenteresPanelDisclosuresHagopM.Kantarjian,MD?TheUniversityofTexasLoriManess,MD?FredandPamelaBuffettCancerCenterMonicaMead,MD?UCLAJonssonComprehensiveCancerCenterLelandMetheny,MD?ξCaseComprehensiveCancerCenterUniversityHospitalsSeidmanCancerCenterandClevelandClinicTaussigCancerInstituteSanjayMohan,MD,MSCI?Vanderbilt-IngramCancerCenterJosephO.Moore,MD?DukeCancerInstituteVivianOehler,MD?FredHutchinsonCancerResearchCenter/SeattleCancerCareAllianceKeithPratz,MD?AbramsonCancerCenterheUniversityofPennsylvaniaIskraPusic,MD,MSCI?SitemanCancerCenteratBarnes-JewishHospitalandWashingtonUniversitySchoolofMedicineMichalG.Rose,MD?YaleCancerCenter/SmilowCancerHospitalB.DouglasSmith,MD?TTheSidneyKimmelComprehensiveCancerCenteratJohnsHopkinsKendraL.Sweet,MD,MS??TMoffittCancerCenterMosheTalpaz,MD?UniversityofMichiganRogelCancerCenterTiffanyN.Tanaka,MD?UCSanDiegoMooresCancerCenterJamesThompson,MD,MS?RoswellParkComprehensiveCancerCenterJenniferVaughn,MD,MSPH?TheOhioStateUniversityComprehensiveCancerCenter-JamesCancerHospitalandSoloveResearchInstituteJeannaWelborn,MD?UCDavisComprehensiveCancerCenterDavidT.Yang,MD≠UniversityofWisconsineCancerCenterξ?T?≠BonemarrowtransplantationHematology/HematologyoncologyInternalmedicineMedicaloncology*DiscussionSectionWritingCommitteeVersion1.2023,08/05/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.MyeloidLeukemiaPanelMembersryofGuidelinesUpdatesrkupCMLMLCMLEarlyTreatmentResponseMilestonesClinicalConsiderationsandRecommendationsCMLMyeloidLeukemiaPanelMembersryofGuidelinesUpdatesrkupCMLMLCMLEarlyTreatmentResponseMilestonesClinicalConsiderationsandRecommendationsCMLvancedPhaseCMLCMLTreatmentRecommendationsBasedonBCRABLMutationProfile(CML-5)eneicHematopoieticCellTransplantationCMLRiskCalculationTable(CML-A)DefinitionsofAcceleratedPhaseandBlastPhase(CML-B)ManagementofCMLDuringPregnancy(CML-C)CriteriaforResponseandRelapse(CML-D)MonitoringResponsetoTKITherapyandMutationalAnalysis(CML-E)DiscontinuationofTKITherapy(CML-F)ManagementofBosutinibToxicity(CML-G1of9)ManagementofDasatinibToxicity(CML-G2of9)ManagementofImatinibToxicity(CML-G3of9)ManagementofNilotinibToxicity(CML-G4of9)ManagementofOmacetaxineToxicity(CML-G5of9)ManagementofPonatinibToxicity(CML-G6of9)ManagementofAsciminibToxicity(CML-G7of9)teractionsofTKIsCMLGofAbbreviations(ABBR-1)idLeukemiadexlievesthatthebestmanagementforanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.FindanNCCNMemberInstitution:/home/member-institutions.ofEvidenceanddationsotherwisedNCategoriesofEvidenceandConsensus.NCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.TheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatment.AnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualclinicaltancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetworkNCCNmakesnorepresentationsorwarrantiesofanykindregardingtheircontentuseorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinanyway.TheNCCNbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.?2022.Version1.2023,08/05/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESVersion1.2023,08/05/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon8/6/20227:06:29AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.idLeukemiadexrsionoftheNCCNGuidelinesforChronicMyeloidLeukemiafromVersionincludeGeneral?BCR-ABLreplacedwithBCR::ABLCML-2?Footnotehadded:Limitedavailableevidencefromsmallcohortstudiessuggeststhatinitiationoffirst-lineTKIs(bosutinib,dasatinib,ornilotinib)atlowerdoses(tominimizetreatment-relatedadverseevents)anddosereduction(withclosemonitoring)inpatientswhoachieveoptimalresponsesareappropriatestrategiestoreducetheriskoflong-termtoxicities.However,theminimumeffectivedoseoroptimalde-escalationofTKI(bosutinib,dasatinib,ornilotinib)hasnotyetbeenestablishedinprospectiverandomizedclinicaltrials.SeetheDiscussionsectionforDoseModificationsofTKITherapy.CML-3?Increaseimatinibdosetoamaxof800mgremovedasarecommendationforpossibleTKIresistanceat3monthsand12months.(Yellowcolor)?MutationalstatusclarifiedwithadditionofBCR::ABL1kinasedomain.?Footnoteoadded:ConsidermyeloidmutationpaneltoidentifyBCR::ABL1–independentresistancemutationsinpatientswithnoBCR::ABL1kinasedomainmutations.CML-4?Acceleratedphasep1GTKI(imatinib)movedtoUsefulincertaincircumstanceswiththefollowingqualifier:?if2Gor3GTKIiscontraindicated?BlastphasepInductionchemotherapy+TKInotedaspreferredpTKI±steroidsnotedasUsefulincertaincircumstanceswiththefollowingqualifier:?ifnotacandidateforinductionchemotherapyCML-4A?Footnoteuadded:TKI(aloneorincombinationwithminimalchemotherapyorsteroids)islesseffectiveinBP-CMLcomparedtoPh-positiveALL.InterphaseFISHforthedetectionofBCR::ABL1transcriptonbloodgranulocytesisrecommendedtodifferentiatebetweendenovoBP-CMLanddenovoPh-positiveALL.?Footnotewmodifiedwithadditionofsentence:OmacetaxineisindicatedforthetreatmentofacceleratedphaseCMLthatisresistantand/orintoleranttotwoormoreTKIs.?Footnotexadded:2Gor3GTKIispreferred.Considerimatinibforpatientswithcontraindicationsto2Gor3GTKI.CML-5?Bullets1and3:kinasedomainaddedafterBCR::ABL1?Asciminib:A337TandP465Saddedascontraindicatedmutations?Footnotezrevisedtoincludethefollowing:BCR::ABL35INShasbeenreportedinpatientswhodonotrespondtoimatinib;however,therearenotenoughdatatoconfirmthat2GTKIscouldovercomethisresistance(BermanE,etal.LeukRes2016;49:108-112).SeeDiscussion.?Thefollowingsentencewasremovedfromfootnotezandaddedtofootnotebb:Therearecompoundmutationsthatcancauseresistancetoponatinib,butthoseareuncommonfollowingtreatmentwithbosutinib,dasatinib,ornilotinib.?Footnotebbmodified:PonatinibisathepreferredtreatmentoptionforpatientswithaT315Imutation.Itisalsoatreatmentoptionforand/orCP-CMLwithresistanceorintolerancetoatleasttwopriorTKIsorforpatientswithAP-CMLorBP-CMLforwhomnootherTKIisindicated.Therearecompoundmutationsthatcancauseresistancetoponatinib,butthoseareuncommonfollowingtreatmentwithbosutinib,dasatinib,ornilotinib.?Footnoteccmodified:OmacetaxineisatreatmentoptionforpatientswithchronicoracceleratedphaseCMLdiseasethatisresistantand/orintoleranttotwoormoreTKIs.CML-G8of9?Druginteractionsaddedforasciminib(alsoappliesforCML-G9of9)ABBR1breviationsatitisBpanelcPrintedbyMinTangon8/6/20227:06:29AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.atitisBpanelcidLeukemiadexWORKUPCLINICALPRESENTATIONADDITIONALEVALUATION?H&P,includingspleensizebypalpation(cmbelowcostalmargin)?CBCwithdifferential?Chemistryprofile?Bonemarrowaspirateandogeneticevaluationabiopsyogeneticevaluationa?QuantitativeRT-PCR(qPCR)forBCRABL1(blood)busingforBCRABL1(blood)bPh-positiveorBCR::ABL1cceleratedccelerated(AP-CML)dAdvancedBlastphaseBlastphasePh-negativeandBCR::ABL1negativeEvaluatefordiseasesotherthanCML(SeeNCCNGuidelinesforMyeloproliferativeNeoplasms)Determineriskscore(SeeRiskCalculationTableCML-A)SeeCML-2estingifngallogeneicestingifngallogeneice?ConsidereSeeCML-4aBonemarrowevaluationshouldbedonefortheinitialworkup,toprovidemorphologicreview,andalsotodetectchromosomalabnormalitiesinadditiontothePhchromosome.Fluorescenceinsituhybridization(FISH)canbeusedifcytogeneticevaluationisnotpossible.bConsiderqualitativeRT-PCRforthedetectionofatypicalBCR::ABL1transcripts.SeeDiscussion.Referraltocenterswithexpertiseinthemanagementofrarehematologicmalignanciesisrecommended.cHepatitisBvirusreactivationhasbeenreportedinpatientsreceivingtyrosinekinaseinhibitor(TKI)therapy.However,itisnotalwayspossibletoreliablyestimatethefrequencyorestablisharelationshiptodrugexposurebecausetheseincidencesarereportedvoluntarilyfromapopulationofuncertainsize.dSeeDefinitionsofAcceleratedPhaseandBlastPhase(CML-B).eConsidermyeloidmutationpanelforpatientswithacceleratedphaseorblastphase.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version1.2023,08/05/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.CML-1PrintedbyMinTangon8/6/20227:06:29AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.idLeukemiadexCLINICALPRESENTATIONPRIMARYTREATMENTf,g,hPreferredregimensQD[category1])iFirst-generation(1G)TKI(ImatinibQD[category1])iponseponseSecondgenerationGTKIalphabeticalalculationconsiderationsindependentofriskscore?ComorbiditiesileofonsCMLkl(Bosutinib400mgQD[category1]orDasatinib100mgQD[category1]or lotinibir300mgtyrosinekinaseClinicaltyrosinekinaseIIibledrug2GTKIibledrugeorhighscoreeRiskCalculationeorhighscoreeRiskCalculationponseientpreference ientpreference onsCMLkonsCMLklTKIImatinibTKIImatinibmgQDijorClinicaltrialfIftreatmentisneededduringpregnancy,itispreferabletoinitiatetreatmentwithinterferons(interferonalfa-2aorpeginterferonalfa-2a).Interferonalfa-2a/2bandpeginterferonalfa-2bhavebeendiscontinued.Peginterferonalfa-2amaybesubstitutedforotherinterferonpreparations.TKItherapy,particularlyduringthefirsttrimester,shouldbeavoided.SeeManagementofCMLDuringPregnancy(CML-C).gBasedonfollow-updatafromtheBFORE,DASISION,andENESTndtrials,2GTKIs(bosutinib,dasatinib,ornilotinib)arepreferredforpatientswithanintermediate-orhigh-riskscore.2GTKIsshouldalsobeconsideredforspecificsubgroups(basedontheassessmentoftreatmentgoalsandbenefit/risks),forexample,youngerpatientswhoareinterestedinultimatelydiscontinuingtreatmentandespeciallyyoungpatientsassignedfemaleatbirthwhosegoalistoachieveadeepandrapidmolecularresponseandeventualdiscontinuationofTKItherapyforfamilyplanningpurposes.hLimitedavailableevidencefromsmallcohortstudiessuggeststhatinitiationoffirst-lineTKIs(bosutinib,dasatinib,ornilotinib)atlowerdoses(tominimizetreatment-relatedadverseevents)anddosereduction(withclosemonitoring)inpatientswhoachieveoptimalresponsesareappropriatestrategiestoreducetheriskoflong-termtoxicities.However,theminimumeffectivedoseoroptimalde-escalationofTKI(bosutinib,dasatinib,ornilotinib)hasnotyetbeenestablishedinprospectiverandomizedclinicaltrials.SeetheDiscussionsectionforDoseModificationsofTKITherapy(MS-17).iInnovatorandgenericdrugsapprovedbytheregulatoryauthoritiesbasedonpharmacokineticequivalencecanbeusedinterchangeably.AnFDA-approvedgenericversionisanappropriatesubstituteforaninnovatordrug(imatinib).GenericversionsofotherTKIsarelikelytobemarketedinthenearfuture.jImatinibmaybepreferredforolderpatientswithcomorbiditiessuchascardiovasculardisease.kSeeCriteriaforResponseandRelapse(CML-D).lSeeMonitoringResponsetoTKITherapyandMutationalAnalysis(CML-E).Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version1.2023,08/05/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.CML-2PrintedbyMinTangon8/6/20227:06:29AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.idLeukemiadexEARLYTREATMENTRESPONSEMILESTONESk,lCRABLISshsm>10%nYELLOWYELLOW≤0.1%CLINICALCONSIDERATIONSRECOMMENDATIONSesistantConsiderBCRABLkinasedomainmutationalConsiderBCRABLkinasedomainmutationalanalysisoSwitchtoalternateTKICMLandevaluateforallogeneicHCTYELLOWConsiderBCRABLkinasedomainmutationalConsiderBCRABLkinasedomainmutationalanalysisoConsiderbonemarrowcytogeneticanalysistoassessforMCyRatmoorCCyRatmoContinuesameTKIotherthanimatinibCMLContinuesameTKIotherthanimatinibCMLGpandConsiderevaluationforallogeneicHCTensitive?Iftreatmentgoalislong-termsurvival:≤1%optimal?Iftreatmentgoalistreatment-freeremission:≤0.1%optimal?Ifoptimal:continuesameTKI?Ifnotoptimal:shareddecisionensitiveonitorresponseCMLEandsideeffectsContinuesameTKI(CML-G)skSeeCriteriaforResponseandRelapse(CML-D).lSeeMonitoringResponsetoTKITherapyandMutationalAnalysis(CML-E).mBCR::ABL1≤0.1%at12monthsisassociatedwithaverylowprobabilityofsubsequentlossofresponseandahighlikelihoodofachievingasubsequentdeepmolecularresponse(DMRMR4.0;≤0.01%BCR::ABL1IS),whichisaprerequisiteforatrialoftreatment-freeremission(TFR).nPatientswithBCR::ABL1onlyslightly>10%at3monthsand/orwithasteepdeclinefrombaselinemayachieve<10%at6monthsandhavegenerallyfavorableoutcomes.Therefore,itisimportanttointerpretthevalueat3monthsinthiscontextbeforemakingdrasticchangestothetreatmentstrategy.oConsidermyeloidmutationpaneltoidentifyBCR::ABL1–independentresistancemutationsinpatientswithnoBCR::ABL1kinasedomainmutations.pAchievementofresponsemilestonesmustbeinterpretedwithintheclinicalcontext.Patientswithmorethan50%reductioncomparedtobaselineorminimallyabovethe10%cutoffcancontinuethesamedoseofdasatinib,nilotinib,orbosutinibforanother3months.Continuationofimatinib400mgisnotrecommended.qSwitchingfromimatinibtoa2GTKIimprovesresponse,butisassociatedwithincreasedtoxicity.rConsiderreferraltoaspecializedCMLcenterand/orenrollmentinaclinicaltrial.sDiscontinuationofTKIwithcarefulmonitoringisfeasibleinselectedpatients.SeeDiscontinuationofTKITherapy(CML-F).Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version1.2023,08/05/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.CML-3TKIixCMLG+steroidsAllogeneicAllogeneicAllogeneicrapyincircumstancesPrintedbyMinTangon8/6/20227:06:29AM.Forpersonaluseonly.NotapprovedTKIixCMLG+steroidsAllogeneicAllogeneicAllogeneicrapyincircumstancesidLeukemiadexCLINICALPRESENTATIONdvanced?Selection?SelectionofTKIisbasedonpriortherapyand/orBCR::ABL1mutationproile.?CNSinvolvementhasbeendescribedinBP-CML.LumbarpunctureandCNSprophylaxisisrecommendedforlymphoidblastphase.?DiseaseprogressiontoadvancedphasewhileonTKItherapyhasworseprognosisthandenovoadvancedphaseCML.dt?EvaluationdtFootnotesonCMLATREATMENTfAcceleratedphased(AP-CML)ensensGorthirdgeneration(3G)TKIlphabeticalorderBosutiniborincircumstancesDasatiniborlphabeticalorderBosutiniborincircumstancesrialLLtypeinductionchemotherapy+TKIi,x(CML-G)+TKIi,x(CML-G)ototacandidateforinductionrapyphased,u(BP-CML)rialensLLtypeinductionchemotherapy+TKIi,x(CML-G)LincircumstancesotacandidateincircumstancesotacandidateforinductionNote:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.CML-4Version1.2023,08/05/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon8/6/20227:06:29AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.idLeukemiadexdSeeDefinitionsofAccelerateddSeeDefinitionsofAcceleratedPhaseandBlastPhase(CML-B).fIftreatmentisneededduringpregnancy,itispreferabletoinitiatetreatmentwithinterferons(interferonalfa-2aorpeginterferonalfa-2a).Interferonalfa-2a/2bandpeginterferonalfa-2bhavebeendiscontinued.Peginterferonalfa-2amaybesubstitutedforotherinterferonpreparations.TKItherapy,particularlyduringthefirsttrimester,shouldbeavoided.SeeManagementofCMLDuringPregnancy(CML-C).iInnovatorandgenericdrugsapprovedbytheregulatoryauthoritiesbasedonpharmacokineticequivalencecanbeusedinterchangeably.AnFDA-approvedgenericversionisanappropriatesubstituteforaninnovatordrug(imatinib).GenericversionsofotherTKIsarelikelytobemarketedinthenearfuture.tThepresenceofmajorrouteadditionalchromosomalabnormalities(ACAs)inPh-positivecells(trisomy8,isochromosome17q,secondPh,andtrisomy19)mayhaveanegativeprognosticimpactonsurvival.PatientswhopresentwithacceleratedphaseatdiagnosisshouldbetreatedwithaTKI,followedbyevaluationforallogeneicHCT,basedonresponsetotherapy.ConsiderevaluationforallogeneicHCTifresponsemilestonesarenotachievedat3,6,and12monthsasoutlinedonCML-3.uTKI(aloneorincombinationwithminimalchemotherapyorsteroids)islesseffectiveinBP-CMLcomparedtoPh-positiveALL.InterphaseFISHforthedetectionofBCR::ABL1transcriptonbloodgranulocytesisrecommendedtodifferentiatebetweendenovoBP-CMLanddenovoPh-positiveALL.vImatinibisnotrecommendedforpatientswithdiseaseprogressiononpriorTKItherapy.wOmacetaxineisindicatedforthetreatmentofacceleratedphaseCMLthatisresistantand/orintoleranttotwoormoreTKIs.OmacetaxineisatreatmentoptionforpatientswithdiseaseprogressiontoAP-CML.OmacetaxineisnotatreatmentoptionforpatientswhopresentwithAP-CML.x2Gor3GTKIispreferred.Considerimatinibforpatientswithcontraindicationsto2Gor3GTKI.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.CML-4AVersion1.2023,08/05/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon8/6/20227:06:29AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.idLeukemiadexTREATMENTRECOMMENDATIONSBASEDONBCR::ABL1MUTATIONPROFILE?Patientswithdiseaseresistanttoprimarytreatmentwithimatinibshouldbetreatedwithbosutinib,dasatinib,o