Association of Northern California Oncologists Hematologic ...Leukemias, Lymphomas, and Myeloma...
Transcript of Association of Northern California Oncologists Hematologic ...Leukemias, Lymphomas, and Myeloma...
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AssociationofNorthernCaliforniaOncologists
HematologicMalignanciesUpdates:Leukemias,Lymphomas,andMyeloma
Chair:JosephTuscano,MDdeLeuze EndowedProfessorofMedicine
UniversityofCalifornia,DavisCancerCenter
PanelMembers
• GabrielMannis,MD-- AssistantProfessorBloodandMarrowTransplant,UniversityofCalifornia,SanFrancisco
• JeffreyWolf,MD– ProfessorofMedicine,UniversityofCalifornia,SanFrancisco
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Case1• 44yo womanwithnosignificantPMHpresentstotheEDwith1monthof
fatigue,indigestionandprogressiveDOE;whileintheEDpatientcomplainedof15minutesofblurryvisioninherLeye
• Examwasunremarkablewithnobruising,splenomegalyorlymphadenopathy;visualfieldwithoutdeficituponexamination
• Labswereremarkableforthefollowing:
Lab ValueWBC 145K/mm3
Hgb 8 g/dLPlt 77K/mm3
Blasts 54%ANC 16K/mm3
Lab ValuePotassium 3.4mmol/LCreatinine 0.61 mg/dL
LDH 1700U/LUricAcid 3.4mg/dLD-Dimer 900ng/mL
• Patientundergoesleukapheresis andisstartedonHydroxyurea
• BMBx iscompletedandaspiratereviewrevealsamarkedlyhypercellularmarrow(90%)diffuselyinvolvedwithmyeloblasts (70%)• Flowcytometryconfirmsblastsexpressmyeloidmarkers;CD33is
positive• DiagnosisofAMLisconfirmed
• TTEshowsanormalEF
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Case1• Whatregimenshouldbeconsideredforthispatient(ECOG=0)basedonthe
availableinformation?
A. 7+3
B. 7+3+Gemtuzumab ozogamicin
C. None,awaitmolecularstudiesandcytogenetics
D. Daunorubicin andCytarabine liposome
E. 7+3+Midostaurin
Case1
WhatbenefitisgainedfromtheadditionofMidostaurin inFLT3mutatedAML?
A. ImprovedOverallSurvivalandEventFreeSurvival
B. DecreasedneedforallogeneicHCTinCR1
C. Lesstoxicity
D. ImprovedCRrate
E. Decreasedblastcount
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Case1
• Hercoursewasgenerallyuncomplicatedbarringneutropenicfeverandmucositis
• NextGenerationSequencingMyeloidPanelreturnedrevealingonlyFLT3-ITDandNRASmutations
• Day21BMBx wascompletedandrevealedacellularmarrow(25%)withincreasedblasts(35%)• Cytogenetics46XX
Case1
Whatregimenshouldbechosenforre-induction?
A. 7+3+Midostaurin
B. ClinicalTrial
C. FLAG-IDA
D. 7+3
E. MEC
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Case1
• Sheisre-inducedwith7+3+Midostaurin,againwithhercoursebeinglargelyuncomplicated
• BMTwasconsultedandbeganworkupforpotentialtransplant
• BMBx onDay60showedacellularmarrow(20%)withincreasedblasts(15%),countswerenotrecovered• Cytogenetics46XX• FLT3-ITDNotDetected• Multiparameter FlowCytometryforMRDrevealedapopulationof
abnormalmyeloblasts (6%)
Case1
Consideringherpersistentdisease,whatisthenextbeststep?
A. AllogeneicHCT
B. 3rd inductionwithstandardchemotherapyregimen(FLAG,MEC,etc.)
C. ClinicalTrial
D. Enasidenib
E. Azacitadine/Venetoclax
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Case1
• ShewasenrolledonaClinicalTrialandwasabletoachieveaMorphologicalLeukemiaFreeStateafter3cyclesoftherapy• Multiparameter flowcytometryispositiveforMRDwith4.9%
abnormalblastsfound
• Intheinterim,herbrotherwasfoundtobea10/10HLAmatchdonor
• Hercoursehasotherwisebeenlargelyuncomplicated
Case1
WhatdoesthepresenceofMRDindicateinAML?
A. Higherrelapserate
B. IncreasedneedforHCT
C. WorseSurvival
D. Alloftheabove
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Case1
Whatistheroleofallogenictransplantatthistime?
A. Norole,awaitcountrecoveryandconfirmCR
B. ProceedwithmatchedrelateddonorallogeneicHCTnowwithoutcountrecovery
C. ProceedwithmatchedrelateddonorallogeneicHCTaftercountrecovery
D. Norole,continuewithClinicalTrial
E. Changechemotherapyregimens
Case1
• PatientunderwentmatchedrelateddonorallogeneicHCT
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Case1
Istherearoleforpost-transplantFLT3-directedtherapyasmaintenance?
A. Yes,restartMidostaurin
B. No
C. Yes,startSorafenib
D. Yes,ifonatrial
Case1KeyPoints
• ThestandardofcareforAMLisrapidlyevolving• FournewFDAapprovalsin2017• Midostaurin - FLT3inhibitor;(NEJM2017;377(5):454)
• Daunorubicin andCytarabine liposome(JCO34,no.15_supplMay2016)
• Gemtuzumab ozogamicin - anti-CD33antibody-drugconjugate(Leukemia2017;31(9):1855)
• Enasidenib - IDH2inhibitor(Blood2017;130(6):722)• Theneedforcytogeneticandmolecularanalysescanpresentachallenge
totheoptimizationoffront-linetherapyselection• ThereisanevolvingroleofMRDanalysisinthemanagementofAML
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Case2• 55yo manwithPMHincludingOA,RLS,OSAandAnxietywhopresents
withnewLhippainandAKIonlabscompletedbyPCP
• ExaminationisremarkableforpainwithROMoftheLhip;nootherconcerningfindingsnoted
• Pertinentlabsasfollows:Lab Value
Creatinine 3.67mg/dLCa 12.3mg/dLHgb 9.8g/dL
Albumin 3.9g/dLB2M 5.7mg/LLDH 120U/L
Lab ValueKappaLC 4800mg/dLLambdaLC 6mg/dLK/Lratio 800SPEP NoM-spikeIFE NegativeUIFE KappaLC
Case2
• BMBx iscompletedshowing30%monoclonalplasmacellpopulation• MMFISHshowedDel17p,Del13q,Del16q
• MRIPelvisrevealedafocal,1cmleftpelviclyticlesion
• Adiagnosisofsymptomaticmultiplemyelomaisconfirmed
• R-ISSIIIbasedonDel17pandB2M>5.5mg/L
• PatienthasanECOGof1andisonlylimitedbylefthippainandfatigue
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Case2
Whattherapyshouldberecommendedforthethispatient?
A. VRd +XRTtoLHiplesion
B. KRd +XRTtoLHiplesion
C. ClinicalTrial+XRTtoLHiplesion
D. Rd+XRTtoLHiplesion
E. Daratumumab/Vd +XRTtoLHiplesion
Case2
• PatientisstartedonVRd,whichhetolerateswell
• After4cycles,assessmentofdiseaserevealsaPR(>50%reductiononKappaLightChains)
• Heisthenassessedfortransplant
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Case2
ConsideringtheDel17p,whatistheroleoftransplantatthistime?
A. Norole,continuewithVRd andreassessresponse
B. Proceedtoauto-HCT
C. Proceedtoauto-HCTfollowedbyallo-HCT
D. Proceedtotandemauto-HCT
E. Norole,switchtreatmentregimenconsideringPR
Case2
• Patientthenproceedswithauto-HCTabout1monthaftercompletionofCycle4ofVRd• ToleratesHCT,complicatedonlybyneutropenicfever
• ReassessmentofdiseaseafterengraftmentandcountrecoveryshowsachievementofaCR
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Case2
Whattreatmentstrategyshouldbeconsiderednext?
A. MaintenanceLenalidomide
B. MaintenanceBortezomib
C. 2nd auto-HCT
D. Proceedtoallo-HCT
E. MaintenanceVRd
Case2
• PatientisstartedonmaintenanceLenalidomide andZolendronic Acid
• FrequentassessmentofdiseaseshowscontinuedCR
• Athisassessment1.5yearsaftertransplant,hisKappaLCisnotedtoberisingonceagainalongwithnewbonepain• Hehasnoothersignsofend-organdamage,butnewsymptomatic
lyticlesionsarefound
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Case2
Whattreatmentstrategyshouldbeinitiatedatthistime?
A. RestartVRd
B. 2nd auto-HCT
C. VTD-PACE
D. KRd
E. Daratumumab-basedregimen
Case2
• PatientisrestartedonVRd whichimproveshissymptoms,buthasnoeffectonhisKappaLC
• PatientthenisthestartedonVTD-PACEx3,whichhelpshimachieveaVGPR
• Hethenundergoesasecondauto-HCTfollowedbymaintenanceBortezomib
• ReassessmentofdiseasebyKappaLCandBMBx showsaCR
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Case2
• Sixmonthslater,patientisnotedtohaverisingKappaLConceagainalongwithnew,symptomaticlyticlesions(FDG-negative)andnoevidenceofend-organdamage
• PatientisstartedonKRd• Reassessmentofdiseaseafter7cyclesshowshehasachievedaCR
• Atthistime,heisanECOG1withagoodnutritionalstatusandnosignificantcomplicationsfromprevioustreatment/transplants
Case2
Whattreatmentoptionshouldbeofferednext?
A. Allo-HCT
B. ClinicalTrialwithCART-celltherapy
C. ContinueKRd untilprogression
D. Maintenancetherapy
E. TreatmentHoliday
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Case2
• Patientisofferedanallo-HCTashisbrotherisfoundtobea10/10HLAmatch
• HeisadmittedandgivenaFlu/Melprepfollowedbystemcellinfusion• HiscourseiscomplicatedbyG4GIGvHD requiringa5+month
admission
• Patientisnowtwoyearspost-transplantanddoingwellbarringsomechronicGvHD
Case2KeyPoints
• Inductionwithtripletnovelagenttherapyisthemainstayoffrontlinetreatmentforpatientswithmultiplemyeloma(Lancet2017;389(10068):519)
• Autologoushematopoieticcelltransplantfollowedbymaintenanceisrecommendedupfrontformosttransplant-eligiblepatientswitharesponsetoinduction• Standardrisk=Lenalidomide (JCO2017;35(29):3269)• Intermediate/Highrisk=Bortezomib (JCO2012;30(24):2946)
• Salvagenovelagenttherapy,secondauto-HCTandallo-HCTcanbeutilizedinthesettingofpreviouslytreatmentmultiplemyeloma
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Case3
• PatientunderwentLadrenalmassbiopsyshowingCD20+,CD10-,BCL6+,BCL2+,MUM1- DLBCLwithaKi67of80%;FISHdidnotrevealanytranslocationsbutMYCwasoverexpressedbyIHC
• BMBx completedandshowednoevidenceofdisease
• Patientalsofoundtohavealargepericardialeffusion,notFDG-avidonPET/CT;notamponadephysiologybyTTE;shethenunderwentpericardiocentesis withnoevidenceofdiseaseoncytology
Case3
WhatregimenshouldbeconsideredforMYC/BCL6overexpressionGCB-subtypeDLBCL?
A. R-CHOP
B. DA-R-EPOCH
C. R-Hyper-CVAD
D. R-CODOX-M/IVAC
E. R-CHOPfollowedbyAuto-HCT
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Case3
• WhatcharacteristicsofherdiseasewouldwarranttheadditionofITprophylaxis?
A. Diseaseonbothsidesofthediaphragm
B. MYC/BCL6overexpression
C. Retroperitonealinvolvementalone
D. LDHaboveupperlimitofnormalwith>1extranodal site
E. BandD
Case3
• PatientthenunderwentDA-R-EPOCHwithITMTX
• PET/CTcompletedafter3cyclesshowsasignificantresponsewithminimaldiseaseactivity
• Patientthencompleted6cyclesofDA-R-EPOCHwithITMTX
• PET/CTafter6cyclesshowedaCR
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Case3
ShouldupfrontAuto-HCTbeofferedforthispatient?
A. Yes,duetoextentofdisease
B. No,dueachievingCR
C. Yes,duetoMYCoverexpression
D. No,asthedataisunclear
E. Yes,asthedataisunclear
Case3• Auto-HCTwasdiscussedwiththepatientandshedecidedtoforgo
transplantatthistime
• ShethenstartedsurveillancewithH&Pevery3months
• Sixmonthsaftercompletingtreatment,thepatientpresentedtoanOSHEDwithseizures
• MRIBrainwascompletedshowingalargeLparietallesion;MRSpectroscopyandPerfusionwerealsocompleted,concerningforCNSrelapseofLymphoma
• LPwascompletedwithnegativecytologyandflow;Bx notcompleted
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Case3
Asfurtherimagingdidnotrevealanyothersitesofdisease,whatregimenshouldthepatientbeofferednext?
A. HDMTX+Ara-c
B. MTR
C. MATRix
D. MTR+WBRT
E. HDMTXalone
Case3• PatientwasstartedonMTR
• AfterC3,patientunderwentarepeatMRIshowinga50%decreaseinthesizeofthemass
• After6cycles,patientshowedacontinuedresponse
• Sheisoveralldoingwellandtoleratingtherapy;ECOG0
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Case3
• Whatistheroleoftransplantforthispatient?
A. Notransplantiswarranted
B. Allo-HCTshouldbeoffered
C. Noavailabledata
D. ConsolidativeBEAMorThiotepa-basedAuto-HCTshouldbeoffered
E. EAconsolidationshouldbeoffered
• IstherearoleforXRTforthispatient?
A. Yes,butonlyifsheisnotatransplantcandidate
B. NoroleforXRTatall
C. Yes,butonlyasapalliativeoption
D. Yes,namelytoimproveresponse
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Case3
• PatientwasofferedaconsolidativeAuto-HCTwithRituximab/Thiotepa/Busulfan/Cyclophosphamidepreparativeregimen
Case3KeyPoints
• PatientswithDouble-hitDLBCLareknowntohaveapoorprognosis;thisislessclearofDouble-expressor DLBCLbutthoughttobesimilar
• ResponsetoR-CHOPisknowntobepoor;dataforEPOCHispromisingwithCALGB/Alliance50303(subset)resultsstillpending
• ForCNSrelapse,regimenswithhigh-doseMTXorCytarabine arereasonablewithconsiderationofcombinations(MTR,MATRix)asotheroptionsextrapolatedfromPrimaryCNSLymphoma
• Duetopoorlong-termsurvival,high-dosechemotherapyfollowedbyauto-HCTshouldbeconsideredinyoung/fitpatients(J Clin Oncol.2015Nov;33(33):3903-10)