Association of Northern California Oncologists Hematologic ...Leukemias, Lymphomas, and Myeloma Chair: Joseph Tuscano, MD deLeuzeEndowed Professor of Medicine University of California,

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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)