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精选ppt1ElertE.Nature.2013;504:S2-S3.1796:Firstuseofimmunotherapy,Jennersmallpoxvaccine1976:BCGvaccineforbladdercancer1863:Connectionbetweenimmunothe

rapyandcancerrecognized1985:Interferonfirstapprovedforhairycellleukemia1992:IL-2approvedforRCC1997:FirstmAbforcancerapprov

ed,rituximab2008:FirstcancervaccineapprovedforRCC2010:Sipuleucel-Tapprovedforprostatecancer2011:CTLA-4inhibitorapprovedformelanom

a2014-2015:PD-1inhibitorsapprovedformelanoma,squamousNSCLC2015:Firstoncolyticvirusapprovedformelanoma2016:PD-1inhibitorap

provedforcHLPD-L1inhibitorapprovedforUC精选ppt2HL,Classictype,95%past40years,86%willlive5yearsafterdiagnosis.20%to30%relapseafterinitialtreat

mentorwillnotrespondtotherapyatall.Suchpatients:1.autologousstem-celltransplantation(ASCT).2.newertreatmentregimen+brentuximabvedotin,3.manypatientse

ventuallyworsens.精选ppt3Reed-Sternbergcellsfromgeneticchanges.WhichresultinanabundanceofimmunecheckpointmoleculesPD-L1andPD-L2.cHL,PD-L1a

ndPD-L2moleculeswerefoundin97%ofthe108specimenstestedresponseratestoPD-1inhibitorsarehigherinclassicHLthaninanyothertypeofcancerstudiedtoda

te.CBT，checkpointblockadetherapy，(免疫)检查点阻滞治疗精选ppt4病理类型影响PD-L1、2表达86%nodularsclerosis,11%mixed-cellularity3%nototherw

isespecified.病期影响基因扩增、预后Amplificationof9p24.1ismorecommoninpatientswithadvancedstagedisease（III/IV）andassociatedwithshorterP

FSinthisseries.精选ppt5chromosome9p24.1,resultinginoverexpressionofthePD-1ligandsPD-L1andPD-L2onthetumourcellsurface

.JAK2isalsolocatedonchromosome9p24.1,andalterationsinthisgeneincreaseJAK–STATsignalling,furtherinducingPD-L1

overexpression.精选ppt625%ofDLBCLtumorsexpressPD-1/PD-L1[Andorskyetal.2011]primarymediastinalB-celllymphoma(PMBL)which,similartoHL，frequent

lyharbors9p22amplificationleadingtooverexpressionofPD-L1/PD-L2[Shietal.2014].精选ppt7single-armphase2studyECOG0or1,nivolumabintravenouslyover60mina

t3mg/kgevery2weeksuntilprogressionAug26,2014～Feb20,2015,34hospitalsandacademiccentresacrossEuropeandNorthAmerica.primaryendp

ointwasobjectiveresponse,medianfollow-upof8·9months.精选ppt8lymphomawentintoremissionin53(66%)of80patientsanddisappearede

ntirelyinseven.NearlyallpatientswithclassicHLwhorespondedtothetreatmenthadatleasta50%reduction,andresponseslasted

8months.Nivolumabwasgenerallywelltolerated.Themostcommonadverseeffectsofanygradewerefatigue,infusion-relatedreaction,andrash.精选pp

t9Severeadverseeffects,suchaslowbloodcounts(neutropenia)andliverenzymeabnormalities(increasedlipase),occurredinonly5%ofpatients.Nivolum

ab，cHLrelapsingorprogressingafterautologousHSCTandpost-transplantationbrentuximabvedotin，FDA，May2016[USFoodandDrugAdmi

nistration:Nivolumab(Opdivo)forHodgkinlymphoma.http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDr

ugs/ucm501412.htm].精选ppt10Multicenter,multicohortphaseIbtrial,open-label,December2013toSeptember2014.

Primaryendpoints:safety,CRSecondaryendpoints:OR,DoR,PFS,OS,biomarkersResponsetotreatmentwasassessedatweek12andevery8week

sthereafter.cHLptswithECOGPS0/1,previousbrentuximabvedotinfailure,ASCTfailureorineligibility(N=31)Discontinuationpermitted≥24wksPembrol

izumab10mg/kgIVQ2WCRPRorSDPDTxto24mosorPDorintolerabletoxicityDiscontinuationArmandP,etal.ASH2015.Abstract584；A

rmandP,etal.JCO,34:3733-3739,2016.精选ppt11CharacteristicPembrolizumab(N=31)Medianage,yrs(range)32(20-67)Pathology,n(%)•Nodularscl

erosis•Mixedcellularity30(97)1(3)Previousradiationtherapy,n(%)10(32)Previoussystemictherapy,n(%)•2-4•≥514(45)17(55)Previou

sbrentuximabvedotinfailure,n(%)31(100)ASCT,n(%)•Failure•Ineligibility/refusal22(71)9(29)ArmandP,etal.ASH2015.Abst

ract584；ArmandP,etal.JCO,34:3733-3739,2016.精选ppt1290%ofptshaddecreasesintargetlesionburdenincreasescirculatingnumbersofTandNKcells,up

regulatesTCR/IFN-γsignalingOf20ptswithCR/PR:Stillontreatment:n=7DiscontinuedtreatmentCR:n=1PRswitchedtx:n=1

AE:n=1AllogeneicSCT:n=3PD:n=7Endpoint,%Total(N=31)TransplantFailure(n=22)TransplantIneligibility/Refusal(n=9)ORR

•CR•PR651648731459442222SD231833PD13922DoR≥24wks•Responsesoccurringby12wks7180PFSat24wks69ArmandP,etal.ASH2015.Abstract584.；Ar

mandP,etal.JCO,34:3733-3739,2016精选ppt13theORRtocheckpointblockadeinNHLisgenerallylowercomparedwithHLandPMBL.phaseItrialofipilimumabin18patie

ntswithR/RNHL,anORRof11%wasobserved[Anselletal.2009].Notably,responses,althoughlow,werequitedurablewithanongoingCRlastingmorethan31and1

9monthsinoneDLBCLandoneFLpatient,respectively.精选ppt14phaseI,nivolumabinvarioussubtypesofNHL(n=54)revealedthehigh

estrateofORRwasachievedinpatientswithFLat40%,closelyfollowedbyDLBCLat36%[Lesokhinetal.2016].Patientswit

hT-celllymphomas(n=23)werealsoincluded,butdidnotfareaswellwithvariableresponses:15%ORR(allPR)inmycosisfungoidesa

nd40%inperipheralT-celllymphoma.SimilarstudieswithpembrolizumabinpatientswithNHLarecurrentlyongoing.精选ppt151.single-armstudy2.lo

ng-termfollow-upwillberequiredtodeterminethedurabilityofresponses3.ongoinghostimmunereactionswithintumoursmighthavecontributedtopersi

stent¹⁸F-FDGuptake精选ppt161.PD-L1、2表达程度是否影响疗效？2.治疗持续多长时间最合适？3.获得CR后的终止治疗，何时开始？4.CR不是很高，治愈的可能性？5.PR的意义有多

大？6.比起其他的治疗，如放疗±其他治疗，孰优？性价比？精选ppt17forrelapsedaswellasnewlydiagnosedclassicHLisunderway.KEYNOTE-204phaseIIItrial，comparep

embrolizumabvsBVinptswithR/RcHL(NCT02684292)nivolumabwithbrentuximabvedotinandipilimumab(ClinicalTrials.govidentifiers:

NCT02758717,NCT01896999,andNCT02304458).otherhematologicmalignancies,aswellasinmultiplemyeloma(ClinicalTrial.govi

dentifier:NCT01953692).精选ppt18谢谢聆听!精选ppt19