GPS在弥漫大B细胞淋巴瘤中的应用.ppt

弥漫大B细胞淋巴瘤整体治疗策略,上海交通大学医学院附属瑞金医院血液科李军民,主要内容,诱导治疗一线治疗目的:以治愈为目标标准治疗vs精准治疗:预后分层治疗巩固强化治疗造血干移植（自体）的地位CLL及FL治疗进展靶向治疗进展,流行病学与形态学,弥漫大B细胞淋巴瘤(DLBCL)是非霍奇金淋巴瘤(NHL)中最常见类型,主要内容,诱导治疗一线治疗目的:以治愈为目标标准治疗vs精准治疗:预后分层治疗巩固强化治疗造血干移植（自体）的地位复发/难治的解救治疗二线方案的选择及造血干细胞移植的作用靶向治疗进展,CHOP时代治愈率：35-40%,FisherRI,NEnglJMed1993;328:10021006,利妥昔单抗时代治愈率：50-60%,时间(年),生存率,p1subject,*IncludesonecaseeachofCMVreactivation,disseminatedZoster,andthrush,Percentage(%),Response,Response,SummaryandConclusions,LenalidomideaddedtoBRresultsinhighefficacyinpreviouslyuntreatedCLLNotabletoxicitieswererash,neutropeniadespitepegfilgrastimsupport,andpulmonaryembolismdespiteaspirin.NoDLTswereobservedatthetargetdoselevelof10mglenalidomide,butdosereductionsinlatercycleswerecommonduetoaccruingtoxicity.,LBR,LBR,LBR,LBR,LBR,LBR,L,L,L,L,L,L,L,15913172125293337414549,Weeks,CT,CT,PETMRD,CT,PETMRD,Lenalidomide-Rituximab-Bendamustineinfirstlineforpatients65withmantlecelllymphoma:FinalresultsoftheNordicLymphomaGroupMCL4,Rituximab:375mg/m2day1Bendamustine:90mg/m2day1-2Lenalidomide:atMTD.Initiallyd1-21,afteramendmentd1-14,Response:CT/BMMRDBM/PBPET(6m+12m),Lenalidomide:atMTDd1-21,Response,Conclusions,LBRisaveryactiveregimenindifferentlymphoprolipherativediseasesThecombinationisverytoxicifthedrugsaregiveatfulldoseAsafescheduleseemstobe:Bendamustine70mg/m2d1+2Rituximab375mg/m2d1Lenalidomide10mg/dd1-14q28dThisregimen,althoughactive,needstobecomparedtostandardregimensinrandomisedtrials,FLremainsanincurabledisease,Evenwhenthemostpotenttreatmentisapplied,Ladetto,M.etal.Blood2008,FLremainsanincurabledisease,IndependentreviewofCTresponsesinthetrialSAKK35/10comparingrituximabwithrituximabpluslenalidomideinuntreatedfollicularlymphomapatientsinneedoftherapy,EmanueleZucca,AnnaVanazzi,BjornOstenstad,UlrichJMMey,DanielRauch,BjrnEWahlin,FelicitasHitz,MicaelaHernberg,Ann-SofieJohansson,PeterdeNullyBrown,HansHagberg,AndrsJMFerreri,AndreasLohri,UrbanNovak,ThiloZander,HanneBersvendsen,MarioBargetzi,WalterMingrone,FatimeKrasniqi,StephanDirnhofer,HanneHawle,SimonaBerardi,SteffiDemmel,StephanieRondeau,andEvaKimby,Zuccaetal.HematolOncol(13-ICMLAbstracts).2015;33:105-6abs.011,SAKK-NLG35/10:RvsR-LenSensitivityAnalysis(Responseatwk23),InvestigatorAssessmentORR,82%vs61%,IRRconsideredonlythetargetlesionsmeasurableonCTscans12pts(10receivingR+L)hadbonemarrowinvolvedatbaselineandnotre-assessedatweek234pts(3receivingR+L)hadbonemarrowinvolvedatbaselineandstillinvolvedatweek23,IRRAssessmentORR,78%vs57%,Zuccaetal.HematolOncol(13-ICMLAbstracts).2015;33:105-6abs.011,Chemo-freetriplet:PhaseI,Abstr.106Ublituximabnewanti-CD20(otherepitope)TGR-1202=newPi3Kd(DELTA)inhibitorIbrutinibWelltolerated:ORR86%inR/Rpts,主要内容,诱导治疗一线治疗目的:以治愈为目标标准治疗vs精准治疗:预后分层治疗巩固强化治疗造血干移植（自体）的地位复发/难治的解救治疗二线方案的选择及造血干细胞移植的作用靶向治疗进展,Newoptionsin2015:“targetedtherapy”and“immunotherapy”,PD-1Blockade,Anti-CD30antibodydrugconjugateBrentuximabVedotin,Nivolumab,50,B-NHL中重要的细胞通路：BCR信号通路,BCR信号通路的靶向药物,Bruton酪氨酸激酶(BTK),Bruton酪氨酸激酶抑制剂：Iburtinb,LancetOncol2014;15:101926,免疫调节药物Lenalidomide,Lenalidomide是新一代的抗癌免疫调节剂（IMiD），可通过改变细胞因子的生成来影响免疫系统，达到提升免疫反应、增加免疫细胞活性及抑制炎症反应的效果亦可抑制VEGF来抑制肿瘤细胞血管生成，直接抑制肿瘤细胞的增生其不良反应较Thalidomide少，具有广阔的应用前景。,Lenalidomide联合R-CHOPREAL07研究结果,LancetOncol.2014Jun;15(7):730-7,Lenalidomide联合R-CHOPREAL07研究结果,LancetOncol.2014Jun;15(7):730-7,Participantsweretoreceive15mgorallenalidomideondays114ofsix21-daycyc