彌漫大B細胞淋巴瘤進展課件

NewsAboutDLBCLin2013ASHDr.JunminLITheValidityofIPIinRituximabEraIPIInSelectingPatientsWithDiffuseLargeBCellLymphomainRituximabEraHavinginmindthatIPIisbasedon5clinicalcharacteristicsanditisconstructedinthepre-rituximabisclearthatR-IPIshouldbetestedinrituximaberatoprovideanyinformationofitsvalidity.Thestudyretrospectivelyanalyzedunselectedpopulationof80DLBCLpatients.Onewith0to2factorsaspatientswithlowrisk.Patientswithmorethan3factorsareconsideredashighrisk.Thereisstatisticallysignificantdifferenceinoverallsurvivalbetweentwogroupswithfive–yearsoverallsurvival70%forlowriskpatientsand47%forhighrisk.TheValidityofIPIinRituximabEraIPIInSelectingPatientsWithDiffuseLargeBCellLymphomainRituximabEraHigh-riskpatientsmaybecandidatesforautologoustransplantationasinitialtreatment,havinginmindthatintherituximaberarelapsesoccurveryearlyinthefirstyearandaredifficulttobetreated.R-IPIscoreissignificantpredictorandshouldbeusedforriskstratificationofpatientswithaggressiveB-celllymphoma.NewPrognosticFactorinDLBCL

in2013ASHDiffuseLargeBCellLymphoma:RoleOfMYC,BCL2,BCL6ProteinExpressionsandTranslocationsDatafrom65patientsdiagnosedbetweenJune2001andFebruary2012wereavailableforanalysis.PositiveMYCproteinexpressionortranslocationwasfoundin16(24%)patients.7patientshadDHLwith5patientshavingMYC/BCL2translocations,1patient-MYC/BCL6and1patientwithMYC/BCL2/BCL6(Triplehit)translocations.9patientshadMYCproteinexpressionwithorwithouttranslocationwithco-expressionofeitherBCL2orBCL6protein.81%(53/65)ofpatientshadBCL2expression(14hadtranslocation),65%(42/65)hadBCL6expression(7hadtranslocation),and24%(16/65)hadMYCproteinexpression(12hadtranslocation).NewPrognosticFactorinDLBCL

in2013ASHDiffuseLargeBCellLymphoma:RoleOfMYC,BCL2,BCL6ProteinExpressionsandTranslocations25patients(38%)hadasingleproteinexpression;ofwhich14patientshadBCL2,10patientshadBCL6and1patienthadMYC.24patients(37%)werepositiveforbothBCL2andBCL6co-expression;ofwhich5patientshadpositivetranslocationsbyFISH.61%(40/65)ofthepatientsdidnothaveFISHstudiesfollowingimmunohistochemistry.NewPrognosticFactorinDLBCL

in2013ASHDiffuseLargeBCellLymphoma:RoleOfMYC,BCL2,BCL6ProteinExpressionsandTranslocations59%ofthepatientsachievedacompleteremission(CR),22%hadabestresponseofpartialremission(PR),and17%didnotrespondtotreatment.Aswithresponsetochemotherapy,patientswithasingleproteinexpressionwitheitherBCL2orBCL6,orco-expressionwithbothBCL2/BCL6hadsimilaroutcomesintermsofoverallsurvival(79.9vs70.6months)andCR(70%vs.79%).Whereas,patientswithproteinexpression/translocationinvolvingMYCtendedtohavepooreroutcomes:19%(3/16)hadCR(p=.0005)andestimatedmediansurvivalof11.5months(p=.005).NewPrognosticFactorinDLBCL

in2013ASHDiffuseLargeBCellLymphoma:RoleOfMYC,BCL2,BCL6ProteinExpressionsandTranslocationsConclusion:DiffuselargeBcelllymphomasinvolvingco-expressionofMYCproteinwithBCL2orBCL6haveasignificantlylowersurvivalratecomparedtothepatientswithsingleproteinexpressionofBCL2orBCL6aswellasco-expressionofBCL2andBCL6.Inadditiontoobtainingcytogeneticstudies,weemphasizetheneedtoconductprospectiveclinicaltrialswhichcanaimattheoptimaltreatmentstrategiesforthissubsetofDLBCLpatientsexpressingtheMYCproto-oncogenewithBCL2and/orBCL6proteins.NewPrognosticFactorinDLBCL

in2013ASHConcurrentExpressionOfMYC/BCL2ProteinInNewlyDiagnosedDLBCLIsNotAssociatedWithAnInferiorSurvivalFollowingEPOCH-RTherapyImmunohistochemistryforMYCandBCL2inpatientswithnewlydiagnosedDLBCLwhoreceivedDA-EPOCH-Rorshort-course(SC)-EPOCH-RRIHC.IHCwaspositiveforMYCin28/48(58%)casesandpositiveforBCL2in24/51(47%).36/51(71%)and15/51(29%)ofcaseswereofGCBandnon-GCBoriginrespectively.Theycomparedsurvivalinthe4groups:MYC+/BCL2+,MYC+/BCL2-,MYC-/BCL2+andMYC-/BCL2-.PFSandOSwerenotsignificantlyinferiorinanygroup(globalpvalue=0.5(PFS)and0.8(OS)).NewPrognosticFactorinDLBCL

in2013ASHConcurrentExpressionOfMYC/BCL2ProteinInNewlyDiagnosedDLBCLIsNotAssociatedWithAnInferiorSurvivalFollowingEPOCH-RTherapyConclusions:InDLBCLpatientstreatedwithDA-EPOCH-RandSC-EPOCH-RR,concurrentexpressionofMYCandBCL2proteindidnotcorrespondwithaworseclinicaloutcome.However,celloforigin(GCBversusnon-GCB)waspredictiveofoutcome.MYC+/BCL2+casessegregatewiththenon-GCBsubtype.NewPrognosticFactorinDLBCL

in2013ASHTheRoleOfModifiedGlasgowPrognosticScoreAsPredictorInDiffuseLargeBCellLymphomaTreatedWithTheR-CHOPRegimenThestudyfoundthathighmGPSwereassociatedwithpoorprognosticfactorsincludingolderage(>60years),extranodal(EN)involvement,advanceddiseasestage,unfavorableIPIscores,andthepresenceofBsymptoms.TheCRrateafter3cyclesofR-CHOPchemotherapywassignificantlyhigherinpatientswithmGPSof0(53.8%)comparedtothosewithmGPSof1(33.3%)or2(25.0%)(P=0.001).PatientswithmGPSof0hadsignificantlybetterOSthanthosewithscoresof1(5-yearPFS,vs.74.1%)or2(80.9%vs.54.7;

P=0.036).NewPrognosticFactorinDLBCL

in2013ASHTheRoleOfModifiedGlasgowPrognosticScoreAsPredictorInDiffuseLargeBCellLymphomaTreatedWithTheR-CHOPRegimenPatientswithmGPSof0alsodisplayedsignificantlybetterOSthanpatientswithmGPSof2(P<0.001).Conclusion:Similartoseveralothercancers,GPScanbeanindependentpredictorofsurvivaloutcomesinDLBCLpatientstreatedwithR-CHOPtherapy.NewPrognosticFactorinDLBCL

in2013ASHPrognosticImplicationOfCirculatingVascularEndothelialGrowthFactorInPatientsWithDiffuseLargeB-CellLymphomaVascularendothelialgrowthfactor(VEGF)playsanimportantroleinangiogenesisandprogressionofcancer,andbloodlevelofVEGFhasbeenknowntopredictofoutcomeinseveraltypesofcancer.Thestudyinvolved127DLBCLpatientstreatedbyR-CHOP.TheyinvestigatedthecorrelationbetweenclinicalparametersandbloodVEGFlevels.NewPrognosticFactorinDLBCL

in2013ASHPrognosticImplicationOfCirculatingVascularEndothelialGrowthFactorInPatientsWithDiffuseLargeB-CellLymphomaBothserumandplasmaVEGFshowedthesignificant(p<0.01)correlationwithserumLDHlevel,AnnArborstageandmultipleextranodalinvolvement,butnotwithage,gendernorperformance.IPIshowedstrongpredictionforprognosisinourdataset(HR3.80,95%CI1.64-8.81,p=0.02),andtheVEGFlevelsofhigh/high-intermediateIPIgroupweresignificantlyhigherthanthoseoflow/low-intermediategroup[serumVEGF1088(±838.0)and557(±377.2),p<0.001andplasmaVEGF79(±131.6)and176(±212.2),p=0.002].NewPrognosticFactorinDLBCL

in2013ASHPrognosticImplicationOfCirculatingVascularEndothelialGrowthFactorInPatientsWithDiffuseLargeB-CellLymphomaWiththemedianfollow-upof44months,highserumVEGFlevels(higherthanthemedian)weresignificantlyassociatedwithshortsurvival(HR2.74,95%CI1.13-6.60,p=0.025),thoughtheplasmaVEGFlevelsdidnotshowtheassociationsimilartotheserumsamples(HR1.40,95%CI0.63-3.12,p=0.414).ThepatientswithhigherserumVEGFthanthemedianvalueshowedsignificantlylowersurvivalratecomparedtothelowgroup(3-yearsurvivalrates,68.6%vs.85.6%,p=0.019).NewPrognosticFactorinDLBCL

in2013ASH25-OH-Vitamin-DDeficiencyImpairsRituximab-MediatedCellularCytotoxicityandIsAssociatedWithAnInferiorOutcomeOfElderlyDLBCLPatientsTreatedWithRituximabPretreatment25-OH-vitamin-Dserumlevelsfrom359patientstreatedintheprospectivemulticenterRICOVER-60trialwith6or8cyclesofCHOP-14withandwithout8cyclesrituximaband63patientsintheRICOVER-noRTstudytreatedwith6xCHOP-14+8xRweredetermined.NewPrognosticFactorinDLBCL

in2013ASH25-OH-Vitamin-DDeficiencyImpairsRituximab-MediatedCellularCytotoxicityandIsAssociatedWithAnInferiorOutcomeOfElderlyDLBCLPatientsTreatedWithRituximabRICOVER-60patientswithVDD(definedasserumlevels≤8ng/ml)andtreatedwithrituximabhada3-yearevent-freesurvivalof59%comparedto79%inpatientswith>8ng/ml.3-yearoverallsurvivalwas70%and82%,respectively.Inpatientstreatedwithoutrituximab3-yearEFSwasnotsignificantlydifferentinpatientswithvitamin-Dlevels≤8and>8ng/ml(HR1.2;p=0.388).Rituximab-mediatedcellulartoxicity(RMCC)againsttheCD20+

celllineDaudiasdeterminedbyLDHreleaseassayincreasedsignificantly(p<0.005)in5/5vitamin-D-deficientindividualsaftervitamin-Dsubstitutionandnormalizationoftheirvitamin-Dlevels.NewPrognosticFactorinDLBCL

in2013ASHPrognosticSignificanceOfSystemicInflammatoryFactorsInPatientsWithDiffuseLargeBCellLymphomaTreatedByR-CHOPSystemicinflammatoryfactorssuchasC-reactiveprotein(CRP),β2-microglobulin(B2MG),andferritinweredocumentedanprognosticfactorinpatientswithhematologicmalignanciesincludinglymphoma.Atotalof188patientswhonewlydiagnosedDLBCLandreceivedanrituximabcombinedchemotherapy.PretreatmentserumCRP,B2MG,andferritinweremeasuredwithin4weeksbeforethebeginningoffirstlinechemotherapy.NewPrognosticFactorinDLBCL

in2013ASHPrognosticSignificanceOfSystemicInflammatoryFactorsInPatientsWithDiffuseLargeBCellLymphomaTreatedByR-CHOPSystemicinflammatoryfactorsscoreweregiven1pointifserumlevelsweremorethannormalrange(CRP;0.8mg/dL,B2MG;2.5mg/Landferritin;220ng/ml).Systemicinflammatoryriskweredividedintothreegroupsaccordingtosystemicinflammatoryfactorsscores;lowriskwas0score,intermediateriskwas1or2score,andhighriskwas3scorerespectively.5-yearprogressionfreesurvivalrates(PFS)were66.9%,65.0%and10.6%inriskgroupsrespectively(p<0.001).5-yearoverallsurvivalrates(OS)were74.4%,48.8%and19.8%inriskgroupsrespectively(p<0.001).NewPrognosticFactorinDLBCL

in2013ASHPrognosticSignificanceOfSystemicInflammatoryFactorsInPatientsWithDLBCLTreatedByR-CHOP5yearsoverallsurvivalcurvesaccordingtoSystemicinflammatoryfactorscoreinpatientswithDLBCL.NewPrognosticFactorinDLBCL

in2013ASHPrognosticSignificanceOfSystemicInflammatoryFactorsInPatientsWithDiffuseLargeBCellLymphomaTreatedByR-CHOPConclusions:

Systemicinflammatoryfactor(CRP,B2MGandferritin)scorewereassociatedwithsurvivaloutcomesinpatientswithDLBCLtreatedbyR-CHOP.However,furtherstudiesareneededtoconfirmprognosticvalueofsystemicfactorssuchasCRP,B2MGandferritin.NewPrognosticFactorinDLBCL

in2013ASHImpactOfBoneMarrowInvolvementOnOutcomeOfYoungPatientsWithHigh-RiskDLBCLTreatedWithRituximabDose-DenseChemotherapyFollowedByIntensifiedHDC+ASCTOrStandardRituximabDoseDenseChemotherapyTheroleofbonemarrow(BM)involvementasprognosticfactorinuntreatedyoungpatientswithdiffuselargeB-celllymphomaatpoorprognosisisstillamatterofdebate.RecentdatashowedanadverseprognosticroleofBMinvolvementinDLBCLincludingpatientsbothatlowandhighIPIscore.NewPrognosticFactorinDLBCL

in2013ASHConclusions:BonemarrowinvolvementisastrongadversepredictorofoutcomeinyoungpatientswithuntreatedDLBCLatpoorprognosistreatedwithR-chemotherapyregardlessofintensificationwithHDC+ASCT.PFSbyBMinvolvementNewApproachforElderlyDLBCL

in2013ASHDoseOfVincristinedidn’tPredictOutcomeOfTreatmentForElderlyDLBCLPatientsMorethan40%ofpatientswithDLBCLareolderthan70yearsoldatdiagnosis,andageisknownasapoorprognosticfactor.Therefore,itisimportanttooptimizetreatmentstrategyandchemotherapyfortheelderlywithDLBCLtoimprovetheiroutcome.Weexperiencednew93patientsagedover70years(41.9%ofallDLBCLcases).Medianobservationperiodofwas52.7months.R-CHOPandR-CHOP-likeregimeswereadministratedinto78and4patientsrespectively.NewApproachforElderlyDLBCL

in2013ASHDoseOfVincristinedidn’tPredictOutcomeOfTreatmentForElderlyDLBCLPatientsThemediandosesofADR,CPM,andVCRwere69.51±15.2%,70.23±20.0%and59.1±28.1%oforiginalregimen,respectively.%ofVCRtooriginalCHOPregimenwassignificantdifferentbetweenage70-79andagemorethan80(p<0.0001),butOSby%ofactualdoseVCRtooriginalCHOPwasnotdifferent(50%<vs.≧50%,p=0.62),suggestingthatdoseofVCRdidn’tpredictoutcomeoftreatment.ItmightsuggestthatdoseofVCRcouldbereducedwithkeepingtreatmentoutcometoimproveQOLofsurvivorswhosufferfromperipheralneuropathy.NewApproachforElderlyDLBCL

in2013ASHWeeklyFourTimesRituximabConsolidationFollowingReducedCyclesOfR-CHOPInductionChemotherapyInExtremelyElderlyPatientsWithDiffuseLargeBCellLymphomaPooroutcomeofpatientswithelderlydiffuselargeB-celllymphoma(DLBCL)hasbeenlinkedtotheirdecreasedabilitytoreceivefullcourseofR-CHOP,dose-reductionofchemotherapyduetotoxicitiesandtheirconcomitantdiseasetointerruptthetreatment.Thestudyisaimedtodetermineobjectiveresponse,toxicitiyandclinicaloutcomeofweeklyfourtimesrituximabaugmentationafterreducedcyclesofR-CHOPinextremelyelderlypatientswithDLBCL.NewApproachforElderlyDLBCL

in2013ASHWeeklyFourTimesRituximabConsolidationFollowingReducedCyclesOfR-CHOPInductionChemotherapyInExtremelyElderlyPatientsWithDiffuseLargeBCellLymphomaR-CHOPwasinfusedevery21days,withinitialdose-intensityofCHOPregimenwasmodulatedaccordingtoCharlsonComorbidityIndex(CCI).IfpatientswerewithCCI<1,patientsweretreatedwithstandarddoseofCHOP,however,ifpatientswithCCI≥1,patientswerewith75%ofconventionaldoseinitially.Rituximabconsolidation(375mg/m2)wastreatedweeklyfourtimes,atthetimeoffullrecoveryafter4th

R-CHOP.Trimethoprim/sulfamethoxasole(160mg/800mg,1Torally)wasgivendailyduringrituximabconsolidation.NewApproachforElderlyDLBCL

in2013ASHWeeklyFourTimesRituximabConsolidationFollowingReducedCyclesOfR-CHOPInductionChemotherapyInExtremelyElderlyPatientsWithDiffuseLargeBCellLymphoma51DLBCLpatientswereenrolled.36outof51patientscouldbeproceededtowardweeklyfourtimesrituximabconsolidation.35patients(68.6%)presentedwithhigh-intermediateorhighriskbasedonIPIand12patients(23.5%)wereclassifiedwithascoreof2byGlasgowprognosticscore(GPS).31patients(60.8%)werestartedwithdecreaseddoseofCHOPwithmedian75%reductionofCHOP.2-yearprobabilityofprogression-freesurvival(PFS)was71.5±7.9%with10relapses.TheadverseeventsweremainlyrelatedwithhematologictoxicitiesandneutropenicinfectionsduringR-CHOP.However,notoxicitieswerereportedassociatedwithrituximabweeklyinfusionandnoadverseeventsrelatedwithdelayedinfectionafterrituximabconsolidation.NewApproachforElderlyDLBCL

in2013ASHWeeklyFourTimesRituximabConsolidationFollowingReducedCyclesOfR-CHOPInductionChemotherapyInExtremelyElderlyPatientsWithDiffuseLargeBCellLymphomaConclusions：RituximabconsolidationafterreducedcyclesofR-CHOPresultedinafavorableresponsewithhightolerabilityandcouldbeagoodcompromisebetweenefficacyandtolerabilityforextremelyelderlyDLBCL.NewApproachforElderlyDLBCL

in2013ASHInterimResultsFromaPhaseIIStudyOfOxaliplatin-GemcitabinePlusRituximab(R-GemOx)AsFirst-LineTreatmentInElderlyPatientsWithDiffuseLargeB-CellLymphomaAnthracycline-containingregimensarestillthecornerstoneofelderlypatientswithdiffuselargeB-celllymphoma(DLBCL),althoughthetherapeuticresponseisacceptable,highincidenceofco-morbiditiesandtreatment-relatedadverseeffect.Aplatinum-basedregimen(oxaliplatin-gemcitabine)whichiswidelyusedtotreatsolidtumorsplusanti-CD20antibodyrituximab(R-GemOx)asfirst-linetreatmentinelderlypatientswithDLBCL.NewApproachforElderlyDLBCL

in2013ASHInterimResultsFromaPhaseIIStudyOfOxaliplatin-GemcitabinePlusRituximab(R-GemOx)AsFirst-LineTreatmentInElderlyPatientsWithDiffuseLargeB-CellLymphomaEligiblepatientsincludedthosewithpreviouslyuntreated,CD20positiveDLBCL,≥70yearsofageor≥60yearswithECOGperformancestatusscore≥2.TherapeuticprotocolofR-GemOxregimenwasasfollows:rituximab375mg/m2

i.v.onday1;gemcitabine1g/m2

i.v.onday2;oxaliplatin100mg/m2

i.v.onday2,eachcycleoftreatmentwasadministeredevery14to21daysaccordingtorecoveryoftoxicities.NewApproachforElderlyDLBCL

in2013ASHInterimResultsFromaPhaseIIStudyOfOxaliplatin-GemcitabinePlusRituximab(R-GemOx)AsFirst-LineTreatmentInElderlyPatientsWithDiffuseLargeB-CellLymphomaTheoverallresponserate(ORR)amongtreatedptswas81.8%,with63.6%ofpatientsachievingCR/CRuand18.2%achievingPR,onepatient(4.5%)hadSDand3patients(13.3%)hadPD.Withthemedianfollow-upof15months(4-34),progression-freesurvivalratewas50.6%,andoverallsurvivalratewas67.2%.5yearsPFSandOSaccordingtoSystemicinflammatoryfactorscoreinpatientswithDLBCLNewApproachforElderlyDLBCL

in2013ASHInterimResultsFromaPhaseIIStudyOfOxaliplatin-GemcitabinePlusRituximab(R-GemOx)AsFirst-LineTreatmentInElderlyPatientsWithDiffuseLargeB-CellLymphomaIntermsoftoxicities,mosttreatment-relatedadverseevents(AEs)weremildormoderateinseverity.Themostcommongrade≥3AEsweregastrointestinalcomplicationsincludingdiarrheaandvomiting(18.2%)andbonemarrowsuppression(13.6%),othernonseriousAEsobservedincludedhypodynamia,mildparesthesiaandhepaticinjury.Noclinicalimpairmentofcardiacandnephrotoxicitywereobserved.Conclusions:R-GemOximmunochemotherapyregimenishighlyactiveandwell-toleratedinpreviouslyuntreatedelderlypatientswithDLBCL.TheencouraginginterimdatasuggestR-GemOxisapromisingfirst-lineregimenforthissubgroupofpatients.NewApproachforR/RDLBCL

in2013ASHLenalidomideInCombinationWithR-ESHAP(LR-ESHAP)InPatientsWithRelapsedOrRefractoryDiffuseLargeB-CellLymphomaCandidatesToAutologousStem-CellTransplantationDiffuselargeB-celllymphoma(DLBCL)patientswithrelapsedorrefractorydiseaseafterrituximab-containingfirst-linetherapyhaveapooroutcomewiththecurrentsalvageregimens.ThestudyconductedaphaseIbtrial(3+3design)toestablishthesafety,tolerabilityanddeterminationofthemaximum-tolerateddose(MTD)oflenalidomideincombinationwithR-ESHAP(LR-ESHAP)inpatientswithrelapsedorrefractoryDLBCL.NewApproachforR/RDLBCL

in2013ASHLenalidomideInCombinationWithR-ESHAP(LR-ESHAP)InPatientsWithRelapsedOrRefractoryDiffuseLargeB-CellLymphomaCandidatesToAutologousStem-CellTransplantationSubjectsreceivedthreecyclesoflenalidomide(5,10or15mg)givenondays1to14ofevery21-daycycle,incombinationwithR-ESHAPsalvagechemotherapyatstandarddoses(rituximab375mg/m2

day1,etoposide40mg/m2

days1-4,cisplatine25mg/m2

days1-4;citarabine2000mg/m2

day5,andmethilprednisolone500mgdays1-5).RespondingpatientsreceivedBEAMfollowedbyASCT.Todate,16/20seriousadverseevents(SAEs)havebeenreported,including5episodesoffebrileneutropenia,2pneumonia,2sepsis,1ionicimbalance,1renaltoxicity,1facialangioedema,2thrombosis,and1hepatictoxicity,allofthemrecovered,andtherewerenotreatment-relateddeaths.NewApproachforR/RDLBCL

in2013ASHLenalidomideInCombinationWithR-ESHAP(LR-ESHAP)InPatientsWithRelapsedOrRefractoryDiffuseLargeB-CellLymphomaCandidatesToAutologousStem-CellTransplantationOfthe18patientswithatleastonepost-baselinetumorassessment,theoverallresponseratetoLR-ESHAPwas77.8%(44.4%completeremission).All18patientsweresuccessfullymobilizedafterone(13patients)ortwo(5patients)mobilizationprocedures,and14(70%oftheoverallseries)underwentASCTaccordingtoprotocol.Withamedianfollow-upof7.4(2.9to27.6)months,theestimated1-yearprogression-freesurvivalandoverallsurvivalwere52%and72%,respectively.Conclusions:LR-ESHAPshowsanacceptablesafetyproencouragingactivityinrituximab-pretreatedrelapsedorrefractoryDLBCLpatients.NewApproachforR/RDLBCL

in2013ASHIncorporatingHigh-DoseIVMethotrexateIntoInitialTherapyResultsInLowerRatesOfCentralNervousSystem(CNS)RelapseInPatientsWithHigh-Risk(DLBCL)CNSrelapseinDLBCLisadevastatingcomplicationandtheoptimumstrategyforpreventionremainsunclear.Thestudycompared3prophylaxisstrategies:priorto2003intrathecal(IT)methotrexate(MTX)inconjunctionwithCHOPchemotherapy“group1”wasthemainstrategy;from2003onwards,R-CHOP(mostly)withITMTXwasfollowedbytwocyclesofhighdoseintravenous(IV)MTX(1-3g/m2)“group2”;patients<65yearsofagewithageadjustedIPIof≥2weretreatedwithdoseintensivetherapycontaininghigh-doseanti-metabolites(Hyper-CVADorCODOXM-IVAC,withrituximabafteritbecameavailable)whichincludedbothITandIVMTX“group3”.NewApproachforR/RDLBCL

in2013ASHIncorporatingHigh-DoseIVMethotrexateIntoInitialTherapyResultsInLowerRatesOfCentralNervousSystem(CNS)RelapseInPatientsWithHigh-Risk(DLBCL)Overall,208ptswereidentified,with32,134and42ingroups1,2and3respectively.Withamedianfollowupof3.7years(range0.4–18.6)years,19CNSrelapsesoccurred(7,11and1ingroups1-3respectively).The3-yearactuarialincidenceofCNSrelapsewas17.6,7.3%and2.4%ingroups1,2and3respectively(P=0.026).The3-yeareventfreesurvival(EFS)was70%,83%and70%inGroups1–3,respectively(P=0.15).PtsreceivingITMTX,therewasatrendtowardreductioninCNSrelapseforptsreceiving4-6dosesofITMTXcomparedto1-3(P=0.052)andpatientsreceivingtheirfirstdoseofITMTXwithinsevendaysofdiagnosis(P=0.08).NewApproachforR/RDLBCL

in2013ASHIncorporatingHigh-DoseIVMethotrexateIntoInitialTherapyResultsInLowerRatesOfCentralNervousSystem(CNS)RelapseInPatientsWithHigh-Risk(DLBCL)Conclusion:TheuseofIVMTXanddose-intensechemotherapywasassociatedwithlowerincidenceofCNSrelapsecomparedwithITchemotherapyalone.NewApproachforR/RDLBCL

in2013ASHWeeklyTemsirolimusandBortezomibForRelapsedOrRefractoryB-CellNon-HodgkinLymphoma:AWisconsinOncologyNetworkPhaseIIStudyProteosomeinhibitorsandmammaliantargetofrapamycin(mTOR)inhibitorsareeachknowntohaveactivityforvariousB-cellmalignancies,andaffectdistinctcellularpathways.ThestudyconductedaphaseIItrialoftemsirolimusandbortezomibinrelapsedandrefractoryB-cellNHL,usingaweeklydosingschemethatwaspreviouslytestedinmultiplemyeloma.39patientswereenrolled.A35daycyclewasemployedwithbortezomibgivenat1.6mg/m2andtemsirolimusgivenat25mgIVweeklyondays1,8,15,and22.Initiallytemsirolimuswasalsogivenonday29but,duetoahighrateofthrombocytopenia,afterthefirst14patientswereenrolledtheprotocolwasamendedandtheday29temsirolimusdosewasremoved.NewAgentsInDLBCL

In2013ASHPhaseIIRandomizedStudyOfLenalidomideOrLenalidomideandRituximabAsMaintenanceTherapyFollowingStandardChemotherapyForPatientsWithIntermediate-High/HighRiskDiffuseLargeB-CellLymphoma(DLBCL)Lenalidomide(len),animmunomodulatorydrug,hasactivityinrelapseddiffuselargeBcellLymphoma.Lenenhancesthenatural-killercellmediatedantibody-dependantcellularcytotoxicityofrituximabinlymphomacelllinesandinhibitsangiogenesisaswellasalterscytokineproduction.Intermediate-high/highriskIPIptswithDLBCLwererandomizedtolen(armA)aloneorlenandrituximab(armB).PtsinarmAreceivedlenatadoseof25mgdailyfor21daysof28days.PatientsonarmBreceivedlenatadoseof20mgdailyfor21daysof28daysalongwithrituximabonday8ofevencycles.NewApproachforR/RDLBCL

in2013ASHFortythreepts,21armA/22armB,21female/22male,withamedianageof59yrswereenrolled.ThemedianIPIwas4forptsovertheageof60andthemedianaa-IPIwas3.ThreeptsreceivedXRTtoareasofbulkydisease.Atamedianfollowupof27months,the2yrDFSandOSwas88%.ForpatientsinarmAandarmBthe2yrDFSwas90%vs.86%

andthe2yrOSwas95.2%vs.81%.Twoptsdiscontinuedtreatmentduetoadverseevents.Grade3-4toxicitiesincludeneutropenia(28%),fatigue(16%),diarrhea(6%),DVT(3%),rash(3%),febrileneutropenia(3%).Relatedgrade1-2toxicitiesincludehypothyroidism(15%)andrash(54%).NewApproachforR/RDLBCL

in2013ASHConclusions:LenasmaintenancetherapydemonstratesclinicalactivityfollowingstandardchemotherapyandimprovesDFSandOSinDLBCLpatientswithhighriskprognosticfeaturesascomparedwithhistoricalcontrols.NewAgentsInDLBCL

In2013ASHSafetyandEfficacyOfObinutuzumab