ESMO指南中的DLBCL预后指数

DLBCLPrognosticIndicesfromPerspectiveofESMOGuidelinesZhitaoYing,M.D.PekingUniversityCancerHospitalMar-18,2017Outcome

of

Patients

with

DLBCL

after

R-CHOP

ChemotherapyCoffier

B,

et

al.

Hematology,

2016:

366-378.TreatmentHistoryofDLBCLClinicalPrognosticFactorsAge>60PS≥2LDH>1xnormalStageIIIorIV>1extranodalsiteIPIPS

≥2LDH>1xnormalStageIIIorIVaa-IPINEJM,

1993,

329(14):

987-94.

Clinical

Factors

are

Still

Prognostic

in

Rituximab

EraPFSOSSehn

LH,

et

al.

Blood,

2007,

109:

1857-1861.IPI

is

Recommended

in

ESMO

GuidelinesTilly

H,

et

al.

Ann

Oncol.

2015,

26

(Suppl

5):

v116-125IPILow-riskDLBCL

Patient

Relapsedafter

R-CHOPCellofOrigin(COO)DeterminestheOutcomeRosenwaldA,etal.NEnglJMed2002;346:1937-1947.Pre-rituximab

eraRituximab

eraPrognosticValueofCOOisIndependentofIPIGCB

(N=115)Type

3

(N=52)ACB

(N=73)P

ValueRisk

Group0.44Low

(0-1)404129Intermediate

(2-3)494351High

(4-5)111519RosenwaldA,etal.NEnglJMed2002;346:1937-1947.Alizadeh

AA,

et

al.

Nature,

2000;

403:

503-511.IPI

0-2IPI

3-5Randomizedphase2open-labelstudyof

R-CHOP±bortezomibinpatientswithuntreatednon-germinalcenterB-cell-likesubtypediffuselargecelllymphoma:

ResultsfromthePYRAMIDtrial(NCT00931918)JPLeonard,KKolibaba,JAReeves,

ATulpule,IWFlinn,TKolevska,

RRobles,CFlowers,RCollins,NJDiBella,SWPapish,PVenugopal,

AHorodner,

ATabatabai,JHajdenberg,GMulligan,RNeuwirth,

KSuryanarayan,D-LEsseltine,SdeVosStudydesignECOGPS,EasternCooperativeOncologyGroupperformancestatus;IHC,immunohistochemistry;IV,intravenous;

PO,oraladministrationArmA(n=95)Bortezomib1.3mg/m2IV,Days1and4R-CHOP†21X6cyclesArmB(n=95)R-CHOP†21X6cyclesNon-GCBSelectionPreviouslyuntreatedDLBCLMeasurablediseaseECOGPS0–2IHCalgorithmAssay/scoringinrealtimeatcentralUSlab*Hansmethod1

(CD10,bcl-6,MUM-1)48–72hourturnaroundRetrospectivemolecularanalysesofRNApatterns,DNAmutationsRANDOMIZE*LocalIHCtestingbycertifiedlocalpathologistswasalsoemployed,confirmedbycentralreview;

†R-CHOPstandarddose(rituximab375mg/m2,cyclophosphamide750mg/m2,doxorubicin

50mg/m2,vincristine1.4mg/m2[max2mg],allIVonDay1,andprednisone100mgPOonDays1–5)

HansCP,etal.Blood2004;103:275–82FPI:Oct2009LPI:July20132-yearPFS:78%R-CHOPvs82%VR-CHOPHR(95%CI):0.73(0.43,1.24);p=0.611Progression-freesurvivalCI,confidenceinterval;HR,hazardratio;

PFS,progression-freesurvival(timefromrandomizationtoinvestigator-assessedprogressionordeath)Patientsatrisk:R-CHOPVR-CHOPPFSprobabilityTimetoevent(months)0.00.10.20.30.40.50.60.70.80.91.00510152025303550556065707540459192727565726166576150513738282757220201000022241513Treatmentgroup:Censoredobservations:R-CHOPVR-CHOPR-CHOPVR-CHOPR-CHOP

(N=91)

25%EventsVR-CHOP

(N=92)

18%Overallsurvival2-yearOS:88%R-CHOPvs93%VR-CHOPHR(95%CI),0.75(0.38,1.45);p=0.763

OS,overallsurvival(timefromrandomizationtodeath)Patientsatrisk:R-CHOPVR-CHOPTimetoevent(months)91928288808575837380646847493538613340301000028332023OSprobability0.00.10.20.30.40.50.60.70.80.91.0Treatmentgroup:Censoredobservations:R-CHOPVR-CHOPR-CHOPVR-CHOPR-CHOP

(N=91)

15%EventsVR-CHOP

(N=92)

12%05101520253035505560657075404514AndrewJDavies1,JoshCaddy2,TomMaishman2,SharonBarrans3,ChristophMamot4,MatthewCare5,ChristopherPocock6,LouiseStanton,2,DebbieHamid2,KeithPugh2,AndrewMcMillan,7,PaulFields8,AntonKruger9,AndrewJack10andPeterW.M.Johnson1AProspectiveRandomisedTrialofTargetedTherapyforDiffuseLargeB-CellLymphoma(DLBCL)BaseduponReal-TimeGeneExpressionProfiling.TheREMoDL-BStudyoftheUKNCRIandSAKKLymphomaGroups1CancerResearchUKCentre,UniversityofSouthampton,Southampton,UnitedKingdom2SouthamptonClinicalTrialsUnit,UniversityofSouthampton,Southampton,UnitedKingdom3StJamesInstituteofOncology,HMDS,Leeds,UnitedKingdom4,CantonalHospitalofAarau,Aarau,Switzerland5UniversityofLeeds,LeedsInstituteofCancerandPathology,Leeds,UnitedKingdom6EastKentHospitals,Canterbury,UnitedKingdom7NottinghamCityHospital,Nottingham,UnitedKingdom8DepartmentofHaematology,Guy'sandStThomas'HospitalsNHSTrust,London,UnitedKingdom9RoyalCornwallHospital,Truro,UnitedKingdom10HMDS,LeedsCancerCentre,LeedsTeachingHospitalsNHSTrust,Leeds,UnitedKingdomREMoDL-BREMoDL-Bstudy(UK)

RandomizedevaluationofmolecularguidedtherapyinDLBCLwithBortezomibAllpatientsinitiallyrandomized,designedtocloseforGCBsubjectsifevidenceoffutilityUpto940subjects,minimum260ABCsubtype(April2011–2020)ClinicalTIdentifier:NCT01324596DLBCLdiagnosis&subtypingR-CHOPx1cycleRR-CHOPSixcyclesoftreatment(3weekspercycle)RB-CHOPcycles2-6oftreatment(3weekspercycle)BxGEPNonrandom.ABCGCBUnclass.Responserate(%):MolecularprofileandarmPRCR/CR(u)90.2%87.7%88.0%87.5%90.5%96.3%81.8%R-CHOP-Ibrutinib

for

Patients

with

B-NHLYounes

A,

et

al.

LancetOncol2014;15:1019–1026.Outcomes

of

DLBCL

Patients:

R2-CHOP

vs.

R-CHOP

(Phase

II

study)Nowakowski

GS,

et

al.

J

Clin

Oncol,

2015,

33(3):

251-257.

OngoingClinicalTrialsEvaluatingNewStrategiesinNon-GCBDLBCLPHOENIXIHCROBUSTThe

distinction

between

GCB-like

subtype

and

ABC-like

subtype,studiedbyGEPandsuggestedbyIHCdonotinfluencetreatmentchoicesatthemoment.

TillyH,etal.AnnOncol,2012,23;(Suppl7):vii78-82.TheABC

subtype

has

been

shown

to

have

a

worse

prognosis

when

compared

with

GCB

in

patients

treated

by

R-CHOP.At

present

time,

pending

results

of

large

comparative

studies,none

of

these

agents

are

appropriate

for

routine

therapy

in

practice.DA-EPOCHR-CHOP-BortezomibR2-CHOPR-CHOP-Ibrutinib

Tilly

H,

et

al.

Ann

Oncol,2015,

26

(Suppl

5):

v116-125.MYC基因重排能够预测DLBCL预后11/14

Bcl2+11/14

Bcl2+K;apper

W,

et

al.

Leukemia,

2008(22):

2226-2229Savage

KJ,

et

al.

Blood,

2009,

114(17):

3533-3537.

8/12

Bcl2+R

eraPre-Rera8/12

Bcl2+PoorOutcomeofDHL(MYC+/BCL2+)DHLDLBCLBLSnuderl

M,

et

al.

Am

J

Surg

Patho,2010,

34(3):

327-340.DHL:

the

MDACCExperienceOki

Y,

et

al.

BrJHaematol.2014;166(6):891-901.R-EPOCH

is

Associated

with

a

better

PFS

(SystemicReviewandMeta-analysis)Howlett

C,et

al.BrJHaematol.2015;170(4):504-514.IHC

=

FISH？Johnson

NA,

et

al.

J

Clin

Oncol,

2012:

30(28):

3452-3459DHITOtherMYC+/BCL2+NoMYC+/BCL2+CutoffMYC

IHCCutoffBCL2

IHCPrognosisMYCPrognosisBCL2Green,JCO

201213518%≥40%≥70%nonoJohnson

N,

JCO

201218629%≥40%≥50%noyesHorn

H,

Blood

201314128%≥40%≥1%yesyesHu

S,

Blood

201346634%≥40%≥70%nonoValera,

Hematologica201312027%≥10%≥50%yesyesPerry

AM,

bjh,

201431127%>50%>30%yesyesAlthoughR-CHOPgivespooroutcomes

fordouble-hitlymphomas,onlypreliminaryresultshavesuggested

betterresultswithmoreintensiveregimens,andclinical

trialsarerequiredinthissubtype.

Tilly

H,

et

al.

Ann

Oncol,2015,

26

(Suppl

5):

v116-125.Definition

of

HGBL

in

2016

WHO

ClassificationSwerdlow

SH,

et

al.

Blood.2016,

127(20):

2375-2390OutcomesDifferwithDifferentDiseaseLocationsIELSG-INTERNATIONALEXTRANODALLYMPHOMASTUDY

GROUPNeedtoFocusonDifferentPathologySubtypesSwerdlow

SH,

et

al.

Blood.2016,

127(20):

2375-2390Recommended

Treatment

Strategies

for

DLBCL

in

ESMO

GuidelinesTilly

H,

et

al.

Ann

Oncol.

2015,

26

(Suppl

5):

v116-125HaiounC,

et

al.

Blood.2005;106(4):1376-81.DupuisJ,

et

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AnnOncol2009;20:503-507.InterimPETisaPowerfulTooltoPr