Treatment: Gastric MALT lymphoma. Stathis.pdf · LP/MM and/or SM; no LEL rRD Responding Focal empty...
Transcript of Treatment: Gastric MALT lymphoma. Stathis.pdf · LP/MM and/or SM; no LEL rRD Responding Focal empty...
AnastasiosStathis,M.D.PhaseIandLymphomaUnit
OncologyIns6tuteofSouthernSwitzerlandBellinzona,Switzerland
Treatment:GastricMALTlymphoma
GastricMALTlymphoma
• MALTlymphomas:approximately7%ofallNHLs• Atleast1/3presentasaprimarygastriclymphoma
• 2/3ofcasesassociatedwithH.pyloriinfec6on
ESMOClinicalPrac>ceGuidelines,2013
Openques>onsinthemanagementofgastricMALTlymphoma
• stagingprocedures• H.pylorieradica6ontoallpa6ents?• secondlinetreatments
Openques>onsinthemanagementofgastricMALTlymphoma
• stagingprocedures• H.pylorieradica6ontoallpa6ents?• secondlinetreatments
MandatorystagingproceduresinMALTlymphomaatanysite
• Historyandphysicalexam(includinglymphnoderegions,eyeandENTareas,liverandspleen)
• Completebloodcountsandbasicbiochemicalstudies(includingrenalandliverfunc6on,LDHandβ2MG,serumIFE,HIV,HCVandHBVserology)
• CTofthechest,abdomenandpelvis.• bonemarrowaspirateandbiopsyrecommended• ThevalueofPETiscontroversialandhasuncertainclinicalu6lity
ESMOConsensusConference,AnnOncol2013
RecommendedproceduresingastricMALTlymphoma
• EGDwithmul6plebiopsies• histochemicalexamina6onforH.pyloriandserologystudiesifhistologyisnega6ve
• endoscopicultrasoundtoevaluatetheregionallymphnodesandgastricwallinfiltra6on
• op6onal:FISHforthet(11;18)transloca6on
EGILSConsensusReport,2011ESMOClinicalPrac>ceGuidelines,2013
§ The value of PET is controversial and has uncertain clinical utility
§ multifocal disease in ≥25% of cases
§ variable FDG-avidity (higher in non-gastric lesions!)
§ pooled PET/CT detection rate, 71% (95% CI: 61-80%) in a literature meta-analysis
Staging of MALT Lymphoma
Treglia et al. Hematol Oncol. 2015
Lower FDG-avidity in gastric & OA lesions
Treglia et al. Hematol Oncol. 2015 Sep;33(3):113-24
Openques>onsinthemanagementofgastricMALTlymphoma
• stagingprocedures• H.pylorieradica>ontoallpa>ents?• secondlinetreatments
MostgastricMALTlymphomasregressaLerH.pylorieradica>on
Bertoni & Zucca, Lymphomas: Essentials for Clinicians 2015: 55-60
Theproblemoftheresponsedefini>on
Score Descrip>on HistologicFeatures
CR CompleteRemission NormaloremptyLPand/orfibrosis withabsentorsca]eredplasmacellsand lymphoidcellsintheLP;noLEL
pMRD ProbableMinimal EmptyLPand/orfibrosiswithaggregatesofResidualDisease lymphoidcellsorlymphoidnodulesinthe LP/MMand/orSM;noLEL
rRD Responding FocalemptyLPand/orfibrosis;dense,diffuseResidualDisease ornodularlymphoidinfiltrate,extending aroundglandsintheLP.FocalLELorabsent
NC NoChange Dense,diffuseornodularlymphoidinfiltrate withLEL(LEL‘‘maybeabsent’’)
GELAscoreforlymphomaresponseevalua>onaLerHpylorieradica>on
Copie-Bergmanetal,Gut2003;Copie-Bergmanetal,BrJHaematol2012
LP=laminapropria;LEL=lymphoepitheliallesions;MM=muscularismucosa;SM=submucosa
Endoscopicandhistologicalremissiondoesnotmean“cure”
• 54pa6entswithmonoclonalityatdiagnosis• 42(77%)histologicremission
– 56%molecularremission(byPCR)– 44%sustainedmolecularremission(medianf-up,2years)– 6(14%)histologicrelapses(4/6inthepresenceofmoleculardisease)
• clinicalandprognos6crelevanceofmolecularremissions6lltobeascertained
Bertonietal.Blood2002
Long-termoutcomeaLerH.pylorieradica>on(IOSIandVareseseries)
A.Stathisetal.AnnOncol,2009
• N=105,stageIE• f-up,76mos
• Remissionrate,76%
• Long-termclinicalcontrolinmostcases:
• 43%ofrespondershadhistologicalscorefluctua6ons
• 57%hadstableMRD
• 5-yearOSis92%.
Long-termsurveysaLerH.pylorieradica>on
Wundischetal.JCO,2005Fischbachetal.Gut,2007
Stathisetal.AnnOncol,2009Nakamuraetal.Gut2012
• notonlypa6entswithmolecularresidualdiseasemayremainstablebutalsothosewithminimalhistologicalMALTlymphomaresiduals
• Awatchandwaitpolicyseemssafeinpa6entswithminimalhRDorhistological-onlylocalrelapse
HPeradica>onisthestandardini>altreatmentforlocalizeddisease
EGILSConsensusReport,2011ESMOClinicalPrac>ceGuidelines,2013
WhytotreatHP-nega>vepa>ents?
• Falsenega6vediagnos6ctest• Othermicroorganismsinvolved(H.heilmannii)
• Responsesin14of72publishedcases(19%)EGILSConsensusReport
HPeradica>onisthestandardini>altreatmentforlocalizeddisease
• H.pylorieradica6ontherapymustbegiventoallgastricMALTlymphomas,independentlyofstage
• Responsesmayrequireupto12monthsormore
• HP-nega6vepa6entswithgastricMALTlymphomamayalsoreceivean6-Hpyloritreatment
• Lymphomaswitht(11;18)andthosewithlymphnodeinvolvementareunlikelytoregressamerHPeradica6on EGILSConsensusReport,2011
ESMOClinicalPrac>ceGuidelines,2013
Openques>onsinthemanagementofgastricMALTlymphoma
• stagingprocedures• H.pylorieradica6ontoallpa6ents?• secondlinetreatments
SameoutcomeaLerdifferenttreatmentsinstageIEgastricMALTlymphoma
Treatment N°ofpts CRrate 5-yearsOS(95%Cl)
An6bio6cs 45 67% 94%(65-99)Localtreatmenta 14 100% 92%(57-99)Chemotherapy 8 50% 75%(32-93)Combinedmodality
b 5 100% 80%(20-97)
Total 72 74% 89%(76-96)
asurgery±RTbsurgery+adjuvantchemotherapy Pino=etal,LeukLymphoma1997
Bertoni&Zucca.Lymphomas:Essen6alsforClinicians2015
RTisveryac>veinMALTlymphoma
Bertoni&Zucca.Lymphomas:Essen6alsforClinicians2015
RTisveryac>veinMALTlymphoma
• op>malRTvolume,doseandtechnique?• doesthisreallytranslatetocure?• inaveryindolentcondi>on,isthepoten>altoxicityacceptable?
• longtermsafety?(malignancy,gastricandrenaltoxicity)
Long-termoutcomeofgastricMALTlymphomaaLerRT:Theretrospec>vemul>-centreIELSG-22study
WirthAetal.AnnOncol2013
medianRTdosetostomach,40Gy(26–46Gy)
Chemotherapy in MALT lymphomas
Treatment Nr. pts ORR CR Author
Alkylators 24 pts 100% 75% Hammel P. J Clin Oncol 1995
R-CHOP/CNOP 7 pts 100% 100% Raderer M. Ann Oncol 2002
Cladribine 26 pts 100% 84% Jäger G. J Clin Oncol 2002
Oxaliplatin 16 pts 93% 56% Raderer M. J Clin Oncol 2005
Fluda-Mito 20 pts 100% 100% Zinzani PL. Cancer 2004
R-cladribine 39 pts 81% 58% Troch M. Haematologica 2013
responsen%ORR 2573 SD 618PD 39
Rituximabac>vityinMALTlymphoma
IELSGphaseIIstudy,Conconietal.Blood2003
34pts,11withpriorchemotherapy,15gastric,20stageIV
401evalua
blepa>
ents
IELSG-19 Randomised Study Treatment Schedule 19
E. Zucca E et al. J Clin Oncol 2017 Epub
E. Zucca E et al. J Clin Oncol 2017 Epub
IELSG-19 Randomised Study Final Results 19
E. Zucca E et al. J Clin Oncol 2017 Epub
IELSG-19 Randomised Study Outcome by Primary Site 19
AnyroleforR-maintenance?IELSG-38:studydesign38
• Single arm phase II study
• R-Chlorambucil for 6 mos followed by 2-yrs maintenance with Rsc
• Accrual completed with 112 newly diagnosed MALT pts in need of systemic treatment
Response-adapted1stlineR-Benda(GELTAMOMZLphase-2trial)
A. Salar et al, Lancet Oncol, 2014
Targeting BTK with ibrutinib in r/r MZL
NoyAetal.Blood2017
Median, 14 months
62% at 18 months
80% at 30 months
PhaseIIstudiesinMALTlymphoma
Take-homemessages
• H.pylorieradica6onisstandardfront-linetreatment
• PersistentMRDnotclearlyassociatedwithprogression
• Watchfulwai6ngissafeincaseofstableMRDortransientlocalhistologicalrelapses
• ThebesttreatmentnotyetdefinedforHP-nega6vecasesandan6bio6cfailures
LY03trialofgastricMALTlymphoma
B.Hancock,etal.BrJHaematol,2009
chlorambucil vs. observation after anti-Helicobacter therapy
• CRtobeconfirmedin2subsequentinves6ga6ons
• PRandSDandrelapsestobeclinicallymanagedonanindividualbasis:
– ifnosignsofendoscopicorclinicalprogressionareevident,a‘watchandwait’strategycanbeadopted
– pa6entswithdistantdissemina6onand/orgrossendoscopictumourshouldreceiveoncologicaltreatment.
EGILSrecommenda>onsforrestagingandfollow-up
EGILSConsensusReport
• ClearevidenceofEUSu6lityasastagingprocedurebutlessstrongevidenceinfollow-up
• Breathtest±EGDat~3mos.ameran6bio6csthenEGDwithbiopsiesq6msx2years,thenq12mos
• Molecularstudiesnotneeded
HowtofollowupaLeran>bio>cs?
EGILSConsensusReport
HowlongtofollowupaLeran>bio>cs?
Life-long?Pa6entswithgastricMALTlymphomahavea66meshigherriskforgastricadenocarcinomaincomparisonwiththegeneralpopula6onandtheriskishighestinpa6entsyoungerthan60
Capelleetal.EurJCancer,2008