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CureforMantleCellLymphomaWithinReach,SaysExpert

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Medscape Medical News > Oncology

Cure for Mantle Cell Lymphoma Within Reach, Says

Expert
Fran Lowry
January19,2016
Comment

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Bortezomib Works Firstline in Mantle Cell

Lymphoma
Ibrutinib: A Step Change
in the Treatment of MCL

Standard of Care in
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Thereviewemphasizesthefactthatpatientageand
comorbiditiesaretheprimaryfactorsthatshoulddictatethe
initialapproachtotreatment.
IntensiveTherapyforYoung,FitPatients
ForpatientswithMCLwhoareaged65yearsoryoungerand
whoarewithoutsignificantcomorbidities,thebestresultshave
beenseenwithintensivetherapywithregimensthatcontain
highdosecytarabine(HDAC)consolidatedwithhighdose
chemotherapyandautologousstemcelltransplantation
(ASCT).
WhenASCTisplanned,theoptionsforinductionincludethe
NordicLymphomaGroupMCL2regimen(rituximabwithdose
escalatedcyclophosphamideanddoxorubicin,vincristine,
prednisone[RmaxiCHOP]alternatingwithHDAC)and
alternatingcyclesofRCHOPanddexamethasone,cisplatin,
cytarabine(DHAP).
AnalternativeapproachwithoutASCTforyounger,fitpatients
ishyperfractionatedcyclophosphamide,vincristine,
doxorubicin,dexamethasonealternatingwithhighdose
methotrexate,andcytarabinewithrituximab(Rhyper
CVAD/MA).

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"Thesetwointensivetherapieshaveproducedoverallsurvival
exceeding10years.Suchoverallsurvivalhasnotbeen
achievedbysalvagetherapies,suchasRCHOPor
bendamustine,"DrWangsaid.

"Thisisbasedonthetheory
thatmantlecelllymphomaismostvulnerabletofrontlineattack.Thisis
mostimportantforyoungandfitpatients.Ifyoumessupwiththe
frontlinetherapy,youhavemissedthechanceforlongtermremission.
Ifyougiveyoung,fitpatientssalvagetherapy,theirdiseasewillrelapse
quickly,theywillgetintoapatternofconstanttherapies,andtheywill
diefromtheirdiseasemuchsoonerthan10years,"hesaid.

If you mess up

with the frontline

therapy, you have
missed the chance
for long-term
remission.
DrMichaelL.Wang

Toimproveonthetolerabilityofsuchintensivetherapy,MDAnderson

hasdesignedaphase2studyinyounger,treatmentnaivepatientsthat
usesaleadinchemotherapyfreewindowperiodwithrituximaband
ibrutinibfor6to12monthsfollowedbyabbreviated,responseadaptedRhyperCVAD/MA,DrWang
said.
"Theaimofthisstudyistokeepthesameefficacyoftheintensivetherapiesbuttodramatically
decreasetheirtoxicities.Afterweusetherituximabandibrutinib,thenthechemotherapywillbecutfrom
68cyclesto46cycles,"hesaid.
IntensivetherapyistootoxicforpatientswithMCLwhoareolderthan65yearsatdiagnosis.Forthese
patients,thechoicescurrentlyareRCHOPfollowedbymaintenancerituximabor

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23/11/2016

CureforMantleCellLymphomaWithinReach,SaysExpert

bendamustine/rituximab(BR)salvagetherapies,DrWangsaid.
However,RCHOPandBRarebeingphasedout,becausebettertherapeuticchoiceshaveemergedfor
thisgroupofpatients.
"RCHOPplusibutrinibisshowinggoodresults.Also,bendamustine/rituximabplusibutrinibisbeing
studiedinphase3clinicaltrialsin550patientsfrom350centersworldwide.Resultsareexpectedtobe
availableinthemiddleof2016,"hesaid.
MedianSurvivalHasBeenDoubled
"Wehavemadesomuchprogressintreatingmantlecelllymphoma.Itusedtohaveamediansurvivalof
3to5years,butinyoungerpatientstreatedwithintensiveregimens,theoverallsurvivalnowexceeds
10years,"DrWangsaid.
Inelderlypatients,thegainshavenotbeenasdramatic,buttheuseofmaintenancerituximabafterR
CHOPresultsina4yearoverallsurvivalof79%.BRappearsatleastaseffectiveandhaslesstoxicity,
althoughlongerfollowupisneededtoestablishtheimpactofBRonoverallsurvival,asarestudiesthat
confirmsurvivalbenefitfromrituximabmaintenanceafterBR.
"Advancesinthetreatmentofpatientswithrelapsed/refractoryMCLhavebeenmadewiththeapproval
ofbortezomib,lenalidomide,andibrutinib.Theseagentsarenowincorporatedintofrontlinetreatment
strategiesandshouldfurtherimproveresponseratesandsurvival,"hesaid.
DrWanghasfinancialrelationshipswithJanssenPharmaceuticals,AcertaPhrma,Celltrion,
Pharmacyclics,andOnyx.
JClinOncol.PublishedonlineJanuary11,2016.Abstract

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