ResearchToPractice.com/RTPODMM2014 1

Multiple Myeloma

TARGET AUDIENCEThisactivityisintendedformedicaloncologists,hematology-oncologyfellowsandotherhealthcareprovidersinvolvedinthetreatmentofmultiplemyeloma(MM).

OVERVIEW OF ACTIVITYMMisaplasmacellneoplasmthataccountsforapproxi-mately10%ofallhematologiccancers.Itisestimatedthat24,050newcaseswillbediagnosedand11,090deathswilloccurintheUnitedStatesin2014.Patientswithsmoldering(asymptomatic)orStageIactivemyelomamaybeobserved,astheyoftenhaveanindolentdiseasecourseformanyyearswithouttherapy,althoughthisparadigmmaybechangingforthoseconsideredtobeathighrisk.Ontheotherhand,thediseasecourseforadvancedmyelomaisuniformlyaggressive.Theintroductionofnewagentswithsubstantialactivityhasimprovedoutcomesandallowedpatientstoexperiencelongerperiodsofremission.Bothnovelproteasomeinhibitorsandimmunomodulatory(IMiD)agentshaveeffectivelytransformedthestandardtreatmentforpatientswithnewlydiagnosedandrelapsed/refractoryMM.Thus,thecurrentchallengefacingtheoncologycommunityisidentifyingthosepatientswhowillobtainthegreatestbenefitfromaspecificregimenwhileincurringtheleasttoxicity.

Forthisreason,hematologiconcologistsmustbeapprisedoftheuniquerisksandbenefitsaccompanyingeachevidence-basedtreatmentstrategyandoftheacceptablemonitoringandsupportivemanagementtechniquesthatenableearlyrecognitionofsafetyconcernsandeffectiveinterventionstoaddresssideeffects.Despitetheexistenceofanumberoftoolstoassistcliniciansinthisregard,manyareasofcontro-versypersistwithinacademicandcommunitysettings.Thisprogramusesareviewofrecentpublicationsandpresenta-tions,facultycasesandQ&Asessionstoassistmedicaloncol-ogists,hematology-oncologyfellowsandotherhealthcareproviderswiththeformulationofup-to-dateclinicalmanage-mentstrategiesforMM.

LEARNING OBJECTIVES• Recallexistingandemergingclinicalresearchdata

toeffectivelyimplementevidence-basedtherapeuticapproachesforpatientswithnewlydiagnosedandrelapsed/refractoryMM.

• Recognizeessentialpatientcareconsiderationswiththeuseofproteasomeinhibitor-and/orIMiD-containingsystemictherapiesinnewlydiagnosedMM.

• Examineoptimaldurationandbenefits/risksoflenalid-omidemaintenancetherapyafterstemcelltransplantationforpatientswithactiveMM.

• Assesstheuseofbone-targetedtherapyinpatientswithnewlydiagnosedMMregardlessofthepresenceofdiseaseinthebone.

• Recallnewdatawithnoveltreatmentapproacheswithhistonedeacetylaseinhibitorsormonoclonalantibodiesforrelapsedand/orrefractoryMM.

• AppraiseemergingclinicaltrialdatawithproteasomeinhibitorsandtyrosinekinaseinhibitorsastreatmentforWaldenströmmacroglobulinemia.

• Developarisk-adaptedtreatmentplanforpatientswithsmolderingMM.

• AssesstheongoingclinicaltrialsevaluatingtherapeuticapproachesforMM,andcounselappropriatelyselectedpatientsforstudyparticipation.

ACCREDITATION STATEMENTResearchToPracticeisaccreditedbytheAccredita-tionCouncilforContinuingMedicalEducationtoprovidecontinuingmedicaleducationforphysicians.

CREDIT DESIGNATION STATEMENT ResearchToPracticedesignatesthisenduringmaterialforamaximumof2AMA PRA Category 1 Credits™.Physiciansshouldclaimonlythecreditcommensuratewiththeextentoftheirparticipationintheactivity.

HOW TO USE THIS CME ACTIVITYThisCMEactivityconsistsofavideocomponent.Toreceivecredit,theparticipantshouldwatchthevideo,completethePost-testwithascoreof75%orbetterandfillouttheEducationalAssessmentandCreditFormlocatedatResearchToPractice.com/RTPODMM2014/CME.

C M E I n f o r m a t i o n

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CONTENT VALIDATION AND DISCLOSURESResearchToPractice(RTP)iscommittedtoprovidingitsparticipantswithhigh-quality,unbiasedandstate-of-the-arteducation.Weassesspotentialconflictsofinterestwithfaculty,plannersandmanagersofCMEactivities.Realorapparentconflictsofinterestareidentifiedandresolvedthroughaconflictofinterestresolutionprocess.Inaddition,allactivitycontentisreviewedbybothamemberoftheRTPscientificstaffandanexternal,independentphysicianreviewerforfairbalance,scientificobjectivityofstudiesrefer-encedandpatientcarerecommendations.

FACULTY—Thefollowingfaculty(andtheirspouses/partners)reportedrealorapparentconflictsofinterest,whichhavebeenresolvedthroughaconflictofinterestresolutionprocess:

Irene M Ghobrial, MDAssistantProfessorinMedicineDana-FarberCancerInstituteHarvardMedicalSchoolBoston,Massachusetts

Advisory Committee: Bristol-MyersSquibbCompany,CelgeneCorporation,GenzymeCorporation,Millennium:TheTakedaOncologyCompany,NovartisPharmaceuticalsCorporation,OnyxPharmaceuticalsInc.

Ola Landgren, MD, PhDChief,MyelomaServiceMemorialSloan-KetteringCancerCenterNewYork,NewYork

ContractedResearch:CelgeneCorporation,OnyxPharmaceu-ticalsInc.

MODERATOR—DrLoveispresidentandCEOofResearchToPractice,whichreceivesfundsintheformofeducationalgrantstodevelopCMEactivitiesfromthefollowingcommer-cialinterests:AbbVieInc,AlgetaUS,AmgenInc,Astellas,AstraZenecaPharmaceuticalsLP,AveoPharmaceuticals,BayerHealthCarePharmaceuticals,BiodesixInc,BiogenIdec,BoehringerIngelheimPharmaceuticalsInc,Bristol-Myers

SquibbCompany,CelgeneCorporation,DaiichiSankyoInc,DendreonCorporation,EisaiInc,ExelixisInc,GenentechBioOncology,GenomicHealthInc,GileadSciencesInc,IncyteCorporation,Lilly,MedivationInc,Merck,Millennium:TheTakedaOncologyCompany,NovartisPharmaceuticalsCorpo-ration,Novocure,OnyxPharmaceuticalsInc,PrometheusLaboratoriesInc,RegeneronPharmaceuticals,Sanofi,SeattleGenetics,SpectrumPharmaceuticalsInc,TevaOncologyandVisionGateInc.

RESEARCH TO PRACTICE STAFF AND EXTERNAL REVIEWERS—ThescientificstaffandreviewersforResearchToPracticehavenorealorapparentconflictsofinteresttodisclose.

This educational activity contains discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indica-tions. Please refer to the official prescribing information for each product for discussion of approved indications, contra-indications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

ThisactivityissupportedbyeducationalgrantsfromMillen-nium:TheTakedaOncologyCompany,NovartisPharmaceuti-calsCorporationandOnyxPharmaceuticalsInc.

Hardware/Software Requirements: Ahigh-speedInternetconnectionAmonitorsetto1280x1024pixelsormoreInternetExplorer7orlater,Firefox3.0orlater,Chrome,Safari3.0orlaterAdobeFlashPlayer10.2plug-inorlaterAdobeAcrobatReader(Optional)Soundcardandspeakersforaudio

Last review date: May2014

Expiration date:May2015

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S e l e c t P u b l i c a t i o n s

A multicenter, randomized, double blind, placebo controlled phase III study of panobinostat in combination with bortezomib and dexamethasone in patients with relapsed multiple myeloma. NCT01023308

A phase II study of modified lenalidomide, bortezomib and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma. NCT01782963

AttalMetal.Lenalidomide maintenance after stem-cell transplantation for multiple myeloma: Follow-up analysis of the IFM 2005-02 trial. Proc ASH 2013;Abstract 406.

AttalMetal.Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med 2012;366(19):1782-91.

BolliNetal.Whole exome sequencing of multiple myeloma reveals an heterogeneous clonal architecture and genomic evolu-tion. Proc ASH2013;Abstract 399.

BringhenSetal.A phase II study with carfilzomib, cyclophosphamide and dexamethasone (CCd) for newly diagnosed multiple myeloma. Proc ASH 2013;Abstract 685.

BrioliAetal.Serum free light chain escape in progression and treatment resistance in multiple myeloma: A marker for the impact of intra-clonal heterogeneity. Proc ASH 2013;Abstract 752.

FaconTetal.Initial phase 3 results of the first (frontline investigation of lenalidomide + dexamethasone versus standard thalidomide) trial (MM-020/IFM 07 01) in newly diagnosed multiple myeloma (NDMM) patients (pts) ineligible for stem cell transplantation (SCT). Proc ASH2013;Abstract 2.

FostierKetal.Carfilzomib: A novel treatment in relapsed and refractory multiple myeloma.OncoTargets and Therapy 2012;5:237-44.

IFM2005-02:Relevance of maintenance therapy using lenalidomide (Revimid®) after autologous stem cell transplantation patients under the age of 65. (Open, randomised, multi-centric trial versus placebo). NCT00430365

JasielecJetal.Predictors of treatment outcome with the combination of carfilzomib, lenalidomide, and low-dose dexametha-sone (CRd) in newly diagnosed multiple myeloma (NDMM). Proc ASH 2013;Abstract 3220.

KordeNetal.Phase II clinical and correlative study of carfilzomib, lenalidomide, and dexamethasone followed by lenalido-mide extended dosing (CRD-R) induces high rates of MRD negativity in newly diagnosed multiple myeloma (MM) patients. Proc ASH 2013;Abstract 538.

LandgrenOetal.Clinical and correlative pilot study of carfilzomib, lenalidomide, and dexamethasone followed by lenalido-mide extended dosing (CRd – R) in high risk smoldering multiple myeloma patients. Proc ASH2013;Abstract 1939.

LohrJGetal.Widespread genetic heterogeneity in multiple myeloma: Implications for targeted therapy. Cancer Cell 2014;25(1):91-101.

Martinez-LopezJetal.Prognostic value of deep sequencing approach for minimal residual disease (MRD) detection in multiple myeloma patients. Proc ASH2013;Abstract 1848.

Martinez-LopezJetal.Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma. Blood2014;123(20):3073-9.

McCarthyPLetal.Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med2012;366(19):1770-81.

Randomized phase III trial of bortezomib, lenalidomide and dexamethasone (VRd) versus carfilzomib, lenalidomide, dexameth-asone (CRd) followed by limited or indefinite lenalidomide maintenance in patients with newly diagnosed symptomatic multiple myeloma. NCT01863550

RichardsonPGetal.PANORAMA 2: Panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood 2013;122(14):2331-7.

RichardsonPGetal.Twice-weekly oral MLN9708 (ixazomib citrate), an investigational proteasome inhibitor, in combination with lenalidomide (len) and dexamethasone (dex) in patients (pts) with newly diagnosed multiple myeloma (MM): Final phase 1 results and phase 2 data. Proc ASH2013;Abstract 535.

SinghPPetal. Lenalidomide maintenance therapy in multiple myeloma: A meta-analysis of randomized trials. Proc ASH2013;Abstract 407.

SonneveldPetal.Bortezomib induction and maintenance treatment improves survival in patients with newly diagnosed multiple myeloma: Extended follow-up of the HOVON-65/GMMG-HD4 trial. Proc ASH 2013;Abstract 404.

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TempletonJEetal.Chronic bilateral thigh and knee discomfort in an 18-year-old man. Clin Orthop Relat Res 2008;466(2):507-13.

TerposEetal. International Myeloma Working Group recommendations for the treatment of multiple myeloma-related bone disease. J Clin Oncol2013;31(18):2347-57.

TreonSPetal.A prospective multicenter study of the Bruton’s tyrosine kinase inhibitor ibrutinib in patients with relapsed or refractory Waldenstrom’s macroglobulinemia. Proc ASH 2013;Abstract 251.

TreonSPetal.Carfilzomib, rituximab and dexamethasone (CaRD) is highly active and offers a neuropathy sparing approach for proteasome-inhibitor based therapy in Waldenstrom’s macroglobulinemia. Proc ASH2013;Abstract 757.