多发性骨髓瘤研究进展和治疗选择

NewDevelopmentsandTreatmentOptionsforMultipleMyeloma RobertZ Orlowski MD PhDMaryElizabethThomasAssociateProfessorofMedicine DivisionofHematology OncologyAssociateProfessor DepartmentofPharmacology 多发性骨髓瘤研究进展和治疗选择 RobertZ Orlowski MD PhDMaryElizabethThomasAssociateProfessorofMedicine DivisionofHematology OncologyAssociateProfessor DepartmentofPharmacology Outline Diagnosis stagingandriskidentificationInitialtherapyinnewlydiagnosedmyelomapatientsNoveloptionsforpatientsintherelapsedand orrefractorysettingRepresentativecasepresentationsofcurrentmyelomatreatmentalgorithms 内容大纲 诊断 分期 及风险评估初治骨髓瘤病人的初始治疗复发和 或难治性病人的新选择当前骨髓瘤治疗法则的代表性病例分析 DiagnosticCriteria MajorCriteria1 Plasmacytomaontissuebiopsy2 Bonemarrowplasmacytosis 30 3 Monoclonalserumprotein 3 5g dLIgG2 0g dLIgA1 0g 24hrskorllightchaininurine MinorCriteriaA Bonemarrowplasmacytosis10 30 B Smallermonoclonalspikethaninmajorcriterion 2C LyticbonylesionsD DepressednormalIgsIgM 500mg dLIgA 1g dLIgG 6g dL 诊断标准 主要标准1 组织活检证实有浆细胞瘤2 骨髓浆细胞增多 30 3 过量血清M蛋白 3 5g dLIgG2 0g dLIgA尿中k或l轻链1 0g 24小时 次要标准A 骨髓浆细胞增多10 30 B M蛋白未达主要标准的第3项C 溶骨性病变D 正常Igs降低IgM 500mg dLIgA 1g dLIgG 6g dL ArrivingattheDiagnosis TwomajorcriteriaOnemajor oneminorcriterion1 B 1 C 1 D2 B 2 C 2 D3 A 3 C 3 DThreeminorcriteriathatincludeAandBA B C A B D 1Clusterofplasmacellsinthebonemarrow Bataille RandHarousseau JL N Engl J Med 336 1657 1997 1 确诊条件 2个主要标准1个主要 1个次要标准1 B 1 C 1 D2 B 2 C 2 D3 A 3 C 3 D包含A及B的三个次要标准A B C A B D 1Clusterofplasmacellsinthebonemarrow Bataille RandHarousseau JL N Engl J Med 336 1657 1997 1 ProblemswithThisMethod CriteriaarecumbersomeDifficulttouseforpatientsandphysiciansTheboundariesarearbitrary31 marrowplasmacytosisisamajorcriterionwhile29 isn t butarethesereallydifferent Somepatientsmay fallthroughthecracks Apatientwithmultiplepainfullyticlesionsmaynotmeetcriteria butneedssystemictherapy40 ofsymptomaticpatientshaveanM proteinof 30g L and5 have 10 marrowinvolvement 这项标准存在的问题 判定标准烦琐不方便病人及医生使用界线设定独断31 骨髓浆细胞增多为主要标准而29 则不是 但两者是否存在差异 部分病人可能处于 夹缝状态 某些有多发性痛性溶骨病变的病人可能没有达到判定标准 但需要系统性治疗40 有症状的病人表现为M蛋白 30g L 并且5 表现为 10 骨髓侵润 MGUS InternationalMyelomaWorkingGroupcriteriaM proteininserum 3 0g dLClonalbonemarrowplasmacytosisof 10 andalowlevelofplasmacellinfiltrationinamarrowbiopsy ifthiswasdoneNootherB cellproliferativedisorderNoendorgandamage includingbonelesions Kyle RAetal Br J Haematol 121 749 2003 MGUS 国际骨髓瘤工作组判定标准血清M蛋白 3 0g dL骨髓浆细胞增多 10 并且如进行骨髓活检 可见浆细胞侵润程度低无其它B细胞增殖异常无终末器官损伤 包括骨病变 Kyle RAetal Br J Haematol 121 749 2003 AsymptomaticMultipleMyeloma Previously smo u lderingmyeloma SerumM protein 3 0g dLand orClonalmarrowplasmacytosis 10 Norelatedorganortissueimpairment noendorgandamage includingbonelesions orsymptoms Kyle RAetal Br J Haematol 121 749 2003 无症状多发性骨髓瘤 以前的 冒烟型骨髓瘤 血清M蛋白 3 0g dL和 或骨髓浆细胞增多 10 无相关器官或组织损伤 无终末器官损伤 包括骨病变 或症状 Kyle RAetal Br J Haematol 121 749 2003 SymptomaticMultipleMyeloma Presenceofaserumand orurineM proteinClonalmarrowplasmacytosisorplasmacytoma10 isgenerallyacceptedRelatedorganortissueimpairmentAnemia 2 75mmol L or 0 25mmol Laboveupperlimitofnormal Renalinsufficiency creatinine 173mmol L Other hyperviscosity amyloidosis recurrentbacterialinfections 2episodesin12months Kyle RAetal Br J Haematol 121 749 2003 有症状多发性骨髓瘤 血清和 或尿中有M蛋白骨髓浆细胞增多或浆细胞瘤通常以10 为标准相关器官或组织损伤贫血 2 75mmol L 或高于正常值上限 0 25mmol L 肾功能不全 肌酐 173mmol L 其他 高粘血症 淀粉样变 反复细菌感染 2次 12个月 Kyle RAetal Br J Haematol 121 749 2003 Durie SalmonStagingSystem Severalfactorsareincludedinthestaging1HemoglobinRenalfunctionSerumcalciumM proteinproductionBonylesionsand orpresenceofaplasmacytoma DrawbacksManyfactorsmakeitcumbersometoapplyDoesnotusenew powerfulprognostictoolsInternationalMyelomaWorkingGroupstudied11 171patients2Multivariateanalysisfoundonlyb2 microglobulinandalbuminasprognosticfactors 1Durie BGMandSalmon SE Cancer36 842 1975 2Greipp PRetal Blood102 190a Abstract664 2003 Durie Salmon分期系统 本分期系统中包括下列指标1血红蛋白肾功能血清钙M蛋白骨病变和 或有浆细胞瘤 缺点指标太多不方便使用没有包括新的 有力的预后工具国际骨髓瘤工作组研究了11 171例病人2多变量分析发现 只有b2微球蛋白及白蛋白是预后因子 1Durie BGMandSalmon SE Cancer36 842 1975 2Greipp PRetal Blood102 190a Abstract664 2003 InternationalStagingSystem Greipp PRetal J Clin Oncol 23 3412 2005 国际分期系统 ISS Greipp PRetal J Clin Oncol 23 3412 2005 1 Greipp PRetal J Clin Oncol 23 3412 2005 ISSandPrognosis Significantsurvivaldifferencesforthreestages P 0 0001 BetteroutcomepredictorthanthepriorDurie SalmonmethodStilldoesnotincorporatecytogenetics 1 Greipp PRetal J Clin Oncol 23 3412 2005 ISS与预后的关系 三期间有显著的生存差异 P 0 0001 与Durie Salmon分期相比 有更好的预测结果但仍未包括细胞遗传学指标 CytogeneticFactors Del13 Deletionofchromosome13wasthesinglemostpowerfuladverseprognosticfactorforalltimestoeventsinpatientsreferredforhigh dosetherapyOS65 1 9 8vs26 7 4 1months Facon Tetal Blood97 1566 2001 细胞遗传学指标 13号染色体缺失 在接受高剂量化疗的病人中 13号染色体缺失是单一最有效的负面预后因子 影响所有的 至事件发生时间 指标总生存65 1 9 8vs26 7 4 1个月 Facon Tetal Blood97 1566 2001 BortezomibandDel13 APEXrandomizedpatientstobortezomibordexamethasone11 74 15 onthebortezomibarmand13 94 14 onthedexarmhadmetaphasedel13Del13wasassociatedwithpoorsurvivalondexarmcomparedwithcontrolsDel13wasnotassociatedwithaninferiorsurvivalonthebortezomibarm Jagannath Setal ASCOAbstract6501 2005 万珂与13号染色体缺失 APEX将病人随机分入万珂组或地塞米松组万珂组11 74 15 地塞米松组13 94 14 有分裂中期13号染色体缺失地塞米松组 13号染色体缺失与更差的生存期相关 与对照相比 万珂组 13号染色体缺失与更差的生存期无关 Jagannath Setal ASCOAbstract6501 2005 Conclusions StagingandprognosisismostaccuratelydeterminedusingtheISSNewprognosticfactorsareemergingthatmayhelprefinethisfurtherCytogeneticandFISHstudiescanprovideadditionalprognosticinformation andintheverynearfuturemayguidetherapeuticdecisions 结论 用ISS能更好地确定分期及预后新的预后因子正在显现 未来可对分期预后系统有进一步的改进细胞遗传学及FISH研究能提供更多的预后信息 在不久的将来可能会为治疗方法的确定提供指导 Outline Diagnosis stagingandriskidentificationInitialtherapyinnewlydiagnosedmyelomapatientsPatientswithtransplantasanoptionNoveloptionsforpatientsintherelapsedand orrefractorysettingRepresentativecasepresentationsofcurrentmyelomatreatmentalgorithms 内容大纲 诊断 分期 及风险评估初治骨髓瘤病人的初始治疗能进行移植的病人复发和 或难治性病人的新选择当前骨髓瘤治疗法则的代表性病例分析 Thalidomide Dexamethasone Thal dexsuperiortodex p 0 002 1Mediantimetoresponseforbothwas1 1mosProgression3 vs 5 Progressionfreesurvival25 3vs 17 3monthsStemcellharvestsweresuccessful 1Bestresponsewasevaluatedwithin4cycles 200mgpoqd PRwas 50 serum urineM proteinreduction or 90 urineM reductionifonlyurinewasinvolved RajkumarSVetal J Clin Oncol 24 431 2006 沙立度胺 地塞米松 Thal dex优于dex p 0 002 1中位至缓解时间均为1 1个月进展3 vs 5 无进展生存25 3vs 17 3个月可成功采集干细胞 1Bestresponsewasevaluatedwithin4cycles 200mgpoqd PRwas 50 serum urineM proteinreduction or 90 urineM reductionifonlyurinewasinvolved RajkumarSVetal J Clin Oncol 24 431 2006 DVdvs VAdasInitialTherapy DVd D 40mg m2d1 V 1 4mg m2withmax of2mgd1 d 40mgd1 4 Rifkin RMetal ASCOAbstract6509 2004 DVdalsohadlessneutropenia alopecia andchangesintheLVEF butatthecostofHFS PPE DVdvs VAd作为初始治疗 DVd D 40mg m2d1 V 1 4mg m2withmax of2mgd1 d 40mgd1 4 Rifkin RMetal ASCOAbstract6509 2004 DVd组中性粒细胞减少 脱发 LVEF改变发生少 但HFS PPE较多 ShouldWePushHarderforaCR 668ptsundergoingTotalTherapy2StringentCRassociatedwithanimproved4 yearOSandEFSHowever nodifferenceinoutcomebetweenPRand PRpatients whohadvirtuallysuperimposablesurvivalcurves Tricot Getal ASHAbstract936 2004 我们是否应更努力去取得CR 668例病人接受TotalTherapy2方案治疗以严格的CR判定标准 取得了更好的4年总生存率及无事件生存率但是 PR与 PR间结果无差异 其生存曲线令人意外 Tricot Getal ASHAbstract936 2004 CombinationTherapywithLenalidomidePlusDexamethasone Rev Dex forNewlyDiagnosedMyeloma S VincentRajkumar SuzanneHayman MarthaQ Lacy AngelaDispenzieri SusanM Geyer BrianKabat StevenR Zeldenrust ShajiKumar PhilipR Greipp RafaelFonseca JohnA Lust StephenJ Russell RobertA Kyle ThomasE Witzig MorieA GertzDivisionofHematology MayoClinic Rochester MN USA DivisionofBiostatistics MayoClinic Rochester MN USA DivisionofHematology Oncology MayoClinic Scottsdale AZ USA Abstract781 Lenalidomide联合地塞米松 Rev Dex 治疗新诊断的骨髓瘤 S VincentRajkumar SuzanneHayman MarthaQ Lacy AngelaDispenzieri SusanM Geyer BrianKabat StevenR Zeldenrust ShajiKumar PhilipR Greipp RafaelFonseca JohnA Lust StephenJ Russell RobertA Kyle ThomasE Witzig MorieA GertzDivisionofHematology MayoClinic Rochester MN USA DivisionofBiostatistics MayoClinic Rochester MN USA DivisionofHematology Oncology MayoClinic Scottsdale AZ USA 摘要781 StudyDesign Studyof Rev dex regimenin34previouslyuntreatedpatientsPhaseII prospectivetrialdesignLenalidomide 25mgpodays1 21q28Dexamethasone40mgpodays1 4 9 12 and17 20Aspirin 80or325mg dailyforDVTprophylaxis Rajkumar SVetal Blood106 4050 2005 研究设计 34例初治患者接受 Rev dex 方案治疗临床II期 前瞻性研究设计Lenalidomide 25mgpodays1 21q28地塞米松40mgpodays1 4 9 12 17 20阿司匹林 每日80or325mg 预防深部静脉血栓形成 DVT Rajkumar SVetal Blood106 4050 2005 Responses Responseratewas91 31 34 definedaspatientswith 50 serumM proteinreductionand 90 urineM proteinCRratewas6 2 34 Another32 11 34 achievedvgPR nCR53 18 34 hadaPRAmongpatientswhodidnotachievearesponse 2hadMRand1hadSDStemcellscouldbecollectedsuccessfully 疗效 缓解率91 31 34 定义为患者血浆M 蛋白减少 50 及尿M 蛋白减少 90 完全缓解率 CR6 2 34 另外32 11 34 获得vgPR nCR53 18 34 部分缓解未缓解者中 2例MR 1例SD可成功采集干细胞 Toxicities 毒性反应 PADRegimen Day Bortezomib1 3mg m2 1 4 8 15 18 Cycle1 11 21 Dex40mg Dox0 4 5 or9mg m2 Bortezomib1 3mg m2 1 4 8 15 18 Cycles2 4 11 21 Dex40mg Dox0 4 5 or9mg m2 NewlydiagnosedptsbeforestemcelltransplantEvaluateresponserates toxicity andstemcellharvestandsubsequenttransplantation Oakervee HEetal Br J Haematol 129 755 2005 PAD方案 天 万珂1 3mg m2 1 4 8 15 18 第1周期 11 21 地塞米松40mg 阿霉素0 4 5 or9mg m2 万珂1 3mg m2 1 4 8 15 18 第2 4周期 11 21 地塞米松40mg 阿霉素0 4 5 or9mg m2 干细胞移植前的初治患者评价疗效 毒性反应 干细胞采集 及后续移植治疗 Oakervee HEetal Br J Haematol 129 755 2005 OutcomesData 95 CR PRrateafterPADinductiontherapyalone 20 21 CR near CRrate24 20 21patientsweremobilizedsuccessfully18 20transplantedCR near CRroseto57 MyelomaProtein g L 0 10 20 30 40 50 60 70 80 90 Pre Rx 1 2 3 4 TreatmentCycle Oakervee HEetal Br J Haematol 129 755 2005 疗效结果 单用PAD诱导治疗后 CR PR95 20 21 CR nCR24 20 21例干细胞动员成功18 20进行了移植CR nCR提高到57 M蛋白 g L 0 10 20 30 40 50 60 70 80 90 Pre Rx 1 2 3 4 治疗周期 Oakervee HEetal Br J Haematol 129 755 2005 Toxicities DiscontinuationsoccurredduetoposturalhypotensionandneuropathyDrug relatedSAEsincludedposturalhypotension shingles nausea vomiting andperipheralneuropathySensoryneuropathyin48 5 grade3 Painfulneuropathyin48 grade3in5 Allimprovedafterthecompletionoftherapy Oakervee HEetal Br J Haematol 129 755 2005 毒性反应 因体位性低血压及神经毒性出现停药药物相关的SAEs包括体位性低血压 带状疱疹 恶心 呕吐 及周围神经病变感觉神经病变48 5 为3级 神经病变伴疼痛48 3级为5 所以病例在治疗结束后有改善 Oakervee HEetal Br J Haematol 129 755 2005 ReducedDosePADCombinationTherapy PS 341 Bortezomib AdriamycinandDexamethasone forPreviouslyUntreatedPatientswithMultipleMyelomaRakeshPopat HeatherE Oakervee NicolaCurry NicolaFoot CurlyMorris MaryDrake SamirAgrawal PatriciaSmith DavidSchenkein Dixie LeeEsseltine JamieD CavenaghHaematology St Bartholomew sHospital London UnitedKingdom Haematology BelfastCityHospital Belfast UnitedKingdom MillenniumPharmaceuticals Cambridge MA USA Abstract2554 减量PAD联合方案 PS 341 硼替佐米 阿霉素和地塞米松 治疗初治的多发性骨髓瘤RakeshPopat HeatherE Oakervee NicolaCurry NicolaFoot CurlyMorris MaryDrake SamirAgrawal PatriciaSmith DavidSchenkein Dixie LeeEsseltine JamieD CavenaghHaematology St Bartholomew sHospital London UnitedKingdom Haematology BelfastCityHospital Belfast UnitedKingdom MillenniumPharmaceuticals Cambridge MA USA Abstract2554 Toxicities 9 sensoryand9 painfulneuropathy allgrade1 21discon tinuationMRSA 毒性反应 9 感觉性 9 痛性周围神经病变 所有均为1 2级1退出治疗MRSA 甲氧西林耐药金黄色葡萄球菌 Responses ExcellentresponserateStemcellsmobilizationnotimpactedbyPADImprovedtoxicityprowithhigherdosePAD 疗效 出色的缓解率PAD不影响干细胞动员与高剂量PAD方案相比 毒性反应降低 Conclusions Newinductionregimensareemergingthathavetheabilitytoinduceoverallresponseratesof90 ormore withmoreCRsPatientsareabletohavestemcellscollectedandmoveontotransplantationsafelyAdditionalstudieswillbeneededtoidentifytheoptimalregimen s 结论 新的诱导方案正在出现 能达到90 以上的总缓解率 其中有更多的CRs能进行干细胞采集 并安全地进行移植需要进行更多的研究以发现最佳方案 Outline Diagnosis stagingandriskidentificationInitialtherapyinnewlydiagnosedmyelomapatientsPatientswithouttransplantasanoptionNoveloptionsforpatientsintherelapsedand orrefractorysettingRepresentativecasepresentationsofcurrentmyelomatreatmentalgorithms 内容大纲 诊断 分期 及风险评估初治骨髓瘤病人的初始治疗不能进行移植的病人复发和 或难治性病人的新选择当前骨髓瘤治疗法则的代表性病例分析 APhaseI IINational Multi Center Open LabelStudyofBortezomibPlusMelphalanandPrednisone V MP inElderlyUntreatedMultipleMyeloma MM Patients M V Mateos M Hern ndez J D azMediavilla L Palomera M J Moro J Hern ndez J J Lahuerta J DelaRubia M J Terol A Sureda J Bargay F Arriba A Alegre P Rivas J Garc a Lara a J M Ribera D Carrera J Blad F Pr sper D L Esseltine H vandeVelde D Schenkein J F SanMiguelGrupoEspa oldeMM GEM PETHEMA Spain MilenniumPharmaceuticals INC Cambridge MA USA JohnsonandJohnsonPharmaceuticalResearchandDevelopment Beerse Belgium Abstract786 万珂联合美法兰 强的松 V MP 用于老年初治的多发性骨髓瘤患者 MM 的I II期全国 多中心 开放性的研究 M V Mateos M Hern ndez J D azMediavilla L Palomera M J Moro J Hern ndez J J Lahuerta J DelaRubia M J Terol A Sureda J Bargay F Arriba A Alegre P Rivas J Garc a Lara a J M Ribera D Carrera J Blad F Pr sper D L Esseltine H vandeVelde D Schenkein J F SanMiguelGrupoEspa oldeMM GEM PETHEMA Spain MilenniumPharmaceuticals INC Cambridge MA USA JohnsonandJohnsonPharmaceuticalResearchandDevelopment Beerse Belgium Abstract786 StudyDesign PhaseI IIstudyPatientswithmyeloma 65yearsofageFourcyclesof6weekseachMPdays1 4Bortezomibdays1 4 8 11 22 25 29 32Fivecyclesof5weekseachMPdays1 4Bortezomibdays1 8 15 22 研究设计 临床I II期研究 65岁骨髓瘤病人每周期6周 共4个周期MP第1 4天万珂第1 4 8 11 22 25 29 32天每周期5周 共5个周期MP第1 4天万珂第1 8 15 22天 Toxicities EventscomparabletoothermyelomaregimensEvent freesurvival85 6deathsBortezomibdosereductionsin35 Neuropathy 毒性反应 与其他骨髓瘤方案相似无事件生存率85 6例死亡35 的患者降低了万珂的剂量神经病变 Responses 86 ofpatientsrespondedHighproportionofCR IFX Responsenotinfluencedbydel13orIgHPhaseIIItrialplanned 疗效 缓解率86 CR IFX 比例高疗效不受del13或IgH的影响计划进行临床III期研究 MajorSuperiorityofMelphalan Prednisone MP Thalidomide THAL overMPandAutologousStemCellTransplantationintheTreatmentofNewlyDiagnosedElderlyPatientswithMultipleMyeloma ThierryFacon J Y Mary C Hulin L Benboubker M Attal M Renaud J L Harousseau B Pegourie G Guillerm C Chaleteix M Dib L Voillat H Maisonneuve J Troncy V Dorvaux M Monconduit C Martin P Casassus J Jaubert H Jardel B Kolb F BautersCHU LILLE OnBehalfoftheIntergroupeFrancophoneduMyelome France Abstract780 美法兰 强的松 MP 沙利度胺 THAL 治疗初治的高年多发性骨髓瘤患者优于美法兰 强的松 MP 和自体干细胞移植 ThierryFacon J Y Mary C Hulin L Benboubker M Attal M Renaud J L Harousseau B Pegourie G Guillerm C Chaleteix M Dib L Voillat H Maisonneuve J Troncy V Dorvaux M Monconduit C Martin P Casassus J Jaubert H Jardel B Kolb F BautersCHU LILLE OnBehalfoftheIntergroupeFrancophoneduMyelome France Abstract780 StudyDesign 1Clodronatewasgiventoallpatients StandardMP112coursesat6 weekintervalsn 191 MP T1MPasabove Thalupto400mgqdn 124 Mel100mg m2x21VADx2 Cy3g m2 G CSFn 121 Untreated stageI IIIpatientsage65 75 N 436 研究设计 1Clodronatewasgiventoallpatients 标准的MP112疗程 6周间隔n 191 MP T1MP同上 沙利度胺 至400mgqdn 124 Mel100mg m2x21VADx2 Cy3g m2 G CSFn 121 初治 临床I III期研究 年龄65 75岁 N 436 AResponseEdgeforMPT DVT13 inMPT vs 5and6 5 36 onMPThadPN 1Only63 ofpatientsunderwentthesecondtransplant MPT的疗效 MPT组DVT发生率13 5 6 5 36 MPT出现PN 1仅63 的患者接受第2次移植 MajorBenefitsinOSandPFS LongermedianoverallsurvivalwithMPTMPTvs MP NR 56vs 30 3mos 5 8P 0 0008MPTvs Mel100 NR 56vs38 6 3 0P 0 014LongermedianprogressionfreesurvivalMPTvs MP 29 5 3 6vs 17 2mos 1 5MPTvs Mel100 29 5 3 6vs 19 0mos 1 3 OS PFS的临床获益 MPT总体生存时间更长MPTvs MP NR 56vs 30 3月 5 8P 0 0008MPTvs Mel100 NR 56vs38 6 3 0P 0 014无进展生存时间更长MPTvs MP 29 5 3 6vs 17 2月 1 5MPTvs Mel100 29 5 3 6vs 19 0月 1 3 Toxicities 30 onMPTalsohadneuropathyDeathduetoinfectionssimilar 2 2 4 毒性反应 MPT组30 出现神经病变由于感染引起的死亡相似 2 2 4 Conclusions MPmaynolongerbethestandardofcareforallolderpatientswithmultiplemyelomaMPVandMPThavehigheroverallandcompleteresponseratesOtherregimens ThaDD arealsoeffectiveMPThasasurvivaladvantageoverMPMPRmaybebettertoleratedthanMPTAdditionalstudiesareneeded 结论 MP方案可能不再是高龄骨髓瘤病人的标准治疗MPV MPT可取得更高的总缓解率和完全缓解率其他方案 ThaDD 也显示疗效MPT与MP相比显示了生存优势需要进行进一步的临床研究 Outline Diagnosis stagingandriskidentificationInitialtherapyinnewlydiagnosedmyelomapatientsNoveloptionsforpatientsintherelapsedand orrefractorysettingRepresentativecasepresentationsofcurrentmyelomatreatmentalgorithms 内容大纲 诊断 分期 及风险评估初治骨髓瘤病人的初始治疗复发和 或难治性病人的新选择当前骨髓瘤治疗法则的代表性病例分析 StudyofLenalidomidePlusDexamethasoneVersusDexamethasoneAloneinRelapsedorRefractoryMultipleMyeloma MM ResultsofaPhase3Study MM 010 MeletiosA Dimopoulos AndrewSpencer MichaelAttal MilesPrince Jean LucHarousseau AnnaDmoszynska ZhinuanYu MartaOlesnyckyj JeromeZeldisRobertKnightUniversityGeneralAlexandrasHospital Athens Greece TheAlfredHospital Prahran Victoria Australia HopitalPurpan Toulouse France DepartmentofHematologyCelgeneCorporation Summit NJ USA Abstract6 复发性或难治性多发性骨髓瘤Lenalidomide联合地塞米松与地塞米松单药治疗的对比研究 临床III期研究结果 MM 010 MeletiosA Dimopoulos AndrewSpencer MichaelAttal MilesPrince Jean LucHarousseau AnnaDmoszynska ZhinuanYu MartaOlesnyckyj JeromeZeldisRobertKnightUniversityGeneralAlexandrasHospital Athens Greece TheAlfredHospital Prahran Victoria Australia HopitalPurpan Toulouse France DepartmentofHematologyCelgeneCorporation Summit NJ USA Abstract6 PhaseIIIStudyDesign RANDOMIZATION Placebo4 Dexamethasone2 Lenalidomide1 Dexamethasone2orPlacebo3 1Len 25mgpoqdondays1 21every28days 2Dex40mgpoqdondays1 4 9 12 and17 20every28days 3Placeboqdondays21 28ofeach28daycycle 4Placeboqdondays1 28every28days x4cycles laterDexonlydays1 4 临床III期研究的设计 随机化 安慰剂4 地塞米松2 Lenalidomide1 地塞米松2或安慰剂3 1Len 25mgpoqdondays1 21every28days 2Dex40mgpoqdondays1 4 9 12 and17 20every28days 3Placeboqdondays21 28ofeach28daycycle 4Placeboqdondays1 28every28days x4周期 随后接受Dex 第1 4天 EuropeanResults 351ptsrandomized176forlen dex175fordex placeboRelapsedorrefractorywith 1priortreatmentLen dexhadabetteroverallRR CRrate 欧洲结果 351名患者随机入组len dex176例dex 安慰剂175例复发或难治 之前的治疗 1次Len dex总RR CR率更高 TimetoProgression TimetoProgression months ProportionofPatients 2 5 5 7 5 10 12 5 15 17 5 20 22 5 0 0 2 0 4 0 6 0 8 1 0 Len Dex13 3mos Dexalone5 1mos P 0 000001 009 009 进展时间 疾病进展时间 月 患者百分数 2 5 5 7 5 10 12 5 15 17 5 20 22 5 0 0 2 0 4 0 6 0 8 1 0 Len Dex13 3月 Dex单药5 1月 P 0 000001 009 009 Toxicities L