资源描述
单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level, Management Strategies in Non-Hodgkins Lymphoma,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级, Management Strategies in Non-Hodgkins Lymphoma,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level, Management Strategies in Non-Hodgkins Lymphoma,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level, Management Strategies in Non-Hodgkins Lymphoma,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,弥漫大B细胞淋巴瘤治疗新进展,张翼鷟,天津医科大学附属肿瘤医院血液科,天津市肿瘤防治重点实验室,aprilzyzyahoo,概述,流行病学,基于分子,生物学,改变,的,预后评价,治疗进展,初治的DLBCL,难治复发的DLBCL,新药临床试验,概述,流行病学,弥漫大,B,细胞淋巴瘤,:31%,滤泡性淋巴瘤,:22%,边缘区淋巴瘤,:8%,套细胞淋巴瘤,:6%,小细胞淋巴瘤,7%,外周,T,细胞淋巴瘤,:7%,HL,及,NHL,的发病率,B-NHL 6632,66%,UC 378,4%,HL 854,9%,T/NK-NHL 2138,21%,病例总数：,10002,SMZL,41,1%,B-LBL,172,3%,UC,387,6%,DLBCL,NOS,3328,48%,MCL,307,5%,PCNs,221,3%,BL,107,2%,MMZL,99,1%,LPL,57,1%,DLBCL,SS,378,6%,MALTL,685,10%,FL,551,8%,CLL/SLL,424,6%,病例总数：,6638,B-NHL,亚型的发病率,DLBCL FL MALTL,MCL CLL/SLL BL SMZL NMZL,弥漫大B细胞淋巴瘤,最常见的非霍奇金淋巴瘤:31%,发病顶峰:60岁,临床表现及分子生物学特征:,高度异质性 大细胞,无淋巴滤泡结构,中位生存期:数周/月(假设不治疗),30%到 40%伴有B 病症,可能伴有结外病变(胃肠道,中枢神经系统,睾丸,皮肤),Michallet AS,et al.Blood Rev.2021;23:11-23.,2021年NCCN指南:Essential Diagnostic Assessments for DLBCL,对所有切片进行血液病理学检查(至少1个为含有肿瘤组织的石蜡块),淋巴结切检,当淋巴结难以切除或切取活检时,联合FNA和空心针活检并结合辅助检查,时免疫表型:(DLBCL typically CD20+,CD45+,CD3-),免疫组化(石蜡切片):CD20,CD3,CD4,CD10,CD45,BCL2,BCL6,Ki-67,IRF-4/MUM1,流式细胞学:CD45,CD3,CD5,CD19,CD10,CD20,kappa/lambda,NCCN Practice Guidelines in Oncology.2021.,弥漫大,B,细胞淋巴瘤的预后因素,不良预后因素影响化疗效果与生存期,年龄,60,岁,LDH,正常值,一般状态评分,2,Ann Arbor,分期,III/IV,结外受累区,1,个,*,Prognostic for patients older than 60 yrs of age only.,International NHL Prognosis Factors Project.N Engl J Med.1993;329:987-994.,Yrs,Percent Survival,Very good,Good,Poor,P,.0001,基于修正IPI评分的总生存率,1.0,0.9,0.8,0.7,0.6,0.5,0.4,0.3,0.2,0.1,0,0,1,2,3,4,5,Sehn LH,et al.Blood.2007;109:1857-1861.,与弥漫大B细胞淋巴瘤相关的分子遗传学改变,遗传学异常较常见,染色体异位:50%,DNA 失衡:高达67%,Abramson JS,et al.Blood.2005;106:1164-1174.,Yrs,OS,基因表达谱-分子水平将DLBCL分为不同的临床亚型,1.0,0.8,0.6,0.4,0.2,0,0,2,4,6,8,10,Rosenwald A,et al.,J Exp Med.2003;198:851-862.,Rosenwald A,et al.N Engl J Med.2002;346:1937-1947.,Copyright 2002 Massachusetts Medical Society.All rights reserved.,0,0.2,0.4,0.6,0.8,1.0,0,4,8,Probability of Survival,6,10,2,P,10 yrs,经过微阵列处理的相关性研究,指标:比例风险模式(FFS,OS),Winter JN,et al.ASH 2021.Abstract 87.,基于基因表达的风险评分-预测,DLBCL,临床结果,N=183,合格者,可评估案例,6 genes for R-CHOP,5 genes for CHOP(single gene overlap,LMO2,),High-vs low-gene risk scores significantly predicted E4494 clinical outcome(median follow-up:9.4 yrs),Winter JN,et al.ASH 2021.Abstract 87.,基于基因表达的风险评分-预测,DLBCL,临床结果,CHOP,R-CHOP,Winter JN,et al.ASH 2021.Abstract 87.,Probability,1.0,0.8,0.6,0.4,0.2,0,12,0,2,4,6,8,10,Yrs,FFS,P,=.003,Median,Median,1.0,0.8,0.6,0.4,0.2,0,12,0,2,4,6,8,10,Yrs,OS,P,=.001,Median,Median,1.0,0.8,0.6,0.4,0.2,0,12,0,2,4,6,8,10,Yrs,FFS,P,=.001,1.0,0.8,0.6,0.4,0.2,0,12,0,2,4,6,8,10,Yrs,OS,P,=.0015,基于基因表达的风险评分-预测,DLBCL,临床结果,High-vs low-gene risk scores significantly predicted OS,CHOP(median follow-up:7.6 yrs;,P,.0001),R-CHOP(median follow-up:2.8 yrs;,P,=.0014),基因风险评分对调整后的IPI多元分析具有预测意义,Winter JN,et al.ASH 2021.Abstract 87.,基于基因表达的风险评分-预测,DLBCL,临床结果,该预测模型也可区分一些不同来源的细胞的差异,CHOP:significant difference among nongerminal center B-cell(GCB)cases(,P,=.0002),R-CHOP:significant difference among GCB cases(,P,=.03),Molecular predictors largely independent of IPI in both CHOP,R-CHOP patients,Winter JN,et al.ASH 2021.Abstract 87.,弥漫大,B,细胞淋巴瘤的治疗进展,初治,DLBCL,CHOP Rituximab in DLBCL:GELA LNH-98.5 Phase III Study,Primary endpoint:EFS,Secondary endpoints:OS,RR,R-CHOPevery 3 wks for 8 cycles(n=202),CHOPevery 3 wks for 8 cycles(n=197),Untreated elderly patients with stage II-IV DLBCL,(N=399),Stratified by risk factors(0-1 vs 2-3),Assessment,Coiffier B,et al.N Engl J Med.2002;346:235-242.Feugier P,et al.J Clin Oncol.2005;23:4117-4126.,Maint.Ritux.After R-CHOP or CHOP in Older DLBCL(E4494/C9793 Ph III Study),Primary endpoint:FFS,Morrison VA,et al.ASCO 2007.Abstract 8011.Habermann TM,et al.J Clin Oncol.2006;24:3121-3127.,Untreated patients with CD20+DLBCL,60 yrs of age or older,PS 0-3,(N=632),R-CHOP x 6-8 cycles(n=318),CHOP x 6-8 cycles(n=314),Stratified by IPI score(0-1 vs 2-4),Responders,(n=415),Maintenance Rituximabq6mos x 2 yrs,starting 4 wks after last cycle(n=207),Observation(n=208),Stratified by IPI score,CR/PR,induction,Cunningham D,et al.ASCO 2021.Abstract 8506.,Newly diagnosed CD20+DLBCL,patients,(N=1080),R-CHOP-14 x 6 cycles+,Rituximab x 8 cycles+,Lenograstim on Days 4-12,(n=540),R-CHOP-21 x 8 cycles+,Rituximab x 8 cycles,(n=540),Stratified by IPI score and age,R-CHOP-14 vs R-CHOP-21 in Newly Diagnosed DLBCL(Phase III Study),Primary endpoint:OS,Secondary endpoint:FFS,toxicity,response rates,Cunningham D,et al.ASCO
展开阅读全文