Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,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,#,Confidential-Do not distribute,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,#,Confidential-Do not distribute,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,#,Confidential-Do not distribute,单击此处编辑母版标题样式,Click to edit Master text styles,Second level,Third level,U,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,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,#,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,#,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,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,#,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,#,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,MM,首次复发的治疗策略,南方医院血液科,冯 茹,MM首次复发的治疗策略,MM,具有复发难治的特征！,M,蛋白（,g/L,）,100,50,20,有症状,难治复发,复发,治疗,平台期,/,缓解,无症状,几乎所有,MM,最终可能为复发,/,难治,MM,复发,约,27,500,新发病例（欧洲）,1,约,70,000,每年患者（欧洲）,1,约,19,000,年死亡病例（欧洲）,1,1,.,Painuly U,et al.,Clinical Medicine Insights:Oncology 2013:7 5373,.,MM具有复发难治的特征！M蛋白（g/L）1005020有症状,骨髓瘤复发时克隆的异质性,Nizar J,Bahlis.Blood.2012,120:927-928,复发时的克隆与初诊克隆一致,复发时的克隆从初诊克隆线性演化而来,复发时的克隆从原始细胞演化而来，具有新的获得性基因突变或结构重排,=,优势克隆,=,次要克隆,独特线性分支突变亚克隆,线性衍生突变亚克隆,复发,肿瘤起始细胞,主克隆,优势克隆与次要克隆诊断,治疗,骨髓瘤复发时克隆的异质性Nizar J,Bahlis.Blo,MM,每次复发间隔越来越短，,因此控制进展,(TTP),至关重要,MM,仍难以治愈，治疗最终目标是为了延长患者的生存,(OS),；,MM,常常复发，且每次复发的间隔会越来越短，因此控制进展（,TTP,）对,RRMM,至关重要；,由于,RRMM,病人基线情况复杂，耐受性是治疗得以继续的保障，因此在选择方案时需要更多平衡疗效和耐受性。,第一次复发,第二次复发,第三次复发,时间,初始治疗,二线治疗,三线治疗,四线治疗,MM每次复发间隔越来越短，MM仍难以治愈，治疗最终目标是为了,患者接受治疗获得最大缓解后发生疾病进展，,即符合以下任一项比基线值升高,25%,1,：,1),血清,M,蛋白和,/,或，,(,且升高的绝对值,5g/l),2)24h,尿,M,蛋白和,/,或，,(,且升高的绝对值,200 mg/24 hours),3),如果血清和尿中,M,蛋白无法检测，要求受累游离轻链与非受累游离轻链之间的差值,(,增加的绝对值必须达到,10mg/dl,),4),骨髓浆细胞比例，绝对值必须达到,10%,5),现存骨病变或软组织浆细胞瘤增大，或出现新的溶骨性病变或软组织浆细胞瘤,6),出现仅与浆细胞异常增殖有关的高钙血症,(11.5mg/dl),1,、,Antonio Palumbo,et al.J Clin Oncol,2,013.48.7934,.,国际骨髓瘤工作组,(IMWG),关于复发的最新定义,获得,CR,后复发,，,即符合以下任一项,1,：,1),免疫固定电泳或常规电泳检查血,/,尿,M,蛋白再次出现,2),骨髓浆细胞比例,5%,3),出现疾病进展的任何其他指征（新发浆细胞瘤、溶骨性病灶或高钙血症）,国际骨髓瘤工作组(IMWG)关于复发的最新定义,IMWG 2014,版共识增加,M,蛋白显著快速上升,亦为需要治疗的复发,，即符合以下任一项：,1)2,个月内单克隆免疫球蛋白翻倍，连续两次血清,M,蛋白升高的绝对值,1g/dL,2)2,个月内单克隆免疫球蛋白翻倍，连续两次,24,小时尿,M,蛋白升高的绝对值,500mg,国际骨髓瘤工作组,(IMWG),关于复发的定义,1,、,Antonio Palumbo,et al.J Clin Oncol,2013.48.7934,.,国际骨髓瘤工作组(IMWG)关于复发的定义1、Antonio,一线治疗是否使用新药？,存在以下情况：换药治疗,存在以下情况：,换药或再治疗,考虑移植,移植前诱导,换用新药,Adapted from:Ludwig H,et al.Oncologist.2012;17:592-606.,首次复发的治疗策略,是,否,换药还是重复初始治疗？,含来那度胺方案,含硼替佐米方案,含沙利度胺方案,研发中的新药,长期缓解,（缓解持续时间,中位,PFS,）,初始治疗没有产生相关毒性,短期缓解,（缓解持续时间,中位,PFS,）,初始治疗没有产生相关毒性,短期缓解,（缓解持续时间,中位,PFS,）,初始治疗没有产生相关毒性,短期缓解,（缓解持续时间,