多发性骨髓瘤研究进展和治疗选择课件

New Developments and Treatment Options for Multiple Myeloma Robert Z. Orlowski, MD, PhD Mary Elizabeth Thomas Associate Professor of Medicine, Division of Hematology/Oncology Associate Professor, Department of Pharmacology 多发性骨髓瘤 研究进展和治疗选择 Robert Z. Orlowski, MD, PhD Mary Elizabeth Thomas Associate Professor of Medicine, Division of Hematology/Oncology Associate Professor, Department of Pharmacology Outline Diagnosis, staging and risk identification Initial therapy in newly diagnosed myeloma patients Novel options for patients in the relapsed and/or refractory setting Representative case presentations of current myeloma treatment algorithms 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 Diagnostic Criteria Major Criteria 1. Plasmacytoma on tissue biopsy 2. Bone marrow plasmacytosis 30% 3. Monoclonal serum protein 3.5 g/dL IgG 2.0 g/dL IgA 1.0 g/24 hrs k or l light chain in urine Minor Criteria A. Bone marrow plasmacytosis 10-30% B. Smaller monoclonal spike than in major criterion #2 C. Lytic bony lesions D. Depressed normal Igs IgM 30% 3. 过量血清M蛋白 3.5 g/dL IgG 2.0 g/dL IgA 尿中k 或 l轻链 1.0 g/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 2.75 mmol/L, or 0.25 mmol/L above upper limit of normal) Renal insufficiency (creatinine 173 mmol/L) Other (hyperviscosity, amyloidosis, recurrent bacterial infections 2 episodes in 12 months) Kyle, RA et al. 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 (2.75 mmol/L, 或高于正常值上限 0.25 mmol/L) 肾功能不全 (肌酐 173 mmol/L) 其他 (高粘血症, 淀粉样变, 反复细菌感染 2 次/12个月) Kyle, RA et al. Br. J. Haematol. 121:749, 2003. Durie-Salmon Staging System Several factors are included in the staging1 Hemoglobin Renal function Serum calcium M-protein production Bony lesions and/or presence of a plasmacytoma Drawbacks Many factors make it cumbersome to apply Does not use new, powerful prognostic tools International Myeloma Working Group studied 11,171 patients2 Multivariate analysis found only b2-microglobulin and albumin as prognostic factors 1Durie, BGM and Salmon, SE. Cancer 36:842, 1975. 2Greipp, PR et al. Blood 102:190a, Abstract 664, 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, BGM and Salmon, SE. Cancer 36:842, 1975. 2Greipp, PR et al. Blood 102:190a, Abstract 664, 2003. International Staging System Greipp, PR et al. J. Clin. Oncol. 23:3412, 2005. Stageb2MAlbuminNOS I1 prior treatment Len/dex had a better overall RR & CR rate 欧洲结果 351 名患者随机入 组 len/dex 176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 Time to Progression Time to Progression (months) Proportion of Patients 2.557.51012.51517.52022.5 0 0.2 0.4 0.6 0.8 1.0 Len/Dex 13.3 mos. Dex alone 5.1 mos. P 200 100- 200 70- 100 50- 70 20- 50 75 X 103/mL to 50 10 200 100- 200 70- 100 50- 70 20- 50 75 X 103/mL 至 50 10 200k, only 13% developed grade 3/4 thrombocytopenia 200-100k: 56% (1% grade 4) 100-70k: 90% (all grade 3) All pts developed a predictable 60% reduction Recovery occurs during the rest period VELCADE doesnt kill megakaryocytes Lonial, S et al. Blood 106:3777-3784, 2006. 血小板减少概况 血小板减少 如果基线 200k, 只有13% 出现3/4级血小板 减少 200-100k: 56% (1% 4级) 100-70k: 90% (均为3级) 所有病人出现可预测的60% 的降低 在休息期恢复 万珂 不杀伤巨核细胞 Lonial, S et al. Blood 106:3777-3784, 2006. Kinetics of Thrombocytopenia Platelet nadir is 40% of baseline Mean Platelet Count (109/L) Time Lonial, S et al. Blood 106:3777-3784, 2006. 血小板减少的变化 血小板最低值 为 基线的40% Mean Platelet Count (109/L) Time Lonial, S et al. Blood 106:3777-3784, 2006. Incidence of Platelet Support Median baseline platelets for patients not requiring a transfusion = 182 x 103/mL Median baseline platelets for patients requiring a transfusion= 65.5 x 103/mL Rare instances of gastrointestinal and intracerebral hemorrhages Lonial, S et al. Blood 106:3777-3784, 2006. 血小板减少的发生率 中位基线血小板（不需输 注者） = 182 x 103/mL 中位基线血小板（需要输 注者） = 65.5 x 103/mL 消化道及颅内出血罕见 Lonial, S et al. Blood 106:3777-3784, 2006. Thrombocytopenia and Response (CR + PR) P = .054 In Phase II, there was a trend for patients with responsive disease to have a lower incidence of thrombocytopenia Lonial, S et al. Blood 106:3777-3784, 2006. 血小板减少与疗效 (CR + PR) P = .054 在II期临床中, 观察 到缓解的病人有血 小板减少发生率低 的趋势 Lonial, S et al. Blood 106:3777-3784, 2006. Recommendation for Part II Since thrombocytopenia may suggest a lower likelihood of response, the patients disease status needs to be re-evaluated If this shows a continuing response to therapy, or stable disease, and because the patient has grade 3 thrombocytopenia . THEN I would recommend continuing on schedule, and adding platelet support if needed 对第 II 部分建议 由于血小板减少可能提示缓解不佳，需重 新评价病人的疾病状况 如果显示对治疗有持续的缓解或稳定，而 病人有3级血小板减少. 所以 我推荐按计划治疗，如果需要给予血小板 输注支持 Research Personnel Clinical E. Claire Dees Peter M. Voorhees Thomas E. Stinchcombe Reynaldo A. Garcia Melissa D. Hall Mary Jo Lehman Susan Natoli Stephanie Stahl Laboratory George W. Small Deborah J. Kuhn Peter M. Voorhees Yue Y. Shi Sivagurunathan Somasundaram 参与研究人员 临床 E. Claire Dees Peter M. Voorhees Thomas E.