Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * * Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * MM 导致的肾功能不全、染色体异常、高危、骨病明显、继发浆白、继发髓外浆细胞瘤、原发耐药、淀粉样变性、合并其他疾病（心功能不全、肺感染、肝功能不全、黄疸、糖尿病、高血压）、副作用预防和处理。耐药机制、联合用药。。。Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * * 结论在这个最大型的以MP 为基础的III 期研究中，VMP 显著延长了患者的生存时间，并在所有的疗效终点体现了显著优势在多个预定义的测量指标上表现出的疗效一致。迅速而持久的CR 率TTP 和TNT/TFI 时间显著延长VMP 在所有预后分组，包括不良预后组，疗效保持一致性的。VMP 耐受良好本研究的结果证明：这些结果使VMP 基于高水平证据成为不适合移植的MM 患者的新标准治疗1 1. Anderson et al. Leukemia 2008;22:231-9. 报告小结大力推广新药联合序贯移植的广泛应用，将使我们离“治愈”的目标越来越接近一线治疗的目标是：在患者耐受的情况下，早期获得CR，并提高疗效维持时间；同时改善症状，提高生活质量新药联合序贯移植是年轻患者的最佳治疗；新药联合化疗是年老患者的最佳治疗谢谢！Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * 1、目的：生存时间和质量。长生存影响因素。目标：1、在可耐受的情况下，尽早获得CR；－早期CR 的意义；2、缓解症状，提高生活质量。2、很年轻- 序贯移植TT1~3；新药的应用；自体＋异基因。3、年老：部分也可移植，PAD+ASCT+LD ；其他VMP/VMPT/MPT/ VRD 等。4、其他：MM 导致的肾功能不全、染色体异常、高危、骨病明显、继发浆白、继发髓外浆细胞瘤、原发耐药、淀粉样变性、合并其他疾病（心功能不全、肺感染、肝功能不全、黄疸、糖尿病、高血压）、副作用预防和处理。耐药机制、联合用药。。。Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * 1、目的：生存时间和质量。长生存影响因素。目标：1、在可耐受的情况下，尽早获得CR；－早期CR 的意义；2、缓解症状，提高生活质量。2、很年轻- 序贯移植TT1~3；新药的应用；自体＋异基因。3、年老：部分也可移植，PAD+ASCT+LD ；其他VMP/VMPT/MPT/ VRD 等。4、其他：MM 导致的肾功能不全、染色体异常、高危、骨病明显、继发浆白、继发髓外浆细胞瘤、原发耐药、淀粉样变性、合并其他疾病（心功能不全、肺感染、肝功能不全、黄疸、糖尿病、高血压）、副作用预防和处理。耐药机制、联合用药。。。Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * 1、目的：生存时间和质量。长生存影响因素。目标：1、在可耐受的情况下，尽早获得CR；－早期CR 的意义；2、缓解症状，提高生活质量。2、很年轻- 序贯移植TT1~3；新药的应用；自体＋异基因。3、年老：部分也可移植，PAD+ASCT+LD ；其他VMP/VMPT/MPT/ VRD 等。4、其他：MM 导致的肾功能不全、染色体异常、高危、骨病明显、继发浆白、继发髓外浆细胞瘤、原发耐药、淀粉样变性、合并其他疾病（心功能不全、肺感染、肝功能不全、黄疸、糖尿病、高血压）、副作用预防和处理。耐药机制、联合用药。。。Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * 1、目的：生存时间和质量。长生存影响因素。目标：1、在可耐受的情况下，尽早获得CR；－早期CR 的意义；2、缓解症状，提高生活质量。2、很年轻- 序贯移植TT1~3；新药的应用；自体＋异基因。3、年老：部分也可移植，PAD+ASCT+LD ；其他VMP/VMPT/MPT/ VRD 等。4、其他：MM 导致的肾功能不全、染色体异常、高危、骨病明显、继发浆白、继发髓外浆细胞瘤、原发耐药、淀粉样变性、合并其他疾病（心功能不全、肺感染、肝功能不全、黄疸、糖尿病、高血压）、副作用预防和处理。耐药机制、联合用药。。。Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * 1、目的：生存时间和质量。长生存影响因素。目标：1、在可耐受的情况下，尽早获得CR；－早期CR 的意义；2、缓解症状，提高生活质量。2、很年轻- 序贯移植TT1~3；新药的应用；自体＋异基因。3、年老：部分也可移植，PAD+ASCT+LD ；其他VMP/VMPT/MPT/ VRD 等。4、其他：MM 导致的肾功能不全、染色体异常、高危、骨病明显、继发浆白、继发髓外浆细胞瘤、原发耐药、淀粉样变性、合并其他疾病（心功能不全、肺感染、肝功能不全、黄疸、糖尿病、高血压）、副作用预防和处理。耐药机制、联合用药。。。Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * EFS 5 年无病生存率CCR? Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * IFN ？Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * ？？？Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * 1、目的：生存时间和质量。长生存影响因素。目标：1、在可耐受的情况下，尽早获得CR；－早期CR 的意义；2、缓解症状，提高生活质量。2、很年轻- 序贯移植TT1~3；新药的应用；自体＋异基因。3、年老：部分也可移植，PAD+ASCT+LD ；其他VMP/VMPT/MPT/ VRD 等。4、其他：MM 导致的肾功能不全、染色体异常、高危、骨病明显、继发浆白、继发髓外浆细胞瘤、原发耐药、淀粉样变性、合并其他疾病（心功能不全、肺感染、肝功能不全、黄疸、糖尿病、高血压）、副作用预防和处理。耐药机制、联合用药。。。Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * * Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * * Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * * Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * * Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * * Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * * 7 patients in each group not evaluable: either not treated (n=5) or found to have no measurable disease at baseline by central laboratory assessment (n=9), despite having met eligibility criterion of measurable disease by local laboratory evaluation P-values shown for comparisons of EBMT response rates; calculated by stratified Cochran Mantel-Haemszel chi-squared test ORR by International Uniform Response Criteria including patients in response at last assessment (but unconfirmed) was 78% with VMP (12 additional patients) and 40% with MP (4 additional patients). Of 79 patients (23%) with stable disease by International Uniform Response Criteria, 4 (1%) were immunofixation-negative, and 19 (6%) had >50% reduction in M-protein in serum and/or urine; however, these patients were not recorded as PR because they did not fulfill all of the criteria, mainly because the confirmatory test was missing. Furthermore, 38 (11%) patients either had 25-49% reductions in M-protein or met the EBMT criteria for MR for non-secretory disease. Accordingly, only 18 (7%) patients were ‘true’non-responders. Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * * Descriptive P-values (stratified log-rank test) for the comparisons of duration of response: All responding patients –0.001 Patients achieving CR –0.097 The latter comparison does not result in a P-value indicating statistical significance as only 12 patients in the melphalan–prednisone arm achieved a complete response and not all of these patients have progressed. DOR p value 0.0012 for all responders, and 0.03 for patients with CR Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * * Median TTP by algorithm was 20.7 months with VMP and 15.2 months with MP (HR 0.54, P<0.001) In a post-hoc analysis using modified International Uniform Response Criteria (Facon), median TTP with VMP was not reached at 27 months Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * * Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * * Palumbo Lancet 2006 study measured OS from diagnosis, and excluded 76 patients (23%) who had less than 6 months of follow-up Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy * * VMP demonstrated consistently good efficacy in subgroups of patients with poor prognostic characteristics: age ≥75 years impaired renal function (creatinine clearance <60 mL/min) high-risk cytogenetics (t(4;14), t(14;16), or 17p deletion by FISH) In elderly patients vs younger patients: CR rate was slightly lower (26% vs 32%), TTP was identical, OS was slightly poorer (P=0.17) In patients with CrCl<60 mL/min vs ≥60 mL/min: CR rate (28% vs 32%), TTP, and OS appeared unaffected In patients with high-risk vs standard-risk cytogenetics: CR rate was identical (28%