初治多发性骨髓瘤患者治疗方案选择及疗效的预后意义研究

目的 探讨年龄<65岁[适合接受自体造血干细胞移植(ASCT)治疗]的多发性骨髓瘤(MM)患者治疗方案选择及其疗效反应的预后意义.方法 回顾性分析2005年6月至2009年12月收治的年龄<65岁的初发MM患者71例,其中一线接受ASCT治疗者21例(ASCT组),非移植组50例[接受常规化疔者30例(常规化疗组),接受硼替佐米为主新药方案治疗者20例(硼替佐米组)].根据各组患者治疗结果,分析治疗方案选择和疗效、疾病进展及生存率之间关系.结果 71例患者中位随访时间18(1～58)个月,预期3年总生存(OS)率为(79.8±6.3)%,无进展生存(PFS)率(54.8±9.0)%.诱导治疗后34例获得完全缓解(CR)或良好部分缓解(VGPR),硼替佐米组CR+VGPR率为80%(20例中有16例),明显高于常规化疗组的33.3%(30例中有10例)和ASCT组的38.1%(21例中有8例)(P<0.01).ASCT组移植后16例(76.1%)获得CR或VGPR,明显高于常规化疗组(P<0.01).常规化疗组、硼替佐米治疗组和ASCT组预期3年PFS率分别为(26.3±13.8)%(中位PFS期为21个月)、(40.5±20.1)%(中位PFS期为25个月)和(93.8±6.1)%(未达中位PFS期)(P=0.025).单因素分析发现诱导治疗获CR或VGPR(P=0.020)、最大疗效达CR及VGPR(P<0.01)、ASCT(P=0.002)和获最大疗效后维持治疗(P=0.0005)与患者PFS密切相关.诱导治疗方案和维持治疗与PFS无显著相关性.多因素分析提示仅ASCT治疗(P=0.039)和最大疗效达CR及VGPR(P=0.009)为PFS独立预后影响因素.常规化疗组、硼替佐米组和ASCT组3年预期OS率分别为(62.4±13.7)%、(94.1±5.7)%和(87.9±8.3)%,均未达中位值,差异无统计学意义(P=0.120).单因素分析提示诱导治疗获CR及VGPR(P=0.009)、最大疗效达CR及VGPR(P<0.01)、维持治疗(P=0.035)及获最大疗效后维持治疗(P=0.031)与0S相关,多因素分析提示仅最大疗效达CR及VGPR是OS独立预后影响冈素(P=0.005).结论 <65岁的初治MM患者最大疗效达CR及VGPR是OS和PFS独立预后影响因素,ASCT是PFS独立预后影响因素.硼替佐米为主的新药诱导治疗可迅速取得最佳疗效反应,ASCT后巩固治疗可提高患者最大疗效反应,并且获CR及VGPR后进行维持治疗具有更重要的意义.

Abstract：

Objective To explore the effect of treatment option on the response and outecomes in multiple myeloma ( MM) patients suitable for autologous hematopoietic stem cell transplantation ( autoHSCT). Methods A total of 71 newly-diagnosed MM patients less than 65 years admitted to Ruijin Hospital from June 2005 to December 2009 were analyzed retrospectively. Among them, 21 receieved auto-HSCT (HSCT group) with standard conditioning of melphalan 200 mg/m2, 30 received conventional chemotherapy (conventional group) and 20 received Bortezomib-based therapy (Bortezomib group). The responses and outcomes of different treatments were analyzed. Results The median follow-up duration for all patients was 18 (1 -58) months with estimated 3-year overall survival (3-yr OS ) of (79. 8 ± 6.3 ) % and progression-free survival (3-yr PFS) of (54.8 ±9.0)%. Thirty-four patients achieved complete remission (CR) or very good partial remission (VGPR) on induction therapy, which were 80% for the Bortezomib group, 33.3% for the conventional group and 38. 3% for the HSCT group. After auto-HSCT the CR + VGPR rate was increased to 76.1 % for the HSCT group. Overall, the 3-yr PFS was (26. 3 ± 13. 8) % ( median 21 months), (40. 5 ±20.1)% (median 25 months) and (93. 8 ± 6. 1)% ( median not reached, P = 0. 025 ) for conventional,Bortezomib and HSCT groups respectively. Univariate analysis demonstrated that CR/VGPR after induction ( P = 0.020), best response of CR/VGPR (P < 0.01), autoHSCT (P = 0.002) and maitenance therapy after CR/VGPR (P =0.0005) were associated with improved PFS and that CR/VGPR after induction (P =0.009), best response with CR/VGPR (P < 0.01), maintenance therapy for any patients (P = 0.035) and maintenance therapy for patients with CR/VGPR (P =0.031 ) were associated with OS. In multivariate analysis, only auto-HSCT (P =0.039) and best response of CR/VGPR (P =0.009) were independent prognostic factors for PFS and the best response of CR/VGPR was the only independent prognostic factor for OS (P =0.005). The estimated 3-yr OS was (62.4 ± 13. 7) % , ( 94. 1 ± 5. 7) % and (87. 9 ± 8. 3) % respectively for 3 groups. Conclusions For newly-diagnosed MM younger than 65 are suitable for auto-HSCT, the best response of CR/VGPR was associated with OS and PFS. Auto-HSCT is also important prognostic factor for PFS. Induction therapy with Bortezomib can achieve rapid CR/VGPR while auto-HSCT as a crucial consolidation therapy and maintenance therapy maybe also important for improvement of long-term outcome.

Treatment options and prognosis in newly diagnosed multiple myeloma patients

Objective To explore the effect of treatment option on the response and outecomes in multiple myeloma ( MM) patients suitable for autologous hematopoietic stem cell transplantation ( autoHSCT). Methods A total of 71 newly-diagnosed MM patients less than 65 years admitted to Ruijin Hospital from June 2005 to December 2009 were analyzed retrospectively. Among them, 21 receieved auto-HSCT (HSCT group) with standard conditioning of melphalan 200 mg/m2, 30 received conventional chemotherapy (conventional group) and 20 received Bortezomib-based therapy (Bortezomib group). The responses and outcomes of different treatments were analyzed. Results The median follow-up duration for all patients was 18 (1 -58) months with estimated 3-year overall survival (3-yr OS ) of (79. 8 ± 6.3 ) % and progression-free survival (3-yr PFS) of (54.8 ±9.0)%. Thirty-four patients achieved complete remission (CR) or very good partial remission (VGPR) on induction therapy, which were 80% for the Bortezomib group, 33.3% for the conventional group and 38. 3% for the HSCT group. After auto-HSCT the CR + VGPR rate was increased to 76.1 % for the HSCT group. Overall, the 3-yr PFS was (26. 3 ± 13. 8) % ( median 21 months), (40. 5 ±20.1)% (median 25 months) and (93. 8 ± 6. 1)% ( median not reached, P = 0. 025 ) for conventional,Bortezomib and HSCT groups respectively. Univariate analysis demonstrated that CR/VGPR after induction ( P = 0.020), best response of CR/VGPR (P < 0.01), autoHSCT (P = 0.002) and maitenance therapy after CR/VGPR (P =0.0005) were associated with improved PFS and that CR/VGPR after induction (P =0.009), best response with CR/VGPR (P < 0.01), maintenance therapy for any patients (P = 0.035) and maintenance therapy for patients with CR/VGPR (P =0.031 ) were associated with OS. In multivariate analysis, only auto-HSCT (P =0.039) and best response of CR/VGPR (P =0.009) were independent prognostic factors for PFS and the best response of CR/VGPR was the only independent prognostic factor for OS (P =0.005). The estimated 3-yr OS was (62.4 ± 13. 7) % , ( 94. 1 ± 5. 7) % and (87. 9 ± 8. 3) % respectively for 3 groups. Conclusions For newly-diagnosed MM younger than 65 are suitable for auto-HSCT, the best response of CR/VGPR was associated with OS and PFS. Auto-HSCT is also important prognostic factor for PFS. Induction therapy with Bortezomib can achieve rapid CR/VGPR while auto-HSCT as a crucial consolidation therapy and maintenance therapy maybe also important for improvement of long-term outcome.