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

Treatment options and prognosis in newly diagnosed multiple myeloma patients

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[接受常规化疗者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OS相关，多因素分析提示仅最大疗效达CR及VGPR是OS独立预后影响因素（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。

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 reeeieved 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 renfission （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.