硼替佐米联合环磷酰胺及地塞米松方案治疗多发性骨髓瘤

Effects of bortezomib in combination with cyclophosphamide and dexamethasone in the treatment of multiple myeloma

目的观察硼替佐米联合环磷酰胺及地塞米松(VCD)方案治疗多发性骨髓瘤(MM)患者的疗效和安全性。方法回顾性分析2012年6月至2017年6月收治的55例应用VCD方案治疗初治及复发难治的MM患者资料。结果患者应用VCD中位疗程为4(2～8)个。治疗的总体缓解率(ORR)为85.5%(45/55),其中完全缓解及接近完全缓解(CR/nCR)率为27.3%,非常好的部分缓解(VGPR)率为23.6%,部分缓解(PR)率34.6%;合并肾功能不全的10例患者总有效率80.0%,45例肾功能正常患者的总有效率为82.2%,两者差异无统计学意义(P=0.627)。中位随访13.5(1～61)个月,预计中位无进展生存(PFS)时间27(1～61)个月,中位缓解持续(DOR)时间18(1～50)个月,中位总体生存(OS)时间49(1～64)个月。单因素分析中,ISS分期Ⅲ期、难治复发、疗效未达VGPR及肾功能异常是影响PFS的不良因素;ISS分期Ⅲ期及肾功能异常是影响OS的不良因素。多因素分析中,ISS分期Ⅲ期及疗效未达VGPR是PFS的独立影响因素;ISS分期Ⅲ期是OS的独立影响因素。安全性分析显示VCD方案具有良好的安全性及耐受性,统计其不良反应,最常见的3/4级非血液学不良反应为感染(20.0%)、周围神经病变(5.5%)、高血压(5.5%)。最常见的3/4级血液学不良反应为血小板减少(10.9%)、中性粒细胞减少(9.0%)和贫血(5.5%)。共有2例(3.6%)患者因严重的神经毒性更换治疗方案,2例患者因肺部感染导致呼吸衰竭死亡(3.6%)。结论 VCD方案在初治/复发难治患者中有效率高,不良反应可以接受,对合并肾功能不全的患者可安全应用。

Objective To retrospectively analyze the clinical efficacy and safety of VCD(bortezomib/ cyclophosphamide/dexamethason) in the treatment of multiple myeloma (MM) patients. Methods Fifty - five consecutive patients with newly diagnosed or relapsed MM were enrolled in the study retrospectively from June 2012 to June 2017. We collected and analyzed the clinical information of all patients treated with VCD. Results Firstly,the patients received therapy of VCD for median 4 cycles(Range:2 ~ 8). The overall response rate(ORR)was 85.5%(45/55). The complete response/near complete response rate(CR/nCR),very good partial response rate(VGPR)and partial response rate(PR)were 27.3%,23.6% and 34.6%,respectively. The ORR of 10 patients with renal inadequacy was 80.0%,while 45 cases with normal renal function was 82.2%(P=0.627). Secondly,with a median follow - up of 13.5 months,the median progression free survival(PFS),the median duration of response(DOR)and the median overall survival(OS)were 27(1 ~ 61)months,18(1 ~ 50)months and 49(1 ~ 64)months,respectively.Univariate prognostic analysis showed that abnormal ISS stage Ⅲ,relapse, renal dysfunction and response inferior to VGPR were negative prognostic factors for PFS,while abnormal ISS stage Ⅲ and renal dysfunction were negative prognostic factors for OS. Moreover,the multivariate prognostic analysis showed that abnormal ISS stage Ⅲ and response inferior to VGPR were independent prognostic factors for PFS,while ISS stage Ⅲ was independent prognostic factors for OS. Thirdly,the VCD treatment is effective and safe. The adverse events were evaluated according to International Myeloma Working Group Uniform Response Criteria. The results showed that the most common grade 3 ~ 4 non - hematology adverse events(AEs) were infection (20.0%),peripheral neuropathy(5.5%)and hypertension(5.5%). The most common grade 3 ~ 4 hematology AEs were thrombocytopenia(10.9%),neutropenia(9.0%)and anemia(5.5%). A total of 2 patients(3.6%) discontinued VCD because of serious peripheral neuropathy and 2 cases(3.65%) died of respiratory failure because of serious infection. Conclusions The VCD regimen is effective and safe in the treatment of newly diagnosed or relapsed/refractory MM patients in China. VCD is safe in patients with renal dysfunction.