真实世界初诊多发性骨髓瘤病人一线治疗方案的单中心、回顾性调查及疗效分析

发布时间：2018-06-28 18:05

本文选题：真实世界 + 多发性骨髓瘤　；参考：《河北医科大学》2017年硕士论文

【摘要】：目的:研究真实世界中,含硼替佐米方案与不含硼替佐米方案治疗多发性骨髓瘤疗效差异与安全性评估异同,同时分析多发性骨髓瘤病人的OS与PFS及其与硼替佐米累积剂量的关系,并讨论早期死亡和影响预后的可能因素。方法:选取2012年1月1日至2015年12月2日就诊于河北医科大学第三医院血液科初诊为多发性骨髓瘤(multiple myeloma,MM)的108例病人做为研究对象,按化疗治疗方案分为含硼替佐米组与不含硼替佐米组。含硼替佐米组37例病人,不含硼替佐米组71例病人,随访截止至2016年1月1日。硼替佐米组男性比例较高(73%vs48%,P=0.013),两方案组病人年龄、随访时间、MM分型、DS分期、ISS分期的差异均无统计学意义(P0.05)。结果:1硼替佐米组与非硼替佐米组疗效比较1.1硼替佐米组10例CR(27%),10例VGPR(27%),10例PR(27%),ORR达到81.1%;随访期间9例复发,其中1例2次复发;共死亡7例(6例为6个月内早期死亡);1.2非硼替佐米组12例CR(16.9%),9例VGPR(12.7%),29例PR(40.8%),ORR达到70.4%;随访期间36例复发,其中7例2次复发,1例3次复发;共死亡17例(3例为6个月内早期死亡);1.3两方案组疗效比较硼替佐米组总有效率ORR高于非硼替佐米组(81.1%对70.4%,P=0.230)且≥VGPR率高于非硼替佐米组(54.1%vs29.6%,P=0.013),但并未发现年龄因素对疗效的影响;1.4两方案组达最佳疗效(≥PR)所需疗程硼替佐米组中位2程,平均1.68程,1-4程;非硼替佐米组中位4程,平均4.2程,1-7程;疗程数比较p0.001;2缓解深度与pfs、os的关系两方案组删失率均小于70%,可行pfs生存分析;两方案组删失率均大于70%,中位os未达到;2.1硼替佐米组疗效达≥vgpr(中位pfs23个月)vsvgpr(中位pfs6个月),p=0.022;疗效达≥pr(中位pfs23个月)vspr(中位pfs2个月),p0.001,差异均有统计学意义;2.2非硼替佐米组疗效达≥vgpr(中位pfs24个月)vsvgpr(中位pfs12个月),p0.05,差异有统计学意义;疗效达≥pr(中位pfs17个月)vspr(中位pfs9个月),p=0.141,差异无统计学意义;2.3总体疗效达≥vgpr(中位pfs23个月)vsvgpr(中位pfs12个月),p0.05;疗效达≥pr(中位pfs18个月)vspr(中位pfs6个月),p0.005,差异均有统计学意义;3诱导及巩固治疗阶段硼替佐米累积量与pfs的关系硼替佐米中位累积剂量为15.6mg/m2。采用k-m(kaplanmeier)法绘制生存曲线,≥15.6mg/m2(17例)组pfs23个月与15.6mg/m2(20例)组pfs10个月,p=0.019;4mm病人pfs生存分析单因素分析结果示是否合并冠心病、是否进展为浆细胞白血病、初诊是否plt减少、初诊是否低白蛋白血症、初诊是否ldh250u/l的检验均p0.05,差异有统计学意义。将年龄(p=0.224)、方案分组(p=0.590)、issⅢ期(p=0.090)一同代入多因素分析,结果示应用硼替佐米为pfs保护因素,issⅢ期、年龄≥65岁、进展为浆细胞白血病、初诊低白蛋白血症、初诊ldh250u/l均为pfs危险因素,含硼替佐米组中位pfs比不含硼替佐米组约长10个月(23个月vs12个月,p=0.019);5mm病人早期死亡独立危险因素分析108例病人共有9例早期死亡,含硼替佐米组6例,不含硼替佐米组3例,单因素分析结果示方案分组(P=0.046)、是否合并冠心病(P=0.001)、是否PLT减少(P=0.017)、初诊是否LDH250 U/L(P=0.001)与早期死亡相关;多因素Logistic回归分析得出只有初诊LDH250 U/L(P=0.025,OR 0.157,95%CI 0.031-0.789)及合并冠心病(P=0.016,OR0.136,95%CI 0.027-0.686)为MM病人早期死亡独立危险因素;6化疗安全性评估评估显示,不含B组化疗后出现中性粒细胞减少(P=0.001)、贫血(P=0.001)及电解质紊乱(P0.001)的不良反应发生频率高,含B组化疗后出现PLT减少(P=0.006)的不良反应发生频率高。结论:1含硼替佐米方案组疗效优于不含硼替佐米方案,且达≥PR所需疗程短,反应速率快;2含硼替佐米方案疗效达PR可使病人PFS获益,而非硼替佐米组须达VGPR以上;3高累积剂量硼替佐米可延长MM病人的PFS;4含硼替佐米组中位PFS高出不含硼替佐米组约10个月(23个月VS12个月,P=0.019),而ISSⅢ期、年龄≥65岁、进展为浆细胞白血病、初诊低白蛋白血症、初诊LDH250 U/L均为PFS的危险因素;中位OS未达到;5初诊LDH250 U/L及合并冠状动脉粥样硬化性心脏病为MM病人早期死亡独立危险因素,硼替佐米不能降低早期死亡率;6含硼替佐米方案化疗后更易出现PLT减少,不含硼替佐米方案化疗后更易出现中性粒细胞减少、贫血及电解质紊乱;7本研究存在样本量偏少及单中心病员选择等限制,所得出结论未必全面,更好更有意义的结果需要扩大样本量及多中心合作来实现。
[Abstract]:Objective: To study the difference of efficacy and safety assessment between bortezomizomi scheme and bortezomizomi regimen in the real world in the treatment of multiple myeloma, and to analyze the relationship between OS and PFS and the cumulative dose of bortezomib in patients with multiple myeloma, and discuss the possible factors affecting early death and prognosis. Methods: 2012 From January 1st to December 2, 2015, 108 patients who were diagnosed as multiple myeloma (MM) in the Department of Hematology, Third Hospital of Hebei Medical University, were divided into bortezomizomi group and bortezomizomi group. 37 patients with bortezomizomi group and 71 patients without bortezomizomi group were followed up. By January 1, 2016, the male proportion of bortezomizomi group was higher (73%vs48%, P=0.013). There was no significant difference in age, follow-up time, MM typing, DS staging and ISS staging in two regimen group (P0.05). Results: 1 bortezomizomi group and non bortezomizomi group were more effective than 1.1 bortezomizomi group, 10 cases, CR (27%), 10 VGPR (27%), 10 PR (27%), ORR. Up to 81.1%, 9 cases relapsed during the follow-up period, of which 1 cases had 2 recurrence, and 7 cases died (6 cases were early death in 6 months); 1.2 non bortezomizo group 12 cases CR (16.9%), 9 cases (12.7%), 29 cases PR (40.8%) and ORR recurrence. The total effective rate of bortezomizomi group was higher than that of bortezomizomi group (81.1% to 70.4%, P=0.230) and the rate of VGPR was higher than that of non bortezomizomi group (54.1%vs29.6%, P=0.013), but the effect was not found by age factors; 1.4 two regimen group reached the best therapeutic effect (> PR) in the middle 2 course of the bortezomizomizomizomi group, the average 1.68 course, 1-4 course. The median 4 course of the non bortezomizo group, average 4.2 course, 1-7 course, p0.001, 2 remission depth and PFS, OS, the deletion rate of the two scheme group was less than 70%, the feasible PFS survival analysis; the two scheme group was more than 70%, the median OS was not reached; 2.1. The effect of bortezomizomi group was greater than vgpr (median pfs23 months) vsvgpr (median pfs6 month), p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; p=0.022; therapy Pr (median pfs23 months) vspr (median pfs2 months), p0.001, the difference was statistically significant; 2.2 the effect of non bortezomizomi group was greater than vgpr (median pfs24 months) vsvgpr (median pfs12 month), P0.05, the difference was statistically significant; the curative effect reached > pr (median pfs17 month), the difference was not statistically significant; the 2.3 population was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; the difference was not statistically significant; 2.2 The curative effect was more than vgpr (median pfs23 months) vsvgpr (median pfs12 months) and P0.05; the curative effect was greater than pr (median pfs18 months) vspr (median pfs6 months), P0.005, and the difference was statistically significant; 3 the cumulative dose of bortezomizomizomi and PFS were induced and consolidated at the stage of treatment. The survival curve, 15.6mg/m2 (17 cases) (20 cases) and 15.6mg/m2 (20 cases) group pfs10 months, p=0.019; 4mm patients PFS survival analysis single factor analysis results showed whether the combination of coronary heart disease, whether progression to plasma cell leukemia, first diagnosis of PLT reduction, first diagnosis of hypoalbuminemia, the first diagnosis of ldh250u/l is P0.05, the difference is statistically significant P0.05, the difference is statistically significant Age (p=0.224), scheme grouping (p=0.590) and ISS III (p=0.090) were combined into multiple factors analysis. The results showed that bortezomib was a PFS protective factor, ISS III, age more than 65 years old, progressing to plasma cell leukemia, early diagnosis of hypoalbuminemia, and primary diagnosis of ldh250u/l as a risk factor for PFS, and the median PFS ratio in the bortezomizomi group was not borosilia. The Zomi group was about 10 months (23 months vs12 months, p=0.019); the independent risk factors for early death of 5mm patients were analyzed in 108 patients with 9 early deaths, 6 cases of bortezomizomi group and 3 cases without bortezomizomi group. The single factor analysis showed the scheme grouping (P=0.046), whether or not coronary heart disease (P=0.001), PLT decrease (P=0.017), and first diagnosis of LDH2 50 U/L (P=0.001) was associated with early death; multiple factor Logistic regression analysis showed that only primary LDH250 U/L (P=0.025, OR 0.157,95%CI 0.031-0.789) and combined coronary artery disease (P=0.016, OR0.136,95%CI 0.027-0.686) were independent risk factors for early death. 6 chemotherapy safety assessment assessment showed no neutrophils after chemotherapy. Cytosolic (P=0.001), anemia (P=0.001) and electrolyte disorder (P0.001) have a high frequency of adverse reactions, and the adverse reaction of PLT reduction (P=0.006) in the group B after chemotherapy is high. Conclusion: 1, bortezomizomi regimen is better than bortezomib without bortezomizomi scheme, and the treatment course is shorter and the rate of reaction is faster than that of the group of borosomizomizomi, and 2 the treatment of bortezomizomi scheme. PR could benefit the patient's PFS, while the non bortezomizomi group was more than VGPR; 3 the high cumulative dose of bortezomib could prolong the PFS of the patients with MM; 4 the median bortezomizomi group was higher than the bortezomizomi group for about 10 months (23 months VS12, P=0.019), and the ISS III, the age of more than 65 years, was progressing to plasma cell leukemia, first diagnosis of hypoalbuminemia. LDH250 U/L was a risk factor for PFS; median OS was not reached; 5 first diagnosis of LDH250 U/L and coronary atherosclerotic heart disease were independent risk factors for early death of MM patients. Bortezomizomi could not reduce early mortality; 6 the bortezomizomi regimen was more susceptible to PLT reduction after chemotherapy, and no bortezomizomi regimen was more likely to occur after chemotherapy. Neutrophils, anemia and electrolyte disorders; 7 there are limited samples and choice of single center patients. The results are not necessarily comprehensive, and better and more meaningful results need to be achieved by expanding the sample size and multi center cooperation.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R733.3

【参考文献】