BAD和BDD方案诱导化疗新诊断活动性多发性骨髓瘤患者的临床疗效分析

Effect of regimens of induction chemotherapy by BAD and BDD for patients with newly diagnosed active multiple myeloma

目的评价BAD(硼替佐米+多柔比星+地塞米松)和BDD(硼替佐米+脂质多柔比星+地塞米松)方案,对新诊断活动性多发性骨髓瘤(MM)患者诱导化疗的有效性及安全性。方法选择2015年1月至2019年6月,于绵阳市第三人民医院血液科确诊并采用BAD或BDD方案诱导化疗的80例新诊断活动性MM患者为研究对象。其中,男性患者为49例,女性为31例;中位年龄为57.5岁(51.2~63.8岁)。按照化疗方案不同,将其分为BAD组(n=47)和BDD组(n=33)。对患者的随访日期截至2020年3月31日。回顾性分析并比较2组患者的一般临床资料。治疗后,2组患者的高质量缓解率和总反应率(ORR)比较采用χ^(2)检验。采用Kaplan-Meier法绘制2组患者的无进展生存(PFS)和总体生存(OS)曲线,并使用log-rank检验比较2组患者的PFS和OS期。采用χ^(2)检验或Fisher精确概率法比较2组患者治疗后不同级别不良反应发生率。本研究经绵阳市第三人民医院医学伦理委员会批准(批准文号:2205391),并与所有受试者及家属签署临床研究知情同意书。结果①BAD组和BDD组患者年龄,性别、MM类型、国际分期系统(ISS)分期、美国东部肿瘤协作组(ECOG)-体力状况(PS)构成比,以及骨髓浆细胞比例等一般临床资料分别比较,差异均无统计学意义(P>0.05)。②BAD组MM患者接受诱导化疗的中位疗程数为4个(2~7个),BDD组为5个(2~8个),2组比较,差异无统计学意义(Z=—0.687,P=0.492);2组患者的高质量缓解率[44.7%(21/47)比54.5%(18/33)]、ORR[80.9%(38/47)比87.9%(29/33)]分别比较,差异均无统计学意义(χ^(2)=0.755、0.704,P=0.385、0.402)。③中位随访时间24.5个月(6.0~61.0个月),BAD组患者的中位PFS和OS期分别为32.0个月(95%CI:29.2~34.8个月)和37.0个月(95%CI:24.4~49.6个月),与BDD组的35.0个月(95%CI:31.2~38.8个月)和51.0个月(95%CI:32.8~69.2个月)分别比较,差异均无统计学意义(χ^(2)=2.617、1.247,P=0.106、0.264)。④血液学不良反应方面,2组患者所有级别(1~5级)和3~5级白细胞减少(70.2%比60.6%,36.2%比30.0%),中性粒细胞减少(63.8%比57.6%,23.4%比21.2%)及血小板减少(66.0%比60.6%,40.4%比36.4%)发生率分别比较,差异均无统计学意义(P>0.05)。非血液学不良反应方面,与BAD组比较,BDD组患者心脏毒性(所有级别:12.1%比31.9%,χ^(2)=4.194,P=0.041;3~5级:3.0%比21.3%,χ^(2)=4.013,P=0.045),脱发(所有级别:21.2%比53.2%,χ^(2)=8.261,P=0.004;3~5级:9.1%比34.0%,χ^(2)=6.665,P=0.010),恶心(所有级别:33.3%比57.4%,χ^(2)=4.520,P=0.033;3~5级:9.1%比27.7%,χ^(2)=4.178,P=0.041),呕吐(所有级别:18.2%比40.4%,χ^(2)=4.465,P=0.035;3~5级:6.1%比23.4%,χ^(2)=4.285,P=0.038)发生率均显著降低,并且差异均有统计学意义。结论BDD方案诱导化疗新诊断活动性MM患者的总体疗效与BAD方案相当,但是前者非血液系统不良反应发生率较后者显著降低,可以减轻患者心脏毒性,降低脱发和胃肠道反应的发生风险。BDD方案是BAD方案的良好替代方案,可作为临床上诱导化疗新诊断活动性MM患者的优先选择之一。

Objective To evaluate the efficacy and safety of regimens of induction chemotherapy by bortezomib-adriamycin-dexamethasone(BAD)and bortezomib-doxil-dexamethasone(BDD)for patients with newly diagnosed active multiple myeloma(MM).Methods From January 2015 to June 2019,a total of 80 patients with newly diagnosed active MM who were diagnosed at the Department of Hematology,Mianyang Third People′s Hospital were selected as research subjects.There were 49 male patients and 31 females.And the median age of them were 57.5 years(51.2-63.8 years).They were divided into BAD group(n=47)and BDD group(n=33)according to their chemotherapy regimen.The patient′s follow-up date was up to March 31,2020.The general clinical data of patients in both group were retrospectively analyzed and compared.The high-quality response rate and total response rate(ORR)of patients after treatment in two groups were calculated,and the differences between the two groups were compared by Chi-square test.The Kaplan-Meier method was used to draw the progression-free survival(PFS)and overall survival(OS)curves in both groups,and the log-rank test was used to compare the differences in PFS and OS time between two groups.The Chi-square test or Fisher′s exact probability test was used to compare the occurrence rate of adverse reactions with different degrees between two groups.This study was approved by the Medical Ethics Committee of Mianyang Third People′s Hospital(Approval No.2205391).Informed consent was obtained from all participants or these family members.Results①There were no statistically significant differences in general clinical data such as age,composition ratio of gender,immunotype,International Staging System(ISS)stage,Eastern Coorperative Oncology Group(ECOG)-Performance Status(PS),and proportion of bone marrow plasma cell between BAD and BDD group(P>0.05).②The median number of treatment courses for MM patients in BAD group was 4 courses(2-7 courses),which was 5 courses(2-8 courses)in BDD group,the difference was not statistically significant between them(Z=—0.687,P=0.492).There was no statistically significant difference in high-quality response rate[44.7%(21/47)vs 54.5%(18/33)],and ORR[80.9%(38/47)vs 87.9%(29/33)]between two groups(χ^(2)=0.755,0.704;P=0.385,0.402).③The median follow-up time was 24.5 months(6-61 months).The median PFS and OS time in BAD group were 32.0 months(95%CI:29.2-34.8 months)and 37.0 months(95%CI:24.4-49.6 months),which were 35.0 months(95%CI:31.2-38.8 months)and 51.0 months(95%CI:32.8-69.2 months)in BDD group,the differences were not statistically significant between two groups(χ^(2)=2.617,1.247;P=0.106,0.264).④In terms of hematological adverse reactions,there were no statistically significant differences in the incidence of white blood cells with all degrees(degree 1-5)and degree 3-4(70.2%vs 60.6%,36.2%vs 30.0%),neutrophils(63.8%vs 57.6%,23.4%vs 21.2%)and thrombocytopenia(66.0%vs 60.6%,40.4%vs 36.4%)between two groups(P>0.05).In terms of non-hematological adverse reactions,the incidence of cardiotoxicity(all degrees:12.1%vs 31.9%,χ^(2)=4.194,P=0.041;degree 3-5:3.0%vs 21.3%,χ^(2)=4.013,P=0.045),hair loss(all degrees:21.2%vs 53.2%,χ^(2)=8.261,P=0.004;degree 3-5:9.1%vs34.0%,χ^(2)=6.665,P=0.010),nausea(all degrees:33.3%vs 57.4%,χ^(2)=4.520,P=0.033;degree 3-5:9.1%vs 27.7%,χ^(2)=4.178,P=0.041),vomiting(all degrees:18.2%vs 40.4%,χ^(2)=4.465,P=0.035;degree 3-5:6.1%vs 23.4%,χ^(2)=4.285,P=0.038)in BDD group were obviously lower than those of BAD group,and all the differences were statistically significant.Conclusions The overall efficacy of BDD regimen in induction chemotherapy for patients with newly diagnosed active MM is equivalent to that of BAD regimen,but the former has a significantly lower incidence of non-hematological adverse reactions than the latter,which can reduce the cardiotoxicity and decrease the risk of hair loss and gastrointestinal reactions.The BDD regimen is a good alternative to the BAD regimen,which can be used as one of the best choices in induction chemotherapy for patients with newly diagnosed active MM.