调整剂量的达妥木单抗联合DCEP治疗硼替佐米和来那度胺双耐药的多发性骨髓瘤

Dose-adjusted daratumumab combined with DCEP in treatment of multiple myeloma dual-refractory to bortezomib and lenalidomide

目的:探索调整剂量的达妥木单抗联合地塞米松、环磷酰胺、依托泊苷、顺铂(dose adjustment daratumumab with dexamethasone,cyclophosphamide,etoposide,cisplatin,DA-DDCEP)方案治疗硼替佐米和来那度胺双耐药的多发性骨髓瘤(multiple myeloma,MM)患者的疗效和安全性。方法:回顾性收集2020年3月至2022年9月,本院血液科接受DA-DDCEP方案治疗的硼替佐米和来那度胺双耐药的MM患者共17例。统计分析治疗的总反应率(overall response rate,ORR)、最佳缓解率、无进展生存(progression-free survival,PFS)和总生存(overall survival,OS)时间,探讨治疗后反应、美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)体能状态、是否伴髓外病变对生存的影响。收集治疗相关的血液学及非血液学毒性发生情况。结果:17例患者平均年龄(63.2±10.0)岁,男性8例(47%),中位治疗线数5(3~8)线。经过中位4(2~14)个疗程,患者ORR为65%,其中完全缓解(complete response,CR)率18%。中位随访26(11~40)个月,中位PFS期和OS期分别为8个月和12个月。治疗后是否取得治疗反应,对生存有显著影响,达PR及以上疗效和无治疗反应的PFS期分别为14个月和2个月(P=0.000),OS期分别为19个月和7个月(P=0.05)。ECOG体能状态对生存影响不大,ECOG评分≤2分和>2分的中位PFS期和OS期分别为8个月比7个月(P=0.863)和19个月比10个月(P=0.615)。复发伴髓外病变和不伴髓外病变的PFS期和OS期分别6个月比14个月(P=0.009)和9个月比19个月(P=0.187)。3~4级的不良反应包括中性粒细胞减少8例(47%)、贫血8例(47%)、淋巴细胞减少9例(53%)、血小板减少9例(53%)。肺部感染5例(29%),均为2级,2例患者发生乙型肝炎(乙肝)再激活。结论:DA-DDCEP方案治疗硼替佐米和来那度胺双耐药的复发MM患者有效。ECOG体能状态较差的患者能耐受并可获益,复发伴髓外病变患者的生存仍有待提高。整体安全性良好,需注意监测乙肝病毒。

Objective To explore the efficacy and safety of dose adjustment daratumumab with dexamethasone,cyclophosphamide,etoposide,cisplatin(DA-DDCEP)regimen in the patients with multiple myeloma(MM)dual-refractory to bortezomib and lenalidomide.Methods From March in 2020 to September in 2022,a total of 17 patients from the department of hematology of our hospital were included in this retrospective study.The overall response rate(ORR),optimal response rate,progression-free survival(PFS),and overall survival(OS)time were statistically analyzed,and the effect of different treatment responses,Eastern Cooperative Oncology Group(ECOG)physical status,and whether accompanied by extramedullary diseases(EMD)on survival were eveluated.Hematologic and nonhematologic toxicity associated with treatment were observed.Results In 17 patients with a mean age of(63.2±10.0)years,eight(47%)were males and a median treatment line number was 5(3-8).After a median cycle of 4(2-14),the ORR and complete response(CR)rates were 65%and 18%.After median follow-up months of 26(11-40),the median PFS and OS time were 8 and 12 months,respectively.The response to the treatment had a significant impact on survival.Comparing response[≥(partial response,PR)]with non-response patients,PFS was 14 months vs.2 months(P=0.000)and OS was 19 months vs.7 months(P=0.05).The ECOG physical state has no impact on survival,comparing ECOG score≤2 with>2 patients,PFS was 8 months vs.7 months(P=0.863)and OS was 19 months vs.10 months(P=0.615).Contrasting relapse with EMD or without EMD,PFS was 6 months vs.14 months(P=0.009)and OS was 9 months vs.19 months(P=0.187),respectively.Grade 3-4 adverse events included 8 case(47%)neutropenia,8 case(47%)anemia,9 case(53%)lymphocytopenia and 9 case(53%)thrombocytopenia.There were 5 cases(29%)of pulmonary infection,all of which were grade 2.In addition,hepatitis B reactivation occurred in two patients.Conclusions DA-DDCEP regimen is effective in myeloma patients dual-refractory to bortezomib and lenalidomide,and the patients with poor ECOG physical status can tolerate the treatment and benefit from it.The survival of patients with EMD still need to be improved.Overall safety is good,but hepatitis B virus should be monitored carefully.