维奈克拉方案治疗复发/难治性急性髓系白血病的临床研究  

A clinical study on the treatment of relapsed/refractory acute myeloid leukemia with venetoclax regimen

作　　者：雷芳[1] 费小明[1] 杨元林 季艳萍 余先球[1] 汤郁[2] Fang Lei;Xiaoming Fei;Yuanlin Yang;Yanping Ji;Xianqiu Yu;Yu Tang(Department of Hematology,Affiliated Hospital of Jiangsu University,Zhenjiang 212001,China;Department of Rheumatology,Affiliated Hospital of Jiangsu University,Zhenjiang 212001,China)

机构地区：[1]江苏大学附属医院血液科,江苏省镇江市212001 [2]江苏大学附属医院风湿科,江苏省镇江市212001

出　　处：《中国肿瘤临床》2024年第7期348-353,共6页Chinese Journal of Clinical Oncology

基　　金：江苏省社会发展重点项目(临床前沿技术)课题(编号:BE2020681);镇江市重点研发计划(社会发展)项目(编号:SH2022038)资助。

摘　　要：目的:评价维奈克拉(venetoclax,VEN)快速剂量递增、最长治疗时间为14天,联合低剂量阿糖胞苷(low-dose cytarabine,LDAC)方案挽救治疗复发/难治性急性髓系白血病(relapsed/refractory acute myeloid leukemia,R/RAML)的安全性和有效性。方法:回顾性分析2018年10月至2023年11月于江苏大学附属医院接受VEN+LDAC方案挽救治疗的16例R/R AML患者,所有患者既往均未接受过含VEN方案治疗。该方案VEN的剂量第1天为200 mg,其后均为400 mg固定剂量;LDAC 20 mg/m^(2)/d皮下注射。患者在治疗第8天复查骨髓,根据骨髓增生情况决定总疗程为10天还是14天。所有患者均不给予VEN单药治疗。有治疗反应的患者采用相同方案维持直到疾病进展或移植。结果:本研究纳入的R/R AML患者,中位随诊时间为27.5个月。治疗期间未发生有临床表现的肿瘤溶解综合症(tumor lysis syndrome,TLS)。治疗后总反应率(overall response rate,ORR)为68.75%,其中4例达完全缓解(complete response,CR),1例达血液学未恢复的完全缓解(CR with incomplete hematologic recovery,CRi),6例达部分缓解(partial response,PR)。达最佳疗效的治疗周期中位数为1个周期。中位总生存期(overall survival,OS)为5.8(0.5~47.2)个月,中位无进展生存期(progression-free survival,PFS)为22.2(7.3~42.9)个月。发生的不良反应主要为3~4级的血液学不良事件和感染。结论:本研究根据治疗第8天骨髓复查结果调整用药天数的VEN+LDAC方案,对于既往没有接受过含VEN方案治疗的R/R AML患者有较好的安全性和有效率。即使14天的VEN+LDAC治疗也是安全的。Objective:To explored the feasibility and efficacy of a rapid ramp-up,2-week maximum regimen of venetoclax(VEN)plus lowdose cytarabine(LDAC)for treating relapsed/refractory acute myeloid leukemia(R/R AML).Methods:We retrospectively analyzed patients with venetoclax-naïve R/R AML treated with VEN+LDAC between October 2018 and November 2023.On the first day,patients received 200 mg of VEN,and the dose was quickly increased to 400 mg for the rest of the treatment;cytarabine was administered subcutaneously at a low dose of 20 mg/m^(2)/day.The treatment duration was 10 or 14 days,depending on the condition of bone marrow hyperplasia determined on the 8th day of treatment.No patients received venetoclax monotherapy.All patients responding to salvage therapy received VEN+LDAC until disease progression or transplantation.Results:Among the patients,the median follow-up duration was 27.5 months.No clinical manifestations of tumor lysis syndrome(TLS)occurred during the treatment.The overall response rate(ORR)was 68.75%,including four complete responses(CR),one complete remission with incomplete hematologic recovery(CRi),and six partial responses(PR).The median number of best treatment result cycles was one cycle.The median overall survival(OS)in the whole cohort was 5.8(0.5-47.2)months;the median progression-free survival(PFS)was 22.2(7.3-42.9)months.The major adverse events were grade 3-4 hematologic adverse events and infections.Conclusions:The 8th-day myelosuppression-adjusted VEN+LDAC regimen is a feasible salvage option with a reasonable safety profile in patients with venetoclax-naïve R/R AML.Most patients tolerated the 14-day treatment;the response was generally rapid in the responding patients.

关 键 词：维奈克拉 低剂量 阿糖胞苷 复发/难治性急性髓系白血病 

分 类 号：R733.71[医药卫生—肿瘤]