利妥昔单抗减量的FCR方案一线治疗慢性淋巴细胞白血病疗效分析  

Efficacy and safety of frontline FCR(fludarabine, cyclophosphamide, rituximab) with dose reduction of rituximab in chronic lymphocytic leukemia

作　　者：罗菁 张佼佼 张兴利 陈丽[1] 糜坚青 LUOJing;ZHANG Jiaojiao;ZHANG Xingli;CHEN Li;MI Jianqing(Shanghai Institute of Hematology,State Key Laboratory of Medical Genomics,National Re-search Center for Translational Medicine at Shanghai,Department of Hematology,Ruijin Hos-pital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai,200025,China;Department of Hematology,the Third People's Hospital of Kunshan)

机构地区：[1]上海血液学研究所,国家医学基因重点实验室,国家转化医学研究中心,上海交通大学医学院附属瑞金医院血液科,上海200025 [2]江苏省昆山市第三人民医院血液科

出　　处：《临床血液学杂志》2022年第9期645-649,共5页Journal of Clinical Hematology

摘　　要：目的:分析利妥昔单抗减量(375 mg/m~2固定剂量)的氟达拉滨+环磷酰胺+利妥昔单抗(FCR)方案一线治疗慢性淋巴细胞白血病(CLL)的疗效,并探讨影响疗效的预后因素。方法:回顾性分析2009年9月—2021年6月在我院接受一线利妥昔单抗减量FCR方案治疗的35例CLL患者的临床资料。结果:35例患者中男25例,女10例,中位年龄58(42~75)岁,中位疗程数为6(2~6)个,总反应率为91.4%(32/35),15例(42.9%)达完全缓解,3例(8.6%)达骨髓未恢复的完全缓解,14例(40.0%)达部分缓解,2例(5.7%)疾病稳定,1例(2.9%)疾病进展。20例患者进行了骨髓微小残留病(MRD)检测,14例(70.0%)MRD阴性(MRD<0.01%)。中位随访60.7(6.6~153.4)个月,中位无进展生存期为61.7(95%CI 57.7~106.9)个月,中位总生存期未达到。Cox回归分析发现,患者血清β2-微球蛋白>3.5 mg/L和伴有TP53异常是影响无进展生存期的独立不良预后因素(P<0.05),未发现对总生存期有意义的影响因素。单因素分析发现,治疗前IgA缺乏患者的总生存期显著缩短(P<0.05);治疗后达骨髓MRD阴性患者的无进展生存期显著延长(未达到vs 35.6个月,P=0.016)。治疗后7例(20.0%)发生≥3级感染,15例(42.9%)发生≥3级血液学不良反应,除1例发生5级不良反应,其余不良反应均可恢复。结论:利妥昔单抗减量的FCR方案一线治疗CLL患者的总反应率、MRD转阴率及远期生存获益较理想,安全性可控。患者治疗前血清β2-微球蛋白>3.5 mg/L和伴有TP53异常影响无进展生存期,治疗前IgA缺乏可能影响总生存期;治疗后达骨髓MRD阴性的患者更易获得长期无进展生存。Objective: To investigate the efficacy and safety of the FCR regimen(fludarabine, cyclophosphamide and rituximab) with dose reduction of rituximab(375 mg/m~2fixed dosage) in treatment-naive patients with chronic lymphocytic leukemia(CLL). Methods: The clinical data of 35 CLL patients treated with frontline rituximab-reduced FCR regimen in our hospital from September 2009 to June 2021 were collected and analyzed. Results: The median age before treatment initiation was 58(42-75) years in 35 patients, with 25 males and 10 females. The median treatment course was 6(2-6). The overall response rate was 91.4%(32/35), 15 cases(42.9%) achieved complete response, 3 cases(8.6%) achieved complete response with incomplete marrow recovery, 14 cases(40.0%) achieved partial response, 2 cases(5.7%) were in stable disease and 1 case(2.9%) had progressive disease. The bone marrow measurable residual disease(MRD) was detected in 20 patients, of which 14 cases(70.0%) achieved MRD negative(MRD<0.01%). The median follow-up time was 60.7(6.6-153.4) months, the median progression-free survival was 61.7(95%CI 57.7-106.9) months, and median overall survival was not reached. Cox regression analysis showed that serum β2-microglobulin>3.5 mg/L and TP53 abnormalities before treatment initiation were independent prognostic factors of progression-free survival(P<0.05). No independent prognostic factors of overall survival were identified, but IgA deficiency was significantly correlated with shorter overall survival in univariate analysis(P<0.05). Patients achieved bone marrow MRD negative post-treatment had a significant prolongation in progression-free survival(not reached vs 35.6 months, P=0.016). Seven cases(20.0%) experienced ≥grade 3 infection post-treatment and 15 cases(42.9%) experienced ≥grade 3 hematologic adverse events. All adverse events were resolved and recovered other than 1 case of grade 5 adverse events. Conclusion: FCR regimen with does reduction of rituximab results in a high response rate and undetectable MRD rate with g

关 键 词：慢性淋巴细胞白血病 氟达拉滨 环磷酰胺 利妥昔单抗 减低剂量 

分 类 号：R733.72[医药卫生—肿瘤]