伊布替尼联合化疗治疗复发难治原发性中枢神经系统淋巴瘤的初步探讨  

Preliminary exploration of ibrutinib combined with chemotherapy in the treatment of relapsed/refractory primary CNS lymphoma

作　　者：陈悦丹 刘焕光[2] 孙雪飞[1] 白雪燕[1] 崔衢[1] 邢瑞娴 王亚明[3] 孙胜军[4] 季楠[2] 刘元波[1] Chen Yuedan;Liu Huanguang;Sun Xuefei;Bai Xueyan;Cui Qu;Xing Ruixian;Wang Yaming;Sun Shengjun;Ji Nan;Liu Yuanbo(Department of Hematology,Beijing Tiantan Hospita1,Capital Medical University,Beijing 100070,China;Department of Neurosurgery,Beijing Tiantan Hospita1,Capital Medical University,Beijing 100070,China;Department of Neurosurgery,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;Department of Radiology,Beijing Tiantan Hospita1,Capital Medical University,Beijing 100070,China)

机构地区：[1]首都医科大学附属北京天坛医院血液科,100070 [2]首都医科大学附属北京天坛医院神经外科,100070 [3]首都医科大学宣武医院神经外科,北京100053 [4]首都医科大学附属北京天坛医院放射科,100070

出　　处：《中华神经外科杂志》2020年第10期1047-1051,共5页Chinese Journal of Neurosurgery

基　　金：首都卫生发展科研专项(2020-2-2049)。

摘　　要：目的初步探讨伊布替尼联合甲氨蝶呤、异环磷酰胺、多柔比星脂质体及甲泼尼龙(I-MIDD方案)治疗复发难治原发性中枢神经系统淋巴瘤(R/R PCNSL)患者的疗效及安全性。方法回顾性分析2017年9月至2019年12月首都医科大学附属北京天坛医院血液科收治的18例R/R PCNSL患者的临床资料。所有患者给予伊布替尼(560 mg/d,连用21 d)、甲氨蝶呤(3.5 g/m2,第1天)、异环磷酰胺(1.5 g/m2,第2天)、多柔比星脂质体(25 mg/m2,第3天)、甲泼尼龙(80 mg/d,第1~3天),每21天为1疗程,治疗1~6个疗程。参照2005年国际原发神经系统淋巴瘤合作组制定的疗效评价标准评价疗效,以完全缓解和部分缓解作为治疗有效的标准。根据美国卫生及公共服务部国立卫生研究院国家癌症研究所常见不良反应事件评价标准4.0版对药物相关不良反应进行评价。采用Kaplan-Meier法绘制生存曲线,分析患者的1年无进展生存率和总生存率。结果18例患者经(3.8±1.7)个(1~6个)周期I-MIDD方案治疗后,其中10例达到完全缓解,5例达到部分缓解,1例疾病稳定,2例疾病进展;总有效比例为15/18。18例患者的中位随访时间为13个月(3~27个月)。至末次随访,完全缓解6例,复发5例,进展6例,死亡1例。中位无进展生存期为6个月(1~27个月);总生存期为3~27个月。1年无进展生存率与总生存率分别为42.8%和87.4%。药物不良反应以骨髓抑制为主,24.6%(17/69例次)的患者出现白细胞、中性粒细胞及血小板计数减少(Ⅲ~Ⅳ级)。Ⅲ级非血液系统不良反应2例,其中真菌性肺炎1例,泌尿系感染1例;Ⅰ~Ⅱ级非血液系统不良反应21例。结论I-MIDD方案治疗R/R PCNSL的疗效和安全性均较好,或可作为R/R PCNSL的挽救治疗新方法。Objective To evaluate the effectiveness and safety of ibrutinib combined with methotrexate,ifosfamide,liposomal doxorubicin and methylprednisolone(I-MIDD regimen)for the treatment of relapse/refractory primary central nervous system lymphoma(R/R PCNSL).Methods The clinical data of 18 R/R PCNSL patients admitted to Department of Hematology,Beijing Tiantan Hospita1,Capital Medical University from September 2017 to December 2019 were analyzed retrospectively.All patients received ibrutinib(560 mg/d for 21 consecutive days),methotrexate(d1:3.5 g/m2),ifosfamide(d2:1.5 g/m2),liposomal doxorubicin(d3:25 mg/m2)and methylprednisolone(d1-3:80 mg/d)for chemotherapy.Every 21 days were considered as a course of treatment,and the patients were treated for 1-6 courses.The therapeutic effect of patients was evaluated according to the therapeutic evaluation criteria formulated by the international PCNSL collaborative group in 2005.Complete remission or partial remission was regarded as effective.Adverse drug reactions were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.Kaplan-Meier method was used to draw the survival curve,and the 1-year progression free survival rate and 1-year overall survival rate were evaluated.Results A total of 18 patients were treated with 3.8±1.7(1-6)courses of I-MIDD regimen,among them 10 patients achieved complete remission,5 achieved partial remission,1 had stable disease and 2 had progression of disease.The total effective rate was 15/18.The median follow-up time of 18 patients was 13(3-27)months.At the latest follow-up,6 patients achieved complete remission,5 had relapse,6 had progression and 1 died.The median progression-free survival(PFS)was 6(1-27)months,the overall survival(OS)ranged from 3 to 27 months,and the median OS was not achieved.The 1-year PFS and OS were 42.8%and 87.4%respectively.The adverse reaction of chemotherapy was mainly bone marrow suppression,and 17 out of 69(24.6%)adverse events were gradeⅢtoⅣleukopenia,neu

关 键 词：淋巴瘤 非霍奇金 中枢神经系统 复发 挽救疗法 抗肿瘤联合化疗方案 

分 类 号：R733.1[医药卫生—肿瘤]