复发/难治DLBCL患者继发CNS侵犯的临床特征及泽布替尼联合化疗方案的疗效  

Clinical features of secondary central nervous system involvement in 4 patients with relapsed/refracto⁃ry diffuse large B-cell lymphoma and the efficacy of Zanubrutinib combined regimen

作　　者：石磊[1] 王亚丽 孙恺 陆敏秋[1] 高珊[1] 褚彬[1] 王宇彤 鲍立[1] SHI Lei;WANG Yali;SUN Kai;LU Qiumin;GAO Shan;CHU Bin;WANG Yutong;BAO Li(Department of Hematology,Beijing Jishuitan Hospital,Beijing 100096,China;不详)

机构地区：[1]北京积水潭医院血液科,北京100096 [2]北京天坛医院神经肿瘤综合治疗病区

出　　处：《山东医药》2022年第19期28-32,共5页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(81971508)。

摘　　要：目的分析4例继发中枢神经系统(CNS)侵犯的复发/难治弥漫大B细胞淋巴瘤(DLBCL)患者的临床特征,并观察泽布替尼联合化疗方案的疗效。方法选择4例DLBCL继发CNS侵犯患者,分析其初诊及复发时的临床特征;并进行相应泽布替尼联合化疗方案治疗,其中,2例采用泽布替尼+甲氨蝶呤(Z-MTX)方案治疗,1例采用泽布替尼+利妥昔单抗+吉西他滨+顺铂+地塞米松(Z-R-GDP)方案治疗,1例采用泽布替尼+利妥昔单抗+甲氨蝶呤(ZR-MTX)方案治疗,评价治疗方案的疗效及毒性反应。结果4例患者中,3例CNS复发仅侵犯脑实质,另1例同时侵犯脑、眼;3例具有淋巴瘤中枢侵袭的高危中枢神经系统国际预后指数(CNS-IPI)评分(4~6分),另1例CNS-IPI评分1分。3例患者为非生发中心(non-GCB)来源,其中MCD亚型2例、非MCD亚型1例;1例未进行相关分子生物学检查。化疗后完全缓解3例,部分缓解1例;随访4~5个月,至末次随访,3例完全缓解患者疗效持续缓解无复发,1例部分缓解患者复发。主要毒性反应为血液学毒性,未发生肿瘤溶解、心房颤动或高血压等其他3级及以上布鲁顿氏酪氨酸激酶选择性抑制剂相关的毒性反应。结论复发/难治DLBCL继发CNS侵犯多为non-GCB来源及MCD亚型,主要侵犯脑实质;泽布替尼联合化疗方案有显著、持续的疗效和生存优势,其主要毒性反应可控。Objective To summarize the clinical features of secondary central nervous system(CNS)involvement in 4 patients with relapsed/refractory diffuse large B-cell lymphoma(DLBCL),and to investigate the efficacy and safety of Zanubrutinib combined regimen.Methods We selected 4 patients with CNS involvement secondary to DLBCL.The clinical data were collected and the clinical features of the patients at the initial diagnosis and recurrence were analyzed.The efficacy and adverse events of Zanubrutinib combined regimen were followed up.Patients 1 and 2 were treated with Zanubrutinib+Methotrexate(Z-MTX),patient 3 was treated with Zanubrutinib+Rituximab+Gemcitabine+Cisplatin+Dexamethasone(Z-R-GDP),and patient 4 was treated with Zanubrutinib+Rituximab+Methotrexate(Z-R-MTX).We evaluated the efficacy and toxic reaction of the regimen.Results Among the 4 patients,3 cases had CNS involvement in the brain parenchyma,and the other 1 case in the brain and eyes at the same time,and 3 had high-risk CNS-IPI score(4-6 points)at initial diagnosis,and the other 1 case had 1 point of CNS-IPI score.Three patients were non-GCB,including 2 cases of MCD subtype and 1 case of non-MCD subtype;1 case did not receive relevant molecular biological examination.After all 4 patients were treated with Zanubrutinib combined regimen,3 cases achieved completely response and 1 case achieved partially response.The patients were followed up for 4-5 months,as of the last follow-up,3 cases with complete response had sustained response and no relapse and 1 case with partially response had relapsed.The major toxic reaction was hematologic toxicity,and no other grade 3 or higher BTK inhibitor-related toxic reactions such as atrial fibrillation occurred.Conclusions The CNS involvement secondary to DLBCL mostly comes from non-GCB and is MCD subtype,which mainly invades the brain.Zanubrutinib combination regimen is an effective and safe regimen for the CNS involvement secondary to DLBCL,and its main toxic reactions are controllable.

关 键 词：复发/难治弥漫大B细胞淋巴瘤 中枢神经系统侵犯 泽布替尼 布鲁顿氏酪氨酸激酶选择性抑制剂 

分 类 号：R733[医药卫生—肿瘤]