BTK抑制剂治疗原发免疫豁免部位大B细胞淋巴瘤的研究进展

丁彬彬 李子坚

丁彬彬, 李子坚. BTK抑制剂治疗原发免疫豁免部位大B细胞淋巴瘤的研究进展[J]. 中国肿瘤临床, 2023, 50(22): 1174-1179. doi: 10.12354/j.issn.1000-8179.2023.20231013
引用本文: 丁彬彬, 李子坚. BTK抑制剂治疗原发免疫豁免部位大B细胞淋巴瘤的研究进展[J]. 中国肿瘤临床, 2023, 50(22): 1174-1179. doi: 10.12354/j.issn.1000-8179.2023.20231013
Binbin Ding, Zijian Li. Research on Bruton’s tyrosine kinase inhibitor for the treatment of primary immune-privileged site large B-cell lymphoma[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2023, 50(22): 1174-1179. doi: 10.12354/j.issn.1000-8179.2023.20231013
Citation: Binbin Ding, Zijian Li. Research on Bruton’s tyrosine kinase inhibitor for the treatment of primary immune-privileged site large B-cell lymphoma[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2023, 50(22): 1174-1179. doi: 10.12354/j.issn.1000-8179.2023.20231013

BTK抑制剂治疗原发免疫豁免部位大B细胞淋巴瘤的研究进展

doi: 10.12354/j.issn.1000-8179.2023.20231013
详细信息
    作者简介:

    丁彬彬:专业方向为血液肿瘤的诊治与研究

    通讯作者:

    李子坚 ldyy_lizj@lzu.edu.cn

Research on Bruton’s tyrosine kinase inhibitor for the treatment of primary immune-privileged site large B-cell lymphoma

More Information
  • 摘要: 原发免疫豁免部位大B细胞淋巴瘤(primary immune-privileged site large B-cell lymphoma,IP-DLBCLs)是世界卫生组织(WHO)淋巴样肿瘤分类第5版新的类别总称,指一组原发于免疫功能正常患者的免疫屏障之后部位的侵袭性B细胞淋巴瘤,起源于各自的解剖结构(如血脑、血网膜和血睾丸屏障)和各自原发部位的免疫调节系统所形成的免疫庇护所,并具有相同的免疫表型和分子特征,目前包括原发性中枢神经系统大B细胞淋巴瘤(primary central nervous system lymphoma,PCNSL)、原发睾丸大B细胞淋巴瘤(primary testicular large B-cell lymphoma,PTL)和原发玻璃体视网膜大B细胞淋巴瘤(primary vitreoretinal large B-cell lymphoma,PVRL)。该类疾病预后相对较差,目前尚无标准的治疗方案。Toll样受体(TLR)信号(通过MYD88突变)和B细胞受体(BCR)信号(通过CD79B突变)通路介导的NF-κB激活是三者发病的核心机制。该共同属性为这一类疾病的治疗提供了通用的靶点。BTK(Bruton's tyrosine kinase,BTK)是上述信号通路的中心分子。因此,BTK抑制剂可能是这类疾病合理的治疗药物选择。本文将就BTK抑制剂治疗原发免疫豁免部位大B细胞淋巴瘤的作用机制、临床研究、不良反应及耐药问题进行综述。

     

  • 表  1  5种BTK抑制剂疗效和常见不良反应总结

    参考文献 类型 治疗方案 例数(例) 疗效 不良反应
    ORR(%) mPFS(月) mOS(月)
    Grommes等[9] PCNSL 伊布替尼560~840 mg 13 77.0 4.60 15.0 3/4级淋巴细胞减少症(20%)、3/4级中性粒细胞减少症(15%)、3/4级高血糖症(15%)、3/4级血小板减少症(10%)
    Grommes等[10] R/R PCNSL 伊布替尼560~840 mg 29 81.0 4.00 19.5 3/4级淋巴细胞减少症(14%)、3/4级中性粒细胞减少症(11%)、3/4级ALT升高(9%)、3/4级高血糖症(7%)、
    3/4级血小板减少症(5%)
    Soussain[11] R/R PCNSL或PVSL 伊布替尼560~840 mg 52 52.0 4.80 19.2 2例眼前房出血、2例心房颤动、2例肺曲霉病
    Choquet[18] R/R PCNSL和PVRL 伊布替尼 18 56.0 1例肺曲霉病
    Grommes等[12] PCNSL 伊布替尼+HD-MTX+利妥昔单抗 9 89.0 9.20 未达到 3/4级淋巴细胞减少症(60%)、3/4级肺部感染(20%)、
    3/4级血小板减少(7%)、3/4级高血糖(7%)
    Grommes等[13] R/R PCNSL 伊布替尼+copanlisib 6 67.0
    Grommes等[14] R/R PCNSL和SCNSL 伊布替尼+利妥昔单抗+来那度胺 15 73.0 3.03 未达到 淋巴细胞减少症(20%)、皮疹(20%)
    Lionakis等[15] R/R PCNSL DA-TEDDi-R 18 86.0 15.30 未达到 4级中性粒细胞减少症(94%),4级血小板减少症(56%),
    肺部感染(50%),曲霉菌病(39%)
    Mark等[16] R/R PCNSL TEDDI-R 13 75.0 未达到 未达到 3/4级中性粒细胞减少症(83%)、3/4级血小板减少症(30%)
    Renaud等[17] R/R PCNSL 伊布替尼+替莫唑胺 22 55.0 11.70 8.9 感染(18%)
    Zhang等[19] R/R PCNSL 泽布替尼 8 81.8 3/4级中性粒细胞减少(69%)、3/4级血小板减少症(31%)、
    感染(31%)
    Song等[20] PCNSL RLZT±MTX 24 79.2 未达到 未达到 ≥3级血小板减少症(4%)、≥3级白细胞减少症(4%)
    Lin等[21] R/R PCNSL 泽布替尼+阿糖胞苷 12 75.0 5.60 未达到 4级血小板减少症(25%)
    Narita等[23] R/R PCNSL 替拉替尼 44 64.0 2.90 未达到 3/4级中性粒细胞减少症(9%),3/4级淋巴细胞减少症(7%),3/4级高血糖症(4.5%),3/4ALT升高(4.5%)
    Kawasaki等[24] R/R PCNSL 替拉替尼 140 63.0 ≥3级皮肤相关不良反应(5%)、≥3级感染(3.6%)
    Wu等[25] PCNSL 奥布替尼 23 100 未达到 未达到 血小板减少症(52%),白细胞减少(52%),皮疹(4%)
    Yang等[26] R/R PCNSL 奥布替尼+利妥昔单抗+HD-MTX+替莫唑胺+来那度胺 15 86.7 9.80 未达到 转氨酶升高(66.7%)、白细胞减少(26.7%)
    Ma等[27] PCNSL 奥布替尼+HD-MTX+利妥昔单抗 10 100 未达到 未达到 3级中性粒细胞减少症(30%)、
    3级淋巴细胞减少症(10%)
    Zeng等[28] PCNSL TOM±R 13 92.3 未达到 未达到 3/4 级白细胞减少(23.1%)、3/4级血小板减少症(7.7%)、
    3/4级发热(7.7%)和3/4级肺炎 (7.7%)
    Zhao等[29] PCNSL 奥布替尼+利妥昔单抗+HD-MTX 34 94.4 未达到 未达到 白细胞减少(8.8%)
    Zhang等[30] PCNSL 奥布替尼+抗PD-1抗体+福莫司汀 8 88.9 未达到 未达到 间质性肺炎(8%)
    NCT04688151 R/R PCNSL或SCNSL RAD 22
    NCT04906902 R/R PCNSL或SCNSL 阿卡替尼 15~21
    NCT04548648 PCNSL 阿卡替尼 16
    —:表示该研究未统计mPFS和OS
    下载: 导出CSV
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出版历程
  • 收稿日期:  2023-10-16
  • 录用日期:  2023-12-20
  • 修回日期:  2023-12-19

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