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新型靶向疗法治疗老年慢性淋巴细胞白血病:系统评价。

Novel Targeted Therapies for Chronic Lymphocytic Leukemia in Elderly Patients: A Systematic Review.

机构信息

Department of Internal Medicine, King Edward Medical University, Lahore, Pakistan.

Department of Internal Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan.

出版信息

Clin Lymphoma Myeloma Leuk. 2020 Jul;20(7):e414-e426. doi: 10.1016/j.clml.2020.02.013. Epub 2020 Feb 27.

Abstract

Chronic lymphocytic leukemia (CLL) typically affects older patients; administration of traditional cytotoxic therapies in old patients has very modest benefit with no survival improvement. With better understanding of CLL biology, trends are shifting towards the use of targeted therapies. The objective of this article is to review the safety and efficacy of various novel agents that specifically target the dysregulated pathways, with particular attention to elderly patients. Agents like B-cell receptor (BCR) inhibitors (Bruton's tyrosine kinase inhibitors [ibrutinib]), phosphatidylinositol 3-kinase inhibitors (idelalisib), spleen tyrosine kinase inhibitors (entospletinib), Bcl-2 inhibitors (venetoclax), immunomodulators (lenalidomide), and monoclonal antibodies (obinutuzumab, ofatumumab) have shown activity in CLL with a very favorable toxicity profile. Newer agents have improved clinical outcomes, and have tolerable toxicity profiles in elderly patients, resulting in the treatment with individualized therapy approach for CLL.

摘要

慢性淋巴细胞白血病(CLL)通常影响老年患者;在老年患者中使用传统细胞毒性疗法的获益非常有限,不能改善生存。随着对 CLL 生物学的更好理解,目前的趋势正在转向使用靶向治疗。本文的目的是综述各种新型靶向异常通路药物的安全性和疗效,特别关注老年患者。像 B 细胞受体(BCR)抑制剂(布鲁顿酪氨酸激酶抑制剂[依鲁替尼])、磷脂酰肌醇 3-激酶抑制剂(idelalisib)、脾酪氨酸激酶抑制剂(entospletinib)、Bcl-2 抑制剂(venetoclax)、免疫调节剂(来那度胺)和单克隆抗体(obinutuzumab、ofatumumab)在 CLL 中具有活性,且毒性谱非常有利。新型药物改善了临床结局,且在老年患者中具有可耐受的毒性谱,使个体化治疗方法在 CLL 治疗中成为可能。

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