文章：

慢性淋巴细胞白血病治疗反应与耐药性监测

Monitoring Response and Resistance to Treatment in Chronic Lymphocytic Leukemia

原文发布日期：28 May 2024

DOI: 10.3390/cancers16112049

类型: Article

开放获取: 是

英文摘要：

The recent evolution in chronic lymphocytic leukemia (CLL) targeted therapies led to a progressive change in the way clinicians manage the goals of treatment and evaluate the response to treatment in respect to the paradigm of the chemoimmunotherapy era. Continuous therapies with BTK inhibitors achieve prolonged and sustained control of the disease. On the other hand, venetoclax and anti-CD20 monoclonal antibodies or, more recently, ibrutinib plus venetoclax combinations, given for a fixed duration, achieve undetectable measurable residual disease (uMRD) in the vast majority of patients. On these grounds, a time-limited MRD-driven strategy, a previously unexplored scenario in CLL, is being attempted. On the other side of the spectrum, novel genetic and non-genetic mechanisms of resistance to targeted treatments are emerging. Here we review the response assessment criteria, the evolution and clinical application of MRD analysis and the mechanisms of resistance according to the novel treatment strategies within clinical trials. The extent to which this novel evidence will translate in the real-life management of CLL patients remains an open issue to be addressed.

摘要翻译： 

慢性淋巴细胞白血病（CLL）靶向治疗的最新进展，促使临床医生在治疗目标设定及疗效评估方式上逐步改变，这与化学免疫治疗时代的范式形成对比。布鲁顿酪氨酸激酶（BTK）抑制剂的持续治疗可实现疾病的长期稳定控制。另一方面，固定疗程的维奈托克联合抗CD20单克隆抗体疗法，以及近期出现的伊布替尼联合维奈托克方案，能使绝大多数患者达到不可检测的微小残留病（uMRD）状态。基于此，一种以MRD为导向的限时治疗策略——这一CLL治疗领域前所未有的新模式——正在探索中。与此同时，针对靶向治疗的新型遗传与非遗传耐药机制逐渐显现。本文系统综述了临床试验中新型治疗策略下的疗效评估标准、MRD分析的进展与临床应用以及耐药机制。这些新证据将在多大程度上转化为临床实践中CLL患者的实际管理策略，仍是亟待解决的重要课题。

原文链接：

Monitoring Response and Resistance to Treatment in Chronic Lymphocytic Leukemia