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Abstract：
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：
慢性淋巴细胞白血病（CLL）靶向治疗的最新发展导致临床医生管理治疗目标和评估化学免疫疗法时代范式对治疗反应的方式发生了逐步变化。BTK抑制剂的连续治疗可实现疾病的长期和持续控制。另一方面,维奈托克和抗CD20单克隆抗体或，最近,伊布替尼加维奈托克组合，给定固定的持续时间，在绝大多数患者中实现无法检测到的可测量残留疾病(uMRD)。基于这些理由,时间有限的MRD驱动战略，CLL中以前未探索的场景，正在尝试。在光谱的另一边，新的遗传和非遗传机制对靶向治疗的抗性正在出现。在这里，我们回顾了反应评估标准，根据临床试验中的新治疗策略，MRD分析的演变和临床应用以及耐药机制。这种新证据在CLL患者的现实生活管理中的转化程度仍然是一个有待解决的问题。
