The evolving use of measurable residual disease in chronic lymphocytic leukemia clinical trials.
The evolving use of measurable residual disease in chronic lymphocytic leukemia clinical trials.
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DOI：
10.3389/fonc.2023.1130617
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发表时间：
2023
影响因子：
4.7
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慢性淋巴细胞白血病（CLL）治疗时和治疗后评估的可测量残留疾病（MRD）状态与无进展和总生存期获益增加相关。最近，MRD评估已被纳入大型临床试验作为主要结局，并越来越多地用于常规实践中作为预后工具，治疗目标和早期干预的潜在触发因素。CLL的现代治疗提供了延长的缓解，导致传统试验结果的读出，如无进展和总生存期固有地延迟。这代表了将新药快速并入整体治疗设备的障碍。MRD提供了一个动态和强大的平台，用于评估慢性淋巴细胞白血病的治疗效果，补充传统的结果措施，并加快获得新药。在这里，我们提供了一个CLL治疗的最新主要临床试验的全面审查，重点是小分子抑制剂和单克隆抗体组合，最近出现的标准一线和复发治疗方案。我们探讨了MRD（包括新技术）的评估和报告以及标准化的挑战，并对MRD作为临床试验终点的相关性和充分性进行了全面审查。我们进一步讨论了MRD数据对临床决策的影响，以及它如何影响患者的体验。最后，我们评估即将到来的试验设计和临床实践是如何在面对MRD驱动的结果。
Measurable residual disease (MRD) status in chronic lymphocytic leukemia (CLL), assessed on and after treatment, correlates with increased progression-free and overall survival benefit. More recently, MRD assessment has been included in large clinical trials as a primary outcome and is increasingly used in routine practice as a prognostic tool, a therapeutic goal, and potentially a trigger for early intervention. Modern therapy for CLL delivers prolonged remissions, causing readout of traditional trial outcomes such as progression-free and overall survival to be inherently delayed. This represents a barrier for the rapid incorporation of novel drugs to the overall therapeutic armamentarium. MRD offers a dynamic and robust platform for the assessment of treatment efficacy in CLL, complementing traditional outcome measures and accelerating access to novel drugs. Here, we provide a comprehensive review of recent major clinical trials of CLL therapy, focusing on small-molecule inhibitors and monoclonal antibody combinations that have recently emerged as the standard frontline and relapse treatment options. We explore the assessment and reporting of MRD (including novel techniques) and the challenges of standardization and provide a comprehensive review of the relevance and adequacy of MRD as a clinical trial endpoint. We further discuss the impact that MRD data have on clinical decision-making and how it can influence a patient’s experience. Finally, we evaluate how upcoming trial design and clinical practice are evolving in the face of MRD-driven outcomes.
影响因子：
6.5
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