PDF(Pubmed)
Abstract：
To assess the impact of first-line treatment with targeted agents (TAs) or fludarabine, cyclophosphamide, and rituximab (FCR)-based chemo-immunotherapy (CIT) on overall survival (OS) compared to age- and sex-matched individuals in the general population, we conducted an aggregated analysis of phase 3 clinical trials, including the two FLAIR sub-studies, ECOG1912, and CLL13 trials. The restricted mean survival time (RMST), an alternative measure in outcome analyses capturing OS changes over the entire history of the disease, was used to minimize biases associated with the short follow-up time of trials. Patients treated with TAs demonstrated a higher 5-year RMST (58.1 months; 95% CI: 57.4 to 58.8) compared to those treated with CIT (5-year RMST, 56.9 months; 95% CI: 56.7-58.2). Furthermore, the OS comparison of treatment groups with the AGMGP suggests that TAs may mitigate the impact of CLL on OS during the first five years post-treatment initiation. In summary, the 5-year RMST difference was -0.4 months (95% CI: -0.8 to 0.2; p = 0.10) when comparing CLL patients treated with TAs to the Italian age- and gender-matched general population (AGMGP). A similar trend was observed when CLL patients treated with TAs were compared to the US AGMGP (5-year RMST difference, 0.3 months; 95% CI: -0.1 to 0.9; p = 0.12). In contrast, CLL patients treated with FCR exhibited sustained OS differences when compared to both the Italian cohort (5-year RMST difference: -1.6 months; 95% CI: -2.4 to -0.9; p < 0.0001) and the US AGMGP cohort (5-year RMST difference: -0.9 months; 95% CI: -1.7 to -0.2; p = 0.015). Although these results support TAs as the preferred first-line treatment for younger CLL patients, it is crucial to acknowledge that variations in patient selection criteria and clinical profiles across clinical trials necessitate a cautious interpretation of these findings that should be viewed as directional and hypothesis-generating. A longer follow-up is needed to assess the survival improvement of younger CLL patients treated with TAs relative to the AGMGP.
摘要：
为了评估一线靶向药物（TA）或氟达拉滨治疗的影响，环磷酰胺,和基于利妥昔单抗（FCR）的化学免疫疗法（CIT）与普通人群中年龄和性别匹配的个体相比，我们对3期临床试验进行了综合分析，包括两个FLAIR子研究，ECOG1912和CLL13试验。受限平均生存时间(RMST)，结果分析中的另一种测量方法是捕获整个疾病史的OS变化，用于最大限度地减少与短随访时间的试验相关的偏见。与接受CIT（5年RMST，56.9个月；95%CI：56.7-58.2）。此外，治疗组与AGMGP的OS比较表明,在治疗开始后的前5年内,TA可能减轻CLL对OS的影响.总之,将接受TAs治疗的CLL患者与意大利年龄和性别匹配的一般人群(AGMGP)进行比较,5年RMST差异为-0.4个月(95%CI:-0.8~0.2;p=0.10).当将接受TA治疗的CLL患者与美国AGMGP进行比较时，观察到类似的趋势(5年RMST差异，0.3个月；95%CI：-0.1至0.9；p=0.12）。相比之下,与意大利队列（5年RMST差异：-1.6个月；95％CI：-2.4至-0.9；p<0.0001）和美国AGMGP队列（5年RMST差异：-0.9个月；95％CI：-1.7至-0.2；p=0.015）相比，接受FCR治疗的CLL患者表现出持续的OS差异。尽管这些结果支持TA作为年轻CLL患者的首选一线治疗，我们必须承认,临床试验中患者选择标准和临床概况的差异,需要对这些发现进行谨慎的解释,这些结果应被视为具有方向性和假设生成性.需要更长的随访时间来评估接受TA治疗的年轻CLL患者相对于AGMGP的生存改善。
