本文由小咖机器人翻译整理

期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2400858

摘要内容如下：

背景

初诊慢性粒细胞白血病（CML）患者需要长期高效安全的治疗。阿西替尼是一种特异性靶向ABL肉豆蔻酰口袋的BCR：:ABL1抑制剂，与目前可用的一线ATP竞争性酪氨酸激酶抑制剂（TKIs）相比，阿西替尼可能提供更好的疗效和安全性以及更少的副作用。

方法

在一项3期临床试验中，新诊断的CML患者以1:1的比例被随机分配接受阿西替尼（80 mg，每日一次）或研究者选择的TKI，根据欧洲治疗和结果研究长期生存评分类别（低、中或高风险）和研究者在随机前选择的TKI（包括伊马替尼和第二代TKI）进行随机分层。主要终点是第48周时的主要分子反应（定义为国际范围[IS]中BCR：:ABL1转录物水平≤0.1%），用于比较阿西替尼和研究者选择的TKIs之间以及随机前选择的伊马替尼层中的阿西替尼和研究者选择的TKIs之间。

结果

共有201名患者接受阿西替尼治疗，204名患者接受研究者选择的TKIs治疗。阿西替尼组的中位随访时间为16.3个月，研究者选择的TKI组的中位随访时间为15.7个月。在第48周，阿西替尼组67.7%的患者出现主要分子反应，而研究者选择的TKI组为49.0%（差异，18.9个百分点；95%置信区间[CI]，9.6至28.2；校正双侧P<0.001]），阿西替尼组中69.3%的患者与伊马替尼组中40.2%的患者在伊马替尼层中（差异，29.6个百分点；95%可信区间为16.9~42.2；调整后双侧P<0.001）。在第48周时，在第二代TKI层中，阿西替尼组和TKIs组主要分子应答的患者百分比分别为66.0%和57.8%（差异，8.2个百分点；95%置信区间，-5.1至21.5）。与伊马替尼（44.4%和11.1%）和第二代TKIs（54.9%和9.8%）相比，阿西替尼（分别为38.0%和4.5%）的3级或以上不良事件和导致试验方案中断的事件发生率较低。

结论

在该试验中，比较了阿西替尼与研究者选择的TKIs和伊马替尼，阿西替尼在新诊断的慢性期CML患者中显示出更好的疗效和良好的安全性。直接比较阿西替尼和第二代TKIs不是主要目的。（由诺华公司资助；ASC4First ClinicalTrials.gov编号，NCT04971226）。

英文原文如下：

Abstracts

BACKGROUND  Patients with newly diagnosed chronic myeloid leukemia (CML) need long-term therapy with high efficacy and safety. Asciminib, a BCR::ABL1 inhibitor specifically targeting the ABL myristoyl pocket, may offer better efficacy and safety and fewer side effects than currently available frontline ATP-competitive tyrosine kinase inhibitors (TKIs).

METHODS  In a phase 3 trial, patients with newly diagnosed CML were randomly assigned in a 1:1 ratio to receive either asciminib (80 mg once daily) or an investigator-selected TKI, with randomization stratified by European Treatment and Outcome Study long-term survival score category (low, intermediate, or high risk) and by TKI selected by investigators before randomization (including imatinib and second-generation TKIs). The primary end points were major molecular response (defined as BCR::ABL1 transcript levels ≤0.1% on the International Scale [IS]) at week 48, for comparisons between asciminib and investigator-selected TKIs and between asciminib and investigator-selected TKIs in the prerandomization-selected imatinib stratum.

RESULTS  A total of 201 patients were assigned to receive asciminib and 204 to receive investigator-selected TKIs. The median follow-up was 16.3 months in the asciminib group and 15.7 months in the investigator-selected TKI group. A major molecular response at week 48 occurred in 67.7% of patients in the asciminib group, as compared with 49.0% in the investigator-selected TKI group (difference, 18.9 percentage points; 95% confidence interval [CI], 9.6 to 28.2; adjusted two-sided P<0.001]), and in 69.3% of patients in the asciminib group as compared with 40.2% in the imatinib group within the imatinib stratum (difference, 29.6 percentage points; 95% CI, 16.9 to 42.2; adjusted two-sided P<0.001). The percentage of patients with a major molecular response at week 48 was 66.0% with asciminib and 57.8% with TKIs in the second-generation TKI stratum (difference, 8.2 percentage points; 95% CI, -5.1 to 21.5). Adverse events of grade 3 or higher and events leading to discontinuation of the trial regimen were less frequent with asciminib (38.0% and 4.5%, respectively) than with imatinib (44.4% and 11.1%) and second-generation TKIs (54.9% and 9.8%).

CONCLUSIONS  In this trial comparing asciminib with investigator-selected TKIs and imatinib, asciminib showed superior efficacy and a favorable safety profile in patients with newly diagnosed chronic-phase CML. Direct comparison between asciminib and second-generation TKIs was not a primary objective. (Funded by Novartis; ASC4FIRST ClinicalTrials.gov number, NCT04971226).

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