Asciminib is approved for patients with Philadelphia chromosome–positive chronic-phase chronic myeloid leukemia (CML-CP) who received ≥2 prior tyrosine kinase inhibitors or have the T315I mutation. We report updated results of a phase 1, open-label, nonrandomized trial (NCT02081378) assessing the safety, tolerability, and antileukemic activity of asciminib monotherapy 10–200 mg once or twice daily in 115 patients with CML-CP without T315I (data cutoff: January 6, 2021). After ≈4-year median exposure, 69.6% of patients remained on asciminib. The most common grade ≥3 adverse events (AEs) included increased pancreatic enzymes (22.6%), thrombocytopenia (13.9%), hypertension (13.0%), and neutropenia (12.2%); all-grade AEs (mostly grade 1/2) included musculoskeletal pain (59.1%), upper respiratory tract infection (41.7%), and fatigue (40.9%). Clinical pancreatitis and arterial occlusive events (AOEs) occurred in 7.0% and 8.7%, respectively. Most AEs occurred during year 1; the subsequent likelihood of new events, including AOEs, was low. By data cutoff, among patients without the indicated response at baseline, 61.3% achieved BCR::ABL1 ≤ 1%, 61.6% achieved ≤0.1% (major molecular response [MMR]), and 33.7% achieved ≤0.01% on the International Scale. MMR was maintained in 48/53 patients who achieved it and 19/20 who were in MMR at screening, supporting the long-term safety and efficacy of asciminib in this population.

阿西米尼被批准用于治疗费城染色体阳性慢性期慢性粒细胞白血病 (CML-CP) 患者，这些患者既往接受过 ≥2 种酪氨酸激酶抑制剂或具有 T315I 突变。我们报告了一项 1 期、开放标签、非随机试验 (NCT02081378) 的最新结果，该试验评估了 115 名无 T315I 的 CML-CP 患者中阿西米尼单一疗法 10-200 mg 每天一次或两次的安全性、耐受性和抗白血病活性（数据截止：2021 年 1 月 6 日）。经过约 4 年的中位暴露后，69.6% 的患者仍继续服用阿西米尼。最常见的≥3级不良事件（AE）包括胰酶升高（22.6%）、血小板减少（13.9%）、高血压（13.0%）和中性粒细胞减少（12.2%）；所有级别的 AE（大部分为 1/2 级）包括肌肉骨骼疼痛（59.1%）、上呼吸道感染（41.7%）和疲劳（40.9%）。临床胰腺炎和动脉闭塞事件 (AOE) 的发生率分别为 7.0% 和 8.7%。大多数 AE 发生在第一年；随后发生新事件（包括 AOE）的可能性很低。截至数据截止，在基线时没有显示缓解的患者中，61.3% 的患者达到BCR::ABL1 ≤ 1%，61.6% 的患者达到 ≤0.1%（主要分子缓解 [MMR]），33.7% 的患者达到国际标准的 ≤0.01% 。 48/53 名达到 MMR 的患者维持了 MMR，19/20 名筛选时处于 MMR 的患者维持了 MMR，这支持了阿西米尼在该人群中的长期安全性和有效性。