Four BCR–ABL1 tyrosine-kinase inhibitors (TKIs) are approved for patients with newly diagnosed chronic myeloid leukaemia (CML): the first-generation agent imatinib and three second-generation TKIs, which have greater efficacy but also higher toxicity relative to imatinib. Now, results from the phase III ASC4FIRST trial reveal favourable outcomes in this setting with asciminib, an allosteric BCR–ABL1 TKI that specifically targets the ABL myristoyl pocket as opposed to being ATP competitive.

Patients were randomly allocated to receive asciminib (n = 201) or investigator’s choice of imatinib (n = 102) or a second-generation BCR–ABL1 TKI (n = 102). Major molecular response (MMR; defined as BCR-ABL1 transcript levels of ≤0.1%) at week 48 with asciminib versus all other TKIs and with asciminib versus imatinib were co-primary end points. MMR at week 48 with asciminib versus second-generation TKIs was a secondary end point.

四种 BCR-ABL1 酪氨酸激酶抑制剂 （TKI） 被批准用于新诊断的慢性粒细胞白血病 （CML） 患者：第一代药物伊马替尼和三种第二代 TKI，相对于伊马替尼，它们具有更高的疗效，但也具有更高的毒性。现在，III 期 ASC4FIRST 试验的结果显示，asciminib 在这种情况下取得了良好的结果，asciminib 是一种变构 BCR-ABL1 TKI，专门针对 ABL 肉豆蔻酰口袋，而不是 ATP 竞争性。

患者被随机分配接受 asciminib （n = 201） 或研究者选择的伊马替尼 （n = 102） 或第二代 BCR-ABL1 TKI （n = 102）。第 48 周时，asciminib 与所有其他 TKI 以及 asciminib 与伊马替尼相比的主要分子反应 （MMR;定义为 BCR-ABL1 转录水平为 ≤0.1%）是共同主要终点。与第二代 TKI 相比，asciminib 在第 48 周的 MMR 是次要终点。