Asciminib for Philadelphia chromosome-positive leukemias.

Despite the development of second- and third-generation tyrosine kinase inhibitors (TKI), their impact has been incremental in improving outcomes for CML patients.

尽管开发了第二代和第三代酪氨酸激酶抑制剂（TKI），但它们对改善CML患者预后的影响力是逐步的。

While frontline use of second-generation TKI has improved molecular response rates and reduced progression to blast phase, there has been no improvement in overall survivalcompared to that achieved with imatinib, likely due to the higher toxicity and consequent higher non-CML-related mortality.

尽管第二代酪氨酸激酶抑制剂(TKI)作为一线治疗提高了分子反应率并减少了向急变期的进展，但与伊马替尼相比，总生存并未得到改善，这可能是由于其更高的毒性以及随之而来的非慢性髓性白血病(CML)相关死亡率较高。

Imatinib remains the most prescribed therapy for CML worldwide, despite it being the least potent TKI and most prone to resistance and progression.

尽管伊马替尼是效力最低、最易产生耐药性和进展的TKI，但它仍然是全球治疗CML最常用的疗法。

Asciminib, the first STAMP (specifically targeting the ABL myristoyl pocket) inhibitor, binds to the myristoyl pocket of BCR::ABL1.

Asciminib是首个STAMP（特异性靶向ABL肉豆蔻酰口袋）抑制剂，它与BCR::ABL1的肉豆蔻酰口袋结合。

Its specificity minimizes off-target toxicity which enabes asciminib to finally break this frustrating link between potency and toxicity.

其特异性最小化了非靶向毒性，这使得Asciminib最终打破了效力与毒性之间的这种令人沮丧的联系。

After a decade of clinical trials, both in patients with resistance and intolerance to two or more TKI, and more recently in the frontline setting, asciminib is fulfilling its early promise of a more rapid and reliable pathway to long-term disease control with minimal toxicity.

经过十年的临床试验，无论是在对两种或更多TKI产生耐药性和不耐受的患者中，还是最近在一线治疗环境中，asciminib都在实现其早期承诺，即通过更快速、更可靠的途径实现长期疾病控制，并且毒性最小。

There are, however, some unexpected challenges when using asciminib that require further investigation.

然而，在使用asciminib时，也出现了一些需要进一步研究的意外挑战。

In this Spotlight Review we examine the key studies and outline the potential impact and current limitations of this first STAMP inhibitor in the CML setting and in other leukemias in which ABL1 or ABL2 is the key target.

在这篇焦点综述中，我们将审视关键研究，并概述这种首个STAMP抑制剂在慢性髓性白血病（CML）环境以及在ABL1或ABL2作为关键靶点的其他白血病中的潜在影响和当前局限性。