Shacham-Abulafia Adi, Volcheck Yulia, Ellis Martin, Shapira Shirley, Tavor Sigal, Gourevitch Anna, Kreiniz Natalia, Stanevski Anfisa, Raanani Pia, Koren-Michowitz Maya
Davidoff Cancer Center, Rabin Medical Center, Institute of Hematology, Petah-Tikva, Israel.
School of Medicine, Faculty of Medicine and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
Eur J Haematol. 2025 Feb;114(2):258-263. doi: 10.1111/ejh.14330. Epub 2024 Oct 21.
Asciminib, a novel allosteric BCR::ABL1 inhibitor, targets the ABL1 myristoyl pocket to potentially reduce toxicity and enhance efficacy. It is approved for Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CML-CP) in patients with resistance or intolerance to two or more tyrosine kinase inhibitors (TKIs) or those with the T315I mutation.
This retrospective analysis evaluated patients with CML treated with asciminib under a managed-access program across eight Israeli centers from July 2019 to August 2022. We assessed treatment responses, toxicities, event-free survival (EFS), and overall survival (OS) using Kaplan-Meier methods.
The study included 30 patients who had received a median of three prior TKIs, with 73% starting asciminib due to intolerance. After a median follow-up of 7.1 months, 85% of those without prior complete cytogenetic response (CCyR) achieved CCyR, and 60% previously not in major molecular response (MMR) attained MMR. Resistance was rare (10%), with no cardiovascular events reported despite high baseline comorbidity (73%). Median EFS was 47 months; median OS was not reached.
Asciminib demonstrates significant efficacy and tolerability in heavily pretreated patients with CML-CP, with no new cardiovascular events observed. Further long-term studies are necessary to explore its full cardiovascular impact.
阿斯科利尼布是一种新型变构BCR::ABL1抑制剂，作用于ABL1肉豆蔻酰口袋，有可能降低毒性并提高疗效。它被批准用于对两种或更多种酪氨酸激酶抑制剂（TKIs）耐药或不耐受或存在T315I突变的费城染色体阳性慢性期慢性髓性白血病（CML-CP）患者。
这项回顾性分析评估了2019年7月至2022年8月期间在以色列8个中心的管理准入项目下接受阿斯科利尼布治疗的CML患者。我们使用Kaplan-Meier方法评估治疗反应、毒性、无事件生存期（EFS）和总生存期（OS）。
该研究纳入了30例患者，这些患者之前接受的TKIs中位数为3种，73%的患者因不耐受开始使用阿斯科利尼布。中位随访7.1个月后，85%之前未获得完全细胞遗传学缓解（CCyR）的患者实现了CCyR，60%之前未达到主要分子缓解（MMR）的患者达到了MMR。耐药情况罕见（10%），尽管基线合并症发生率高（73%），但未报告心血管事件。中位EFS为47个月；中位OS未达到。
阿斯科利尼布在接受过大量治疗的CML-CP患者中显示出显著的疗效和耐受性，未观察到新的心血管事件。需要进一步的长期研究来探讨其对心血管的全面影响。
