Mauro Michael J, Minami Yosuke, Hochhaus Andreas, Lomaia Elza, Voloshin Sergey, Turkina Anna, Kim Dong-Wook, Apperley Jane F, Cortes Jorge E, Abdo Andre, Fogliatto Laura Maria, Kim Dennis Dong Hwan, le Coutre Philipp, Saussele Susanne, Annunziata Mario, Hughes Timothy P, Chaudhri Naeem, Chee Lynette, García-Gutiérrez Valentin, Sasaki Koji, Boquimpani Carla, Kapoor Shruti, Espurz Noemi, Dhamal Vishal, Rea Delphine
Chronic Myeloid Leukemia Program, Memorial Sloan Kettering Cancer Center, New York, NY.
Department of Hematology, National Cancer Center Hospital East, Kashiwa, Japan.
Blood Adv. 2025 Aug 26;9(16):4248-4259. doi: 10.1182/bloodadvances.2025016042.
The efficacy of and disease control afforded by tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia in chronic phase (CML-CP) have led to increased longevity and thus the continued pursuit of alternative therapies that are efficacious and maximize tolerability. The 24- and 96-week analyses from ASCEMBL demonstrated superior efficacy, safety, and tolerability of asciminib when compared with bosutinib in later-line therapy, thereby meeting the primary and key secondary objectives. With nearly 4 years of follow-up, data from ASCEMBL continued to demonstrate the superior efficacy, safety, and tolerability of asciminib over bosutinib. At week 156, the major molecular response (MMR) rates remained higher with asciminib (33.8%) than with bosutinib (10.5%); the difference in MMR rates between arms, after adjusting for baseline major cytogenetic response, was 23.2% (95% confidence interval, 13.14-33.18; 2-sided P < .001). Asciminib continued to cause fewer grade ≥3 adverse events (AEs; 59.6% vs 68.4%) and fewer AEs that led to treatment discontinuation (8.3% vs 27.6%) than bosutinib. This updated analysis also includes patients who switched to asciminib because of a lack of efficacy with bosutinib. Two of the 25 patients who switched achieved MMR by the end of study, suggesting that earlier incorporation of asciminib, before other TKIs, may improve responses, albeit modestly. These long-term results further solidify asciminib as the therapy of choice for patients with CML-CP who were previously treated with ≥2 previous TKIs. This trial was registered at clinicaltrials.gov as #NCT03106779.
酪氨酸激酶抑制剂(TKIs)在慢性期慢性髓性白血病(CML-CP)中的疗效及疾病控制效果使患者寿命延长,因此人们持续寻求疗效显著且耐受性最佳的替代疗法。ASCEMBL研究的24周和96周分析表明,在后续治疗中,与博舒替尼相比,阿塞西尼布具有更优的疗效、安全性和耐受性,从而实现了主要和关键次要目标。经过近4年的随访,ASCEMBL研究数据继续证明阿塞西尼布在疗效、安全性和耐受性方面优于博舒替尼。在第156周时,阿塞西尼布组的主要分子反应(MMR)率(33.8%)仍高于博舒替尼组(10.5%);在调整基线主要细胞遗传学反应后,两组MMR率的差异为23.2%(95%置信区间为13.14 - 33.18;双侧P < 0.001)。与博舒替尼相比,阿塞西尼布导致的≥3级不良事件(AEs)更少(59.6%对68.4%),因AE导致治疗中断的情况也更少(8.3%对27.6%)。此次更新分析还纳入了因博舒替尼疗效不佳而改用阿塞西尼布的患者。在改用阿塞西尼布的25例患者中,有2例在研究结束时达到MMR,这表明在使用其他TKIs之前更早使用阿塞西尼布可能会改善反应,尽管改善程度不大。这些长期结果进一步巩固了阿塞西尼布作为先前接受过≥2种TKIs治疗的CML-CP患者首选治疗方案的地位。该试验已在clinicaltrials.gov上注册,编号为#NCT03106779。