在ASC4MORE研究中，对伊马替尼不耐受的患者加用阿伐替尼进行后续治疗，结果显示持续治疗率高且分子学缓解程度深，且随访期延长。
Asciminib add-on to imatinib demonstrates sustained high rates of ongoing therapy and deep molecular responses with prolonged follow-up in the ASC4MORE study.
作者信息
Hughes Timothy P, Saglio Giuseppe, Geissler Jan, Kim Dong-Wook, Lomaia Elza, Mayer Jiri, Turkina Anna, Kapoor Shruti, Cardoso Ana Paula, Nieman Becki, Quenet Sara, Cortes Jorge E
机构信息
South Australian Health and Medical Research Institute and University of Adelaide, Adelaide, SA, Australia.
Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
出版信息
J Hematol Oncol. 2024 Dec 18;17(1):125. doi: 10.1186/s13045-024-01642-6.
BACKGROUND
Up to 65% of patients with chronic myeloid leukemia (CML) who are treated with imatinib do not achieve sustained deep molecular response, which is required to attempt treatment-free remission. Asciminib is the only approved BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket. This unique mechanism of action allows asciminib to be combined with adenosine triphosphate-competitive tyrosine kinase inhibitors to prevent resistance and enhance efficacy. The phase II ASC4MORE trial investigated the strategy of adding asciminib to imatinib in patients who have not achieved deep molecular response with imatinib.
METHODS
In ASC4MORE, 84 patients with CML in chronic phase not achieving deep molecular response after ≥ 1 year of imatinib therapy were randomized to asciminib 40 or 60 mg once daily (QD) add-on to imatinib 400 mg QD, continued imatinib 400 mg QD, or switch to nilotinib 300 mg twice daily.
RESULTS
More patients in the asciminib 40- and 60-mg QD add-on arms (19.0% and 28.6%, respectively) achieved MR (BCR::ABL1 ≤ 0.0032% on the International Scale) at week 48 (primary endpoint) than patients in the continued imatinib (0.0%) and switch to nilotinib (4.8%) arms. Fewer patients discontinued asciminib 40- and 60-mg QD add-on treatment (14.3% and 23.8%, respectively) than imatinib (76.2%, including crossover patients) and nilotinib (47.6%). Asciminib add-on was tolerable, with rates of AEs and AEs leading to discontinuation less than those with nilotinib, although higher than those with continued imatinib (as expected in these patients who had already been tolerating imatinib for ≥ 1 year). No new or worsening safety signals were observed with asciminib add-on vs the known asciminib monotherapy safety profile.
CONCLUSIONS
Overall, these results support asciminib add-on as a treatment strategy to help patients with CML in chronic phase stay on therapy to safely achieve rapid and deep response, although further investigation is needed before this strategy is incorporated into clinical practice.
TRIAL REGISTRATION
NCT03578367.
背景
接受伊马替尼治疗的慢性髓性白血病（CML）患者中，高达65%未实现持续深度分子反应，而这是尝试无治疗缓解所必需的。阿塞西尼布是唯一获批的特异性靶向ABL肉豆蔻酰口袋的BCR::ABL1抑制剂。这种独特的作用机制使阿塞西尼布能够与三磷酸腺苷竞争性酪氨酸激酶抑制剂联合使用，以预防耐药并提高疗效。II期ASC4MORE试验研究了在未通过伊马替尼实现深度分子反应的患者中，将阿塞西尼布添加到伊马替尼治疗方案中的策略。
方法
在ASC4MORE试验中，84例慢性期CML患者在接受≥1年伊马替尼治疗后未实现深度分子反应，被随机分为三组：一组接受阿塞西尼布40或60mg每日一次（QD）联合伊马替尼400mg QD治疗，一组继续接受伊马替尼400mg QD治疗，另一组换用尼罗替尼300mg每日两次治疗。
结果
在第48周（主要终点）时，阿塞西尼布40mg QD联合治疗组和60mg QD联合治疗组中达到主要分子学缓解（国际量表上BCR::ABL1≤0.0032%）的患者比例分别为19.0%和28.6%，高于继续接受伊马替尼治疗组（0.0%）和换用尼罗替尼治疗组（4.8%）。与伊马替尼组（76.2%，包括交叉患者）和尼罗替尼组（47.6%）相比，停止阿塞西尼布40mg QD和60mg QD联合治疗的患者较少（分别为14.3%和23.8%）。添加阿塞西尼布是可耐受的，不良事件（AE）发生率和导致停药的AE发生率低于尼罗替尼组，尽管高于继续接受伊马替尼治疗组（对于这些已经耐受伊马替尼≥1年的患者，这是预期的）。与已知的阿塞西尼布单药治疗安全性概况相比，添加阿塞西尼布未观察到新的或更严重的安全信号。
结论
总体而言，这些结果支持添加阿塞西尼布作为一种治疗策略，以帮助慢性期CML患者持续接受治疗，安全地实现快速和深度反应，不过在将该策略纳入临床实践之前还需要进一步研究。
试验注册号
NCT03578367
Zotero 插件