阿西米尼单药作为慢性期慢性髓性白血病的一线治疗:ASCEND研究结果

IF 21 1区 医学 Q1 HEMATOLOGY
Blood Pub Date : 2024-11-07 DOI:10.1182/blood.2024024657
David T Yeung, Naranie Shanmuganathan, John Reynolds, Susan Branford, Mannu Walia, Agnes S M Yong, Jake Shortt, Lynette Chee, Nicholas Viiala, Ilona Cunningham, David M Ross, Alwyn D'Souza, Matthew Wright, Rosemary Harrup, Cecily Forsyth, Robin Filshie, Steven Lane, Peter Browett, Carolyn Grove, Andrew P Grigg, Timothy P Hughes
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引用次数: 0

摘要

Asciminib是一种肉豆蔻酰基位点BCR::ABL1抑制剂,已被批准用于既往接受过≥2种疗法的慢性期慢性髓性白血病(CP-CML)患者。澳大拉西亚白血病与淋巴瘤组织(ALLG)开展了 ASCEND 研究,以评估 asciminib 对新诊断的 CP-CML 的疗效。患者开始服用阿昔米尼 40 毫克,每天两次(BID),之后根据分子指标进行管理。治疗失败的患者(定义为 3 或 6 个月时 BCR::ABL1 >10% (IS),或 12 或 18 个月时 >1%)除接受阿昔米尼治疗外,还接受伊马替尼、尼洛替尼或达沙替尼治疗。对于反应不理想的患者,即6个月时反应水平为1%-10%、12个月时反应水平>0.1%-1%或18个月时反应水平>0.01%-1%的患者,阿昔米尼的剂量增加到80毫克,每日两次。中位随访 21 个月(0-36 个月),82/101 例患者继续服用阿昔米尼。最常见的治疗中止原因是不良事件(6%)、反应消失(4%)和撤回同意(5%)。无死亡病例;1 名患者在 6 个月时出现淋巴细胞凋亡危象。共同主要终点是早期分子反应(3个月时BCR::ABL1≤10%),93%的患者(96% CI 86-97%)实现了这一目标,12个月时主要分子反应的实现率分别为79%;(95% CI 69.7-86.8%)。到24个月时,MR4.5的累积发生率为53%。一名患者发生了2次脑血管事件;未报告其他动脉闭塞事件。阿西米尼作为CP-CML的一线疗法,分子反应率高,耐受性好,因毒性停药率低。(澳新临床试验注册中心 ACTRN12620000851965)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Asciminib monotherapy as frontline treatment of chronic-phase chronic myeloid leukemia: results from the ASCEND study.

Abstract: Asciminib is a myristoyl site BCR::ABL1 inhibitor approved for patients with chronic-phase chronic myeloid leukemia (CP-CML) failing ≥2 prior lines of therapy. The Australasian Leukaemia and Lymphoma Group conducted the Asciminib Evaluation in Newly Diagnosed CML study to assess efficacy of asciminib for newly diagnosed CP-CML. Patients commenced asciminib 40 mg twice daily. Patients with treatment failure, defined as BCR::ABL1 of >10% at 3 or 6 months, or >1% at 12 or 18 months, received either imatinib, nilotinib, or dasatinib in addition to asciminib. In patients with suboptimal response, defined as levels of 1% to 10% at 6 months, >0.1% to 1% at 12 months, or >0.01% to 1% at 18 months, the asciminib dose was increased to 80 mg twice daily. With a median follow-up of 21 months (range, 0-36), 82 of 101 patients continue asciminib. Most common reasons for treatment discontinuation were adverse events (6%), loss of response (4%), and withdrawn consent (5%). There were no deaths; 1 patient developed lymphoid blast crisis. The coprimary end points were early molecular response (BCR::ABL1 of ≤10% at 3 months), achieved in 93% (96% confidence interval [CI], 86-97%), and major molecular response by 12 months achieved in 79%; (95% CI, 70-87%), respectively. Cumulative incidence of molecular response 4.5 was 53% by 24 months. One patient had 2 cerebrovascular events; no other arterial occlusive events were reported. Asciminib as frontline CP-CML therapy leads to high rates of molecular response with excellent tolerance and a low rate of discontinuation for toxicity. This trial was registered at https://www.anzctr.org.au/ as #ACTRN12620000851965.

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来源期刊
Blood
Blood 医学-血液学
CiteScore
23.60
自引率
3.90%
发文量
955
审稿时长
1 months
期刊介绍: Blood, the official journal of the American Society of Hematology, published online and in print, provides an international forum for the publication of original articles describing basic laboratory, translational, and clinical investigations in hematology. Primary research articles will be published under the following scientific categories: Clinical Trials and Observations; Gene Therapy; Hematopoiesis and Stem Cells; Immunobiology and Immunotherapy scope; Myeloid Neoplasia; Lymphoid Neoplasia; Phagocytes, Granulocytes and Myelopoiesis; Platelets and Thrombopoiesis; Red Cells, Iron and Erythropoiesis; Thrombosis and Hemostasis; Transfusion Medicine; Transplantation; and Vascular Biology. Papers can be listed under more than one category as appropriate.
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