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 Most common reasons for treatment discontinuation were adverse events (6%), loss of response (4%), and withdrawn consent (5%).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.

摘要 阿西米尼是一种肉豆蔻酰位点BCR::ABL1抑制剂，被批准用于既往接受过≥2种治疗方案失败的慢性期慢性髓性白血病（CP - CML）患者。澳大利亚白血病和淋巴瘤小组开展了新诊断CML中的阿西米尼评估研究，以评估阿西米尼对新诊断CP - CML的疗效。患者开始接受阿西米尼40mg，每日两次。治疗失败定义为在3个月或6个月时BCR::ABL1＞10%，或在12个月或18个月时＞1%，这些患者除阿西米尼外还接受伊马替尼、尼洛替尼或达沙替尼治疗。对于疗效欠佳的患者，定义为在6个月时水平为1% - 10%，在12个月时＞0.1% - 1%，或在18个月时＞0.01% - 1%，阿西米尼剂量增加至80mg，每日两次。中位随访21个月（范围0 - 36个月），101例患者中有82例继续使用阿西米尼。治疗终止的最常见原因是不良事件（6%）、疗效丧失（4%）和撤回同意（5%）。无死亡病例；1例患者发生淋巴细胞白血病急变。共同主要终点是早期分子学反应（3个月时BCR::ABL1≤10%），达到93%（96%置信区间[CI]，86 - 97%），以及12个月时的主要分子学反应达到79%；（95%CI，70 - 87%）。24个月时分子学反应4.5的累积发生率为53%。1例患者发生2次脑血管事件；未报告其他动脉闭塞事件。阿西米尼作为慢性髓性白血病慢性期的一线治疗可导致较高的分子学反应率，耐受性良好，因毒性而停药的比率较低。该试验在https://www.anzctr.org.au/注册，注册号为#ACTRN12620000851965。