Second Tyrosine Kinase Inhibitor Discontinuation Attempt in Patients With Chronic Myeloid Leukemia
Second Tyrosine Kinase Inhibitor Discontinuation Attempt in Patients With Chronic Myeloid Leukemia
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DOI：
10.1002/cncr.30885
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发表时间：
2017-11-15
期刊：
影响因子：
6.2
通讯作者：
Mahon, Francois-Xavier
中科院分区：
文献类型：
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作者：
Legros, Laurence;Nicolini, Franck E.;Mahon, Francois-Xavier
背景：多项研究表明，接受酪氨酸激酶抑制剂(TKIs)治疗并达到并维持深分子应答(DMR)的慢性髓系白血病(CML)患者中，约有一半能够成功停止治疗。在分子复发的患者中，DMR在重新开始治疗后很快就会恢复。方法：作者报道了来自法国的一项观察性多中心研究RE-STIM的结果，该研究评估了70名在第一次尝试失败后再次尝试TKI的患者的免治疗缓解(TFR)。在第二次TKI尝试停止治疗后，重新引入治疗的触发因素是所有患者失去了主要的分子反应。结果：中位随访期为38.3个月(4.7-117个月)，45例(64.3%)患者在中位停药时间5.3个月(2-42个月)后失去了主要的分子反应。12、24、36个月的TFR发生率分别为48%(95%可信区间，37.6%~61.5%)、42%(95%可信区间，31.5%~55.4%)和35%(95%可信区间，24.4%~49.4%)。没有进展到晚期CML，也没有观察到TKI重新引入时的疗效问题。在单变量分析中，首次TKI尝试后分子复发的速度是唯一与预后显著相关的因素。首次TKI停用后3个月内仍留在DMR的患者24个月TFR率为72%(95%CI，48.8%~100%)，其他患者为36%(95%CI，25.8%~51.3%)。结论：这项研究首次证明第二次TKI终止尝试是安全的，第一次失败的TKI尝试并不排除第二次成功尝试。(C)2017年美国癌症协会。
BACKGROUND: Several studies have demonstrated that approximately one-half of patients with chronic myeloid leukemia (CML) who receive treatment with tyrosine kinase inhibitors (TKIs) and achieve and maintain a deep molecular response (DMR) are able to successfully discontinue therapy. In patients who have a molecular relapse, a DMR is rapidly regained upon treatment re-initiation. METHODS: The authors report the results from RE-STIM, a French observational, multicenter study that evaluated treatment-free remission (TFR) in 70 patients who re-attempted TKI discontinuation after a first unsuccessful attempt. After the second TKI discontinuation attempt, the trigger for treatment re-introduction was the loss of a major molecular response in all patients. RESULTS: The median follow-up was 38.3 months (range, 4.7-117 months), and 45 patients (64.3%) lost a major molecular response after a median time off therapy of 5.3 months (range, 2-42 months). TFR rates at 12, 24, and 36 months were 48% (95% confidence interval [CI], 37.6%-61.5%), 42% (95% CI, 31.5%-55.4%), and 35% (95% CI, 24.4%-49.4%), respectively. No progression toward advanced-phase CML occurred, and no efficacy issue was observed upon TKI re-introduction. In univariate analysis, the speed of molecular relapse after the first TKI discontinuation attempt was the only factor significantly associated with outcome. The TFR rate at 24 months was 72% (95% CI, 48.8%-100%) in patients who remained in DMR within the first 3 months after the first TKI discontinuation and 36% (95% CI, 25.8%-51.3%) for others. CONCLUSIONS: This study is the first to demonstrate that a second TKI discontinuation attempt is safe and that a first failed attempt at discontinuing TKI does not preclude a second successful attempt. (c) 2017 American Cancer Society.