评价残留疾病和 TKI 持续时间是伊马替尼一线治疗慢性期 CML 患者停药后分子复发的关键预测因素。
Evaluation of Residual Disease and TKI Duration Are Critical Predictive Factors for Molecular Recurrence after Stopping Imatinib First-line in Chronic Phase CML Patients.
机构信息
Department of Hematology, Centre Léon Bérard, Lyon, France.
INSERM U590, Centre de Recherche de Cancérologie de Lyon, Centre Léon Bérard, Lyon, France.
出版信息
Clin Cancer Res. 2019 Nov 15;25(22):6606-6613. doi: 10.1158/1078-0432.CCR-18-3373. Epub 2019 Jul 10.
PURPOSE
Tyrosine kinase inhibitor (TKI) discontinuation is an emerging goal in chronic myelogenous leukemia (CML) management and several studies have demonstrated the feasibility of safely stopping imatinib. A sustained deep molecular response on long-term TKI is critical prior to attempting treatment-free remission. Reproducible results from several studies reported recently, failed to identify robust and reproducible predictive factors for the selection of the best candidates for successful TKI cessation.
PATIENTS AND METHODS
We conducted a prospective national phase II study evaluating the cessation of imatinib after at least 2 years of MR4.5 obtained on imatinib first-line in patients with chronic phase CML.
RESULTS
A total of 218 patients with chronic phase CML were involved in the study. The median follow-up after imatinib cessation was 23.5 (1-64) months, 2 patients died from unrelated causes, and 107 experienced a confirmed increase in levels defined as molecular recurrence. The molecular recurrence-free survival was 52% [95% confidence interval (CI), 45%-59%] at 6 months, and 50% (95% CI, 43%-57%) at 24 months. Droplet digital PCR (ddPCR) was used to evaluate more accurately low levels of in 175 of 218 patients at imatinib cessation. To apply positive ratios on the international scale (IS), a conversion factor was calculated for ddPCR and the significant cut-off point was established at 0.0023%. In a multivariate analysis, the duration of TKI (≥74.8 months) and ddPCR (≥0.0023%) were the two identified predictive factors of molecular recurrence, with = 0.0366 (HR, 0.635; 95% CI, 0.415-0.972] and = 0.008 (HR, 0.556; 95% CI, 0.360-0.858), respectively.
CONCLUSIONS
We conclude that the duration of TKI and residual leukemic cell load as determined by ddPCR are key factors for predicting successful treatment-free remission for patients with chronic phase CML..
目的
酪氨酸激酶抑制剂（TKI）停药是慢性髓性白血病（CML）管理的一个新兴目标，多项研究已经证明安全停用伊马替尼是可行的。在尝试无治疗缓解之前，长期 TKI 上的持续深度分子反应是至关重要的。最近几项研究报告的可重复结果未能确定用于选择成功 TKI 停药最佳候选者的强大且可重复的预测因素。
患者和方法
我们进行了一项前瞻性的全国性 II 期研究，评估了至少 2 年获得伊马替尼一线治疗慢性期 CML 患者的 MR4.5 后伊马替尼停药的情况。
结果
共有 218 例慢性期 CML 患者参与了该研究。伊马替尼停药后中位随访时间为 23.5（1-64）个月，2 例患者死于无关原因，107 例患者确诊水平升高定义为分子复发。分子无复发生存 6 个月时为 52%[95%置信区间（CI），45%-59%]，24 个月时为 50%（95%CI，43%-57%）。218 例患者中的 175 例在伊马替尼停药时使用液滴数字 PCR（ddPCR）更准确地评估 的低水平。为了在国际标准（IS）上应用阳性 比值，计算了 ddPCR 的转换因子，并确定了显著截断值为 0.0023%。在多变量分析中，TKI（≥74.8 个月）和 ddPCR（≥0.0023%）的持续时间是分子复发的两个确定的预测因素， = 0.0366（HR，0.635；95%CI，0.415-0.972]和 = 0.008（HR，0.556；95%CI，0.360-0.858）。
结论
我们的结论是，TKI 的持续时间和 ddPCR 确定的残留白血病细胞负荷是预测慢性期 CML 患者成功无治疗缓解的关键因素。
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