Legros Laurence, Nicolini Franck E, Etienne Gabriel, Rousselot Philippe, Rea Delphine, Giraudier Stéphane, Guerci-Bresler Agnès, Huguet Françoise, Gardembas Martine, Escoffre Martine, Ianotto Jean-Christophe, Noël Marie-Pierre, Varet Bruno R, Pagliardini Thomas, Touitou Irit, Morisset Stéphane, Mahon Francois-Xavier
Hematology Department, Nice University Hospital, Nice, France.
Valrose Institute of Biology, National Center for Scientific Research (CNRS) Unit 7277, National Institute of Health and Medical Research (INSERM) Unit 1091, Nice, France.
Cancer. 2017 Nov 15;123(22):4403-4410. doi: 10.1002/cncr.30885. Epub 2017 Jul 25.
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.
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.
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.
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. Cancer 2017;123:4403-10. © 2017 American Cancer Society.
多项研究表明，接受酪氨酸激酶抑制剂（TKI）治疗并实现且维持深度分子反应（DMR）的慢性髓性白血病（CML）患者中，约有一半能够成功停药。对于出现分子复发的患者，重新开始治疗后可迅速恢复DMR。
作者报告了RE-STIM研究的结果，这是一项法国的观察性多中心研究，评估了70例在首次停药尝试失败后再次尝试停用TKI的患者的无治疗缓解（TFR）情况。在第二次TKI停药尝试后，所有患者重新开始治疗的触发因素是主要分子反应的丧失。
中位随访时间为38.3个月（范围4.7 - 117个月），45例患者（64.3%）在中位停药时间5.3个月（范围2 - 42个月）后丧失了主要分子反应。12个月、24个月和36个月时的TFR率分别为48%（95%置信区间[CI]，37.6% - 61.5%）、42%（95% CI，31.5% - 55.4%）和35%（95% CI，24.4% - 49.4%）。未发生进展至晚期CML的情况，重新引入TKI后未观察到疗效问题。在单因素分析中，首次TKI停药尝试后分子复发的速度是唯一与结局显著相关的因素。在首次TKI停药后的前3个月内仍处于DMR的患者中，24个月时的TFR率为72%（95% CI, 48.8% - 100%），其他患者为36%（95% CI, 25.8% - 51.3%）。
本研究首次证明第二次TKI停药尝试是安全的，且首次TKI停药尝试失败并不排除第二次成功尝试。《癌症》2017年；123:4403 - 10。© 2017美国癌症协会。
