Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial
Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial
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DOI：
10.1016/s1470-2045(10)70233-3
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发表时间：
2010-11-01
期刊：
影响因子：
51.1
通讯作者：
Rousselot, Philippe
中科院分区：
文献类型：
--
作者：
Mahon, Francois-Xavier;Rea, Delphine;Rousselot, Philippe
背景伊马替尼治疗可显著提高慢性髓性白血病（CML）患者的生存率，但对于长期停药是否安全尚不清楚。我们的目的是评估伊马替尼完全分子缓解（CMR）患者在服用伊马替尼期间是否可以停药而不会发生分子复发。方法在我们的前瞻性、多中心、非随机停止伊马替尼（STIM）研究中，18岁及以上CML患者和CMR患者（BCR-ABL和ABL水平下降5-log，定量RT-PCR检测不到转录物）停止伊马替尼治疗（持续时间为> - 2年）。接受过免疫调节治疗（除了干扰素）、其他恶性肿瘤治疗或同种异体造血干细胞移植的患者不包括在内。患者在法国的19个参与机构登记。在这个中期分析中，使用RT-PCR对随访至少12个月的患者进行复发率评估。在分子复发的患者中重新引入伊马替尼。本研究已在ClinicalTrials.gov注册，编号NCT00478985。结果在2007年7月9日至2009年12月17日期间入组了100例患者。中位随访为17个月（范围1-30），69例患者至少随访12个月（中位24个月，范围13-30）。69例患者中有42例（61%）复发（6个月前40例，7个月1例，19个月1例）。在12个月时，这69名患者持续CMR的概率为41% （95% CI 29-52）。所有复发患者对伊马替尼的再次使用都有反应：42例复发患者中有16例BCR-ABL水平下降，26例在伊马替尼再次使用后达到持续的CMR。对于持续CMR至少2年的患者，伊马替尼可以安全停药。在这种情况下，伊马替尼停药对分子无复发生存产生了有希望的结果，这增加了至少在一些患者中，酪氨酸激酶抑制剂可能治愈CML的可能性。
Background Imatinib treatment significantly improves survival in patients with chronic myeloid leukaemia (CML), but little is known about whether treatment can safely be discontinued in the long term. We aimed to assess whether imatinib can be discontinued without occurrence of molecular relapse in patients in complete molecular remission (CMR) while on imatinib.Methods In our prospective, multicentre, non-randomised Stop Imatinib (STIM) study, imatinib treatment (of >2 years duration) was discontinued in patients with CML who were aged 18 years and older and in CMR (>5-log reduction in BCR-ABL and ABL levels and undetectable transcripts on quantitative RT-PCR). Patients who had undergone immunomodulatory treatment (apart from interferon alpha), treatment for other malignancies, or allogeneic haemopoietic stem-cell transplantation were not included. Patients were enrolled at 19 participating institutions in France. In this interim analysis, rate of relapse was assessed by use of RT-PCR for patients with at least 12 months of follow-up. Imatinib was reintroduced in patients who had molecular relapse. This study is registered with ClinicalTrials.gov, number NCT00478985.Findings 100 patients were enrolled between July 9, 2007, and Dec 17, 2009. Median follow-up was 17 months (range 1-30), and 69 patients had at least 12 months follow-up (median 24 months, range 13-30). 42 (61%) of these 69 patients relapsed (40 before 6 months, one patient at month 7, and one at month 19). At 12 months, the probability of persistent CMR for these 69 patients was 41% (95% CI 29-52). All patients who relapsed responded to reintroduction of imatinib: 16 of the 42 patients who relapsed showed decreases in their BCR-ABL levels, and 26 achieved CMR that was sustained after imatinib rechallenge.Interpretation Imatinib can be safely discontinued in patients with a CMR of at least 2 years duration. Imatinib discontinuation in this setting yields promising results for molecular relapse-free survival, raising the possibility that, at least in some patients, CML might be cured with tyrosine kinase inhibitors.