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Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results.尼洛替尼治疗伊马替尼耐药或不耐受的慢性期慢性髓性白血病患者有效:24 个月随访结果。
Blood. 2011 Jan 27;117(4):1141-5. doi: 10.1182/blood-2010-03-277152. Epub 2010 Nov 22.
2
Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia.达沙替尼与伊马替尼治疗新诊断的慢性期慢性髓性白血病。
N Engl J Med. 2010 Jun 17;362(24):2260-70. doi: 10.1056/NEJMoa1002315. Epub 2010 Jun 5.
3
Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib.达沙替尼 100mg 每日治疗可强效、短暂地抑制 BCR-ABL,对于对伊马替尼耐药、治疗反应欠佳或不耐受的慢性期慢性髓性白血病患者,可迅速并持久地获得细胞遗传学反应,且无进展生存率较高。
Haematologica. 2010 Feb;95(2):232-40. doi: 10.3324/haematol.2009.011452.
4
Nilotinib as front-line treatment for patients with chronic myeloid leukemia in early chronic phase.尼罗替尼作为早期慢性期慢性髓性白血病患者的一线治疗药物。
J Clin Oncol. 2010 Jan 20;28(3):392-7. doi: 10.1200/JCO.2009.25.4896. Epub 2009 Dec 14.
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Results of dasatinib therapy in patients with early chronic-phase chronic myeloid leukemia.达沙替尼治疗慢性髓性白血病早期慢性期患者的疗效。
J Clin Oncol. 2010 Jan 20;28(3):398-404. doi: 10.1200/JCO.2009.25.4920. Epub 2009 Dec 14.
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Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet.慢性髓性白血病:欧洲白血病网络概念与管理建议的更新
J Clin Oncol. 2009 Dec 10;27(35):6041-51. doi: 10.1200/JCO.2009.25.0779. Epub 2009 Nov 2.
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Nilotinib for the frontline treatment of Ph(+) chronic myeloid leukemia.尼洛替尼用于 Ph(+) 慢性髓性白血病的一线治疗。
Blood. 2009 Dec 3;114(24):4933-8. doi: 10.1182/blood-2009-07-232595. Epub 2009 Oct 12.
8
The use of nilotinib or dasatinib after failure to 2 prior tyrosine kinase inhibitors: long-term follow-up.在两种先前的酪氨酸激酶抑制剂治疗失败后使用尼罗替尼或达沙替尼:长期随访
Blood. 2009 Nov 12;114(20):4361-8. doi: 10.1182/blood-2009-05-221531. Epub 2009 Sep 3.
9
Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of high-risk, Philadelphia-positive chronic myeloid leukemia: a European LeukemiaNet Study.伊马替尼每日400毫克与800毫克用于高危、费城染色体阳性慢性髓性白血病一线治疗的比较:一项欧洲白血病网研究
Blood. 2009 May 7;113(19):4497-504. doi: 10.1182/blood-2008-12-191254. Epub 2009 Mar 4.
10
Survival benefit with imatinib mesylate versus interferon-alpha-based regimens in newly diagnosed chronic-phase chronic myelogenous leukemia.甲磺酸伊马替尼与基于α-干扰素方案治疗新诊断慢性期慢性粒细胞白血病的生存获益比较
Blood. 2006 Sep 15;108(6):1835-40. doi: 10.1182/blood-2006-02-004325. Epub 2006 May 18.

一线治疗失败后慢性期慢性髓性白血病患者达到不同水平细胞遗传学反应的临床意义:完全细胞遗传学反应是否是唯一理想的终点?

The clinical significance of achieving different levels of cytogenetic response in patients with chronic phase chronic myeloid leukemia after failure to front-line therapy: is complete cytogenetic response the only desirable endpoint?

机构信息

Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, USA.

出版信息

Clin Lymphoma Myeloma Leuk. 2011 Oct;11(5):421-6. doi: 10.1016/j.clml.2011.06.009. Epub 2011 Aug 10.

DOI:10.1016/j.clml.2011.06.009
PMID:21831744
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3215673/
Abstract

UNLABELLED

Many patients with chronic myeloid leukemia who have failed initial therapy with a tyrosine kinase inhibitor achieve a cytogenetic response that is not complete (ie, partial or minor). This study analyzes the clinical benefit of such responses and identifies value in achieving such responses. Patients with less than complete cytogenetic response to second -line therapy or beyond should be considered to have benefit from therapy and the value of this considered in the context of which alternative options are available.

BACKGROUND

Complete cytogenetic response (CCyR) is the gold standard for response to therapy for patients with chronic myeloid leukemia (CML) because it is associated with a survival benefit. However, patients who have failed initial therapy with a tyrosine kinase inhibitor (TKI) frequently achieve only partial or minor cytogenetic responses. The clinical benefit of such responses is unclear.

PATIENTS AND METHODS

We analyzed the records of all 165 consecutive patients treated in clinical trials with TKI as second-line therapy or beyond after failure to prior imatinib therapy.

RESULTS

A CCyR was achieved with second-line TKI therapy or beyond in 52% of patients, whereas 7% achieved a partial cytogenetic response (PCyR), 14% a minor cytogenetic response (mCyR), 14% complete hematologic response (CHR) only, and 17% no response. The 3-year survival probability was 98% for those with CCyR, compared to 83% with PCyR, 83% for mCyR, 76% for CHR, and 71% for no response. Survival free from transformation rates at 3 years were 93%, 73%, 84%, 88%, and 0%, respectively.

CONCLUSIONS

CCyR is associated with the greatest survival benefit among patients treated with second-line therapy or beyond and remains the optimal cytogenetic goal of therapy. However, patients with partial and minor cytogenetic response derive a benefit compared to patients who have no response. This benefit should be recognized and evaluated against any alternative option available to a given patient before a change in therapy is recommended.

摘要

未加标签

许多慢性髓性白血病患者在初始酪氨酸激酶抑制剂治疗失败后会出现不完全的细胞遗传学反应(即部分或轻微)。本研究分析了这种反应的临床获益,并确定了实现这种反应的价值。对于二线治疗或以上治疗反应不完全的患者,应考虑从治疗中获益,并在考虑可用替代方案的情况下评估这种获益的价值。

背景

完全细胞遗传学反应(CCyR)是慢性髓性白血病(CML)患者治疗反应的金标准,因为它与生存获益相关。然而,在初始酪氨酸激酶抑制剂(TKI)治疗失败的患者中,经常只能达到部分或轻微的细胞遗传学反应。这种反应的临床获益尚不清楚。

患者和方法

我们分析了在先前伊马替尼治疗失败后接受 TKI 二线或以上治疗的 165 例连续患者临床试验记录。

结果

52%的患者在二线 TKI 治疗或以上治疗中达到 CCyR,而 7%的患者达到部分细胞遗传学反应(PCyR),14%的患者达到轻微细胞遗传学反应(mCyR),14%的患者达到完全血液学反应(CHR),17%的患者无反应。CCyR 患者的 3 年生存率为 98%,而 PCyR 患者为 83%,mCyR 患者为 83%,CHR 患者为 76%,无反应患者为 71%。3 年无转化生存率分别为 93%、73%、84%、88%和 0%。

结论

CCyR 与二线或以上治疗患者的最大生存获益相关,仍然是治疗的最佳细胞遗传学目标。然而,与无反应患者相比,部分和轻微细胞遗传学反应的患者从中获益。在建议改变治疗之前,应认识到这种获益,并根据患者的具体情况评估任何可用的替代方案。