University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Box 428, Houston, TX 77030, USA.
J Clin Oncol. 2011 Nov 10;29(32):4260-5. doi: 10.1200/JCO.2011.36.0693. Epub 2011 Oct 11.
The response definitions proposed by the European LeukemiaNet (ELN) are defined on the basis of imatinib front-line therapy. It is unknown whether these definitions apply to patients treated with second-generation tyrosine kinase inhibitors (TKIs).
One hundred sixty-seven patients with newly diagnosed chronic myelogenous leukemia (CML) in chronic phase were treated with second-generation TKIs in phase II trials (nilotinib, 81; dasatinib, 86). Median follow-up was 33 months. Event-free survival (EFS) was measured from the start of treatment to the date of loss of complete hematologic response, loss of complete or major cytogenetic response, discontinuation of therapy for toxicity or lack of efficacy, progression to accelerated or blastic phases, or death at any time.
Overall, 155 patients (93%) achieved complete cytogenetic response (CCyR), including 146 (87%) with major molecular response (MMR; complete in 46 patients [28%]). According to the ELN definitions, the rates of suboptimal response were 0%, 2%, 1%, and 12% at 3, 6, 12, and 18 months of therapy, respectively. There was no difference in EFS and CCyR duration between patients who achieved CCyR with and without MMR across all the landmark times of 3, 6, 12, and 18 months.
The use of second-generation TKIs as initial therapy in CML induces high rates of CCyR at early time points. The ELN definitions of response proposed for imatinib therapy are not applicable in this setting. We propose that achievement of CCyR and partial cytogenetic response at 3 months should be considered optimal and suboptimal responses, respectively. The achievement of MMR offered no advantage over CCyR in defining long-term outcome in patients with newly diagnosed CML treated with second-generation TKIs.
欧洲白血病网络（ELN）提出的反应定义是基于一线伊马替尼治疗的基础上定义的。这些定义是否适用于接受第二代酪氨酸激酶抑制剂（TKI）治疗的患者尚不清楚。
167 例新诊断的慢性髓性白血病（CML）慢性期患者在 II 期临床试验中接受第二代 TKI 治疗（尼洛替尼 81 例，达沙替尼 86 例）。中位随访时间为 33 个月。无事件生存（EFS）从治疗开始到完全血液学反应丧失、完全或主要细胞遗传学反应丧失、因毒性或疗效不佳停止治疗、加速或原始细胞危象进展或任何时间死亡的日期进行测量。
总体而言，155 例患者（93%）达到完全细胞遗传学反应（CCyR），其中 146 例（87%）达到主要分子反应（MMR；46 例完全缓解[28%]）。根据 ELN 的定义，在治疗后 3、6、12 和 18 个月时，亚最佳反应率分别为 0%、2%、1%和 12%。在所有 3、6、12 和 18 个月的里程碑时间点上，达到 CCyR 且无 MMR 的患者之间的 EFS 和 CCyR 持续时间没有差异。
第二代 TKI 作为 CML 的初始治疗，在早期即可达到高 CCyR 率。针对伊马替尼治疗提出的反应定义不适用于这种情况。我们建议，在接受第二代 TKI 治疗的新诊断 CML 患者中，3 个月时达到 CCyR 和部分细胞遗传学反应应分别被视为最佳和次佳反应。在接受第二代 TKI 治疗的新诊断 CML 患者中，达到 MMR 并没有比达到 CCyR 更能定义长期预后。
