Switching to nilotinib in patients with chronic myeloid leukemia in chronic phase with molecular suboptimal response to frontline imatinib: SENSOR final results and BIM polymorphism substudy
Switching to nilotinib in patients with chronic myeloid leukemia in chronic phase with molecular suboptimal response to frontline imatinib: SENSOR final results and BIM polymorphism substudy
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DOI：
10.1016/j.leukres.2016.09.009
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发表时间：
2016-12-01
影响因子：
2.7
通讯作者：
Taniwaki, Masafumi
中科院分区：
文献类型：
--
作者：
Miyamura, Koichi;Miyamoto, Toshihiro;Taniwaki, Masafumi
对一线伊马替尼分子应答（MR）欠佳的慢性期慢性髓细胞白血病患者的最佳管理尚未确定。我们报告了SENSOR的最终结果，该结果评估了尼洛替尼在这种情况下的疗效/安全性。一项子研究评估了BIM多态性是否影响尼洛替尼的应答。在这项单组、多中心研究中，根据欧洲白血病网2009标准（完全细胞遗传学缓解，但不是主要MR [MMR]），在一线伊马替尼治疗≥ 18个月后出现次优MR的日本患者接受尼洛替尼400 mg每日两次治疗，持续24个月。在中心实验室评价MR、BCR-ABL 1突变/变体和BIM多态性。主要终点为12个月时的MMR率（无效假设为40%）。在45例患者中（中位暴露时间为22.08个月），39例完成研究，6例中止研究。在12个月和24个月时，分别有51.1%（95% CI，35.8%-66.3%）和66.7%（95% CI，51.0%-80.0%）的患者达到MMR。24个月时的累积MMR发生率为75.6%。在分析的40例患者中，12例患者中有10例（83.3%）和28例患者中有17例（60.7%）在24个月时达到MMR。安全性特征可通过减量和中断治疗进行管理。尼洛替尼为伊马替尼疗效欠佳的患者提供了临床获益，BIM多态性不影响MMR的实现。(C)2016爱思唯尔有限公司版权所有
Optimal management of patients with chronic myeloid leukemia in chronic phase with suboptimal molecular response (MR) to frontline imatinib is undefined. We report final results from SENSOR, which evaluated efficacy/safety of nilotinib in this setting. A substudy assessed whether BIM polymorphisms impacted response to nilotinib. In this single-arm, multicenter study, Japanese patients with suboptimal MR per European LeukemiaNet 2009 criteria (complete cytogenetic response, but not major MR [MMR]) after >= 18 months of frontline imatinib received nilotinib 400 mg twice daily for 24 months. MR, BCR-ABL1 mutations/variants, and BIM polymorphisms were evaluated in a central laboratory. Primary endpoint was the MMR rate at 12 months (null hypothesis of 40%). Of 45 patients (median exposure, 22.08 months), 39 completed the study and six discontinued. At 12 and 24 months, 51.1% (95% CI, 35.8%-66.3%) and 66.7% (95% CI, 51.0%-80.0%) achieved MMR, respectively. Cumulative MMR incidence by 24 months was 75.6%. Of 40 patients analyzed, 10 of 12 (83.3%) with and 17 of 28 (60.7%) without BIM polymorphisms achieved MMR at 24 months. The safety profile was manageable with dose reductions and interruptions. Nilotinib provided clinical benefit for patients with suboptimal response to imatinib, and BIM polymorphisms did not influence MMR achievement. (C) 2016 Elsevier Ltd. All rights reserved.