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Ponatinib 对比早期一代酪氨酸激酶抑制剂用于新诊断费城阳性急性淋巴细胞白血病一线治疗的疗效。

Efficacy of Ponatinib Versus Earlier Generation Tyrosine Kinase Inhibitors for Front-line Treatment of Newly Diagnosed Philadelphia-positive Acute Lymphoblastic Leukemia.

机构信息

University of Texas MD Anderson Cancer Center, Houston, TX.

Analysis Group, Inc., Boston, MA.

出版信息

Clin Lymphoma Myeloma Leuk. 2018 Apr;18(4):257-265. doi: 10.1016/j.clml.2018.02.010. Epub 2018 Feb 17.

Abstract

INTRODUCTION

Complete molecular response (CMR) and 2- and 3-year overall survival (OS) were compared for patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph ALL) who had undergone front-line combination chemotherapy plus ponatinib versus combination therapy plus earlier generation tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, and nilotinib).

PATIENTS AND METHODS

We identified 26 Ph ALL studies: 25 of earlier generation TKIs and 1 of ponatinib. The outcomes from studies of combination chemotherapy plus earlier generation TKIs were summarized using pooled estimates with 95% confidence intervals (CIs) from a random-effects meta-analysis. A binomial distribution was assumed to calculate the 95% CIs for the results from the single-arm combination chemotherapy plus ponatinib trial. Adjusted logistic meta-regression analyses were used to compare the outcomes between the TKI groups.

RESULTS

The percentage of patients achieving a CMR was greater with combination chemotherapy plus ponatinib (79%) than the pooled percentage of patients achieving a CMR with combination chemotherapy plus earlier generation TKIs (34%). Greater OS was observed with ponatinib compared with the pooled OS for earlier generation TKIs (2-year, 83% vs. 58%; 3-year, 79% vs. 50%). Odds ratios for ponatinib versus earlier generation TKIs were 6.09 (95% CI, 1.16-31.90; P = .034) for CMR, 3.70 (95% CI, 0.93-14.73; P = .062) for 2-year OS, and 4.49 (95% CI, 1.00-20.13; P = .050) for 3-year OS.

CONCLUSION

Ponatinib plus chemotherapy might be associated with better outcomes than chemotherapy with earlier generation TKIs in patients with newly diagnosed Ph ALL.

摘要

简介

我们比较了初诊费城染色体阳性急性淋巴细胞白血病(Ph ALL)患者一线联合化疗加 ponatinib 与联合治疗加早期一代酪氨酸激酶抑制剂(TKI;伊马替尼、达沙替尼和尼洛替尼)的完全分子反应(CMR)和 2 年、3 年总生存(OS)。

方法

我们确定了 26 项 Ph ALL 研究:25 项为早期一代 TKI,1 项为 ponatinib。使用随机效应荟萃分析的汇总估计和 95%置信区间(CI)汇总了早期一代 TKI 联合化疗研究的结果。采用二项分布假设计算单臂联合化疗加 ponatinib 试验的结果 95%CI。调整后的逻辑回归荟萃分析用于比较 TKI 组之间的结果。

结果

与联合化疗加早期一代 TKI 的 CMR 百分比(34%)相比,联合化疗加 ponatinib 的 CMR 百分比更高(79%)。与早期一代 TKI 的汇总 OS 相比,ponatinib 的 OS 更高(2 年,83%比 58%;3 年,79%比 50%)。ponatinib 与早期一代 TKI 的比值比为 CMR(95%CI,1.16-31.90;P=.034)6.09,2 年 OS(95%CI,0.93-14.73;P=.062)3.70,3 年 OS(95%CI,1.00-20.13;P=.050)4.49。

结论

在初诊 Ph ALL 患者中,ponatinib 联合化疗可能比化疗联合早期一代 TKI 具有更好的疗效。

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