University of Texas MD Anderson Cancer Center, Houston, TX.
Analysis Group, Inc., Boston, MA.
Clin Lymphoma Myeloma Leuk. 2018 Apr;18(4):257-265. doi: 10.1016/j.clml.2018.02.010. Epub 2018 Feb 17.
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).
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.
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.
Ponatinib plus chemotherapy might be associated with better outcomes than chemotherapy with earlier generation TKIs in patients with newly diagnosed Ph ALL.
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)。
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。
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。
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。