Real-World Outcomes of Patients with Refractory or RelapsedFLT3-ITD Acute Myeloid Leukemia: A Toulouse-Bordeaux DATAML Registry Study
Real-World Outcomes of Patients with Refractory or RelapsedFLT3-ITD Acute Myeloid Leukemia: A Toulouse-Bordeaux DATAML Registry Study
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DOI：
10.3390/cancers12082044
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发表时间：
2020-08-01
期刊：
影响因子：
5.2
通讯作者：
Recher, Christian
中科院分区：
文献类型：
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作者：
Dumas, Pierre-Yves;Bertoli, Sarah;Recher, Christian
最近的两项 3 期试验表明，单药酪氨酸激酶抑制剂 (TKI)（即 quizartinib 或 gilteritinib）可能会改善复发/难治性 (R/R)FLT3 突变的急性髓系白血病 (AML) 患者的预后。在当前的研究中，我们回顾性研究了图卢兹-波尔多 DATAML 登记处 R/RFLT3 内部串联重复 (ITD) 急性髓系白血病 (AML) 患者的特征和现实世界结果。在这项研究中，我们纳入了 316 名 FLT3-ITD AML 患者，他们接受强化化疗作为一线治疗。完全缓解（CR）或无血液学恢复的 CR（CRi）率为 75.2%，160 名患者在一线无 TKI 治疗后出现 R/R（n = 294）。在满足 QUANTUM-R 研究主要标准的 R/R 患者亚组中，48.9% 的患者接受了强化挽救方案；没有人接受低甲基化药物或低剂量阿糖胞苷。在接受强化无TKI治疗的CR1持续时间<6个月的R/RFLT3-ITD AML患者中，挽救性化疗后的CR或CRi率为52.8%，并且该结果允许39.6%的病例进行桥移植。最后，在这个 QUANTUM-R 标准臂匹配队列中，中位总生存期 (OS) 为 7.0 个月，1 年、3 年和 5 年 OS 分别为 30.2%、23.7% 和 21.4%。总之，这些现实世界的数据表明二线治疗的强度可能会影响反应和移植率。此外，结果表明，将接受低强度治疗方案（例如低剂量阿糖胞苷或低甲基化药物）的患者纳入 3 期试验的对照组可能会适得其反，并可能损害研究结果。
Two recent phase 3 trials showed that outcomes for relapsed/refractory (R/R)FLT3-mutated acute myeloid leukemia (AML) patients may be improved by a single-agent tyrosine kinase inhibitor (TKI) (i.e., quizartinib or gilteritinib). In the current study, we retrospectively investigated the characteristics and real-world outcomes of R/RFLT3-internal tandem duplication (ITD) acute myeloid leukemia (AML) patients in the Toulouse-Bordeaux DATAML registry. In the study, we included 316 patients withFLT3-ITD AML that received intensive chemotherapy as a first-line treatment. The rate of complete remission (CR) or CR without hematological recovery (CRi) was 75.2%, and 160 patients were R/R after a first-line TKI-free treatment (n= 294). Within the subgroup of R/R patients that fulfilled the main criteria of the QUANTUM-R study, 48.9% received an intensive salvage regimen; none received hypomethylating agents or low-dose cytarabine. Among the R/RFLT3-ITD AML patients with CR1 durations < 6 months who received intensive TKI-free treatment, the rate of CR or CRi after salvage chemotherapy was 52.8%, and these results allowed a bridge to be transplanted in 39.6% of cases. Finally, in this QUANTUM-R standard arm-matched cohort, the median overall survival (OS) was 7.0 months and 1-, 3- and 5-year OS were 30.2%, 23.7% and 21.4%, respectively. To conclude, these real-world data show that the intensity of the second-line treatment likely affects response and transplantation rates. Furthermore, the results indicate that including patients with low-intensity regimens, such as low-dose cytarabine or hypomethylating agents, in the control arm of a phase 3 trial may be counterproductive and could compromise the results of the study.