Dumas Pierre-Yves, Bertoli Sarah, Bérard Emilie, Largeaud Laetitia, Bidet Audrey, Delabesse Eric, Leguay Thibaut, Leroy Harmony, Gadaud Noémie, Rieu Jean Baptiste, Vial Jean-Philippe, Vergez François, Lechevalier Nicolas, Luquet Isabelle, Klein Emilie, Sarry Audrey, de Grande Anne-Charlotte, Pigneux Arnaud, Récher Christian
Service d'Hématologie Clinique et de Thérapie Cellulaire, CHU Bordeaux, F-33000 Bordeaux, France.
Université de Bordeaux, 33076 Bordeaux, France.
Cancers (Basel). 2020 Jul 24;12(8):2044. doi: 10.3390/cancers12082044.
Two recent phase 3 trials showed that outcomes for relapsed/refractory (R/R) -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/R -internal tandem duplication (ITD) acute myeloid leukemia (AML) patients in the Toulouse-Bordeaux DATAML registry. In the study, we included 316 patients with -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 ( = 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/R -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.
两项近期的3期试验表明，复发/难治性（R/R）-突变急性髓系白血病（AML）患者使用单一酪氨酸激酶抑制剂（TKI）（即quizartinib或gilteritinib）治疗后，预后可能得到改善。在本研究中，我们回顾性调查了图卢兹-波尔多DATAML登记处中R/R-内部串联重复（ITD）急性髓系白血病（AML）患者的特征和实际预后。在该研究中，我们纳入了316例接受强化化疗作为一线治疗的-ITD AML患者。完全缓解（CR）或无血液学恢复的完全缓解（CRi）率为75.2%，160例患者在一线无TKI治疗后复发/难治（n = 294）。在符合QUANTUM-R研究主要标准的R/R患者亚组中，48.9%接受了强化挽救方案；无人接受去甲基化药物或小剂量阿糖胞苷治疗。在接受无TKI强化治疗且CR1持续时间<6个月的R/R-ITD AML患者中，挽救化疗后的CR或CRi率为52.8%，这些结果使得39.6%的患者能够过渡到移植治疗。最后，在这个与QUANTUM-R标准治疗组匹配的队列中，总生存期（OS）中位数为7.0个月，1年、3年和5年OS率分别为30.2%、23.7%和21.4%。总之，这些实际数据表明二线治疗的强度可能会影响缓解率和移植率。此外，结果表明，在3期试验的对照组中纳入低强度方案（如小剂量阿糖胞苷或去甲基化药物）的患者可能会适得其反，并可能影响研究结果。
