Yang Yunfan, Liu Yuntao, Sun Hui, Meng Li, Lin Hai, Chen Chunyan, Hu Jianda, Shen Xuliang, Duan Minghui, Zhang Yanli, Abulaiti Dilinazi, Wang Jinghua, Zhu Hongqian, Hua Luoming, Leng Qing, Zhang Chun, Sun Lili, Li Weiming, Zhu Huanling, Liu Bingcheng, Wang Jianxiang
Department of Hematology, Institute of Hematology, West China Hospital of Sichuan University, Chengdu, Sichuan.
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020.
Haematologica. 2024 Dec 1;109(12):3965-3974. doi: 10.3324/haematol.2023.284892.
The aim of this study was to evaluate the efficacy and safety of flumatinib in later-line treatment of Chinese patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia ((CP-CML) previously treated with tyrosine kinase inhibitors (TKI). Patients with CML-CP were evaluated for probabilities of responses, including complete hematologic response (CHR), cytogenetic response, and molecular response (MR), and adverse events after the later-line flumatinib therapy. Of 336 enrolled patients with a median age 50 years, the median duration of treatment with flumatinib was 11.04 months (range, 2-25.23). Patients who achieved clinical responses at baseline showed maintenance of CHR, complete cytogenetic response (CCyR) or 2-log molecular response (MR2), major molecular response (MMR), and 4-log molecular response or deep molecular response (MR4/DMR) in 100%, 98.9%, 98.6%, and 92.9% of patients, respectively. CHR, CCyR/MR2, MMR, and MR4/DMR were achieved in 86.4%, 52.7%, 49.6%, and 23.5% of patients, respectively, who lacked the respective clinical responses at baseline. The patients without response at baseline, treated with flumatinib as a second-line TKI, having no resistance to prior TKI or only resistance to imatinib, with response to last TKI, and with BCR::ABL ≤10% had higher CCyR/MR2, MMR, or MR4/DMR rates. The adverse events observed during the later-line flumatinib treatment were tolerable and consistent with those reported with the first-line therapy. Flumatinib was effective and safe in patients who were resistant or intolerant to other TKI. In particular, second-line flumatinib treatment induced high response rates and was more beneficial to patients without previous second-generation TKI resistance, thus serving as a probable treatment option for these patients.
本研究旨在评估氟马替尼用于中国费城染色体阳性慢性期慢性髓性白血病（CP-CML）患者二线治疗的疗效和安全性，这些患者既往接受过酪氨酸激酶抑制剂（TKI）治疗。对CML-CP患者评估二线氟马替尼治疗后的反应概率，包括完全血液学缓解（CHR）、细胞遗传学缓解和分子学缓解（MR），以及不良事件。在336例入组患者中，年龄中位数为50岁，氟马替尼治疗的中位持续时间为11.04个月（范围2 - 25.23个月）。基线时达到临床反应的患者，CHR、完全细胞遗传学缓解（CCyR）或2-log分子学缓解（MR2）、主要分子学缓解（MMR）以及4-log分子学缓解或深度分子学缓解（MR4/DMR）的维持率分别为100%、98.9%、98.6%和92.9%。基线时未达到相应临床反应的患者，CHR、CCyR/MR2、MMR和MR4/DMR的实现率分别为86.4%、52.7%、49.6%和23.5%。基线时无反应的患者，作为二线TKI接受氟马替尼治疗，对既往TKI无耐药或仅对伊马替尼耐药，对末次TKI有反应，且BCR::ABL≤10%，其CCyR/MR2、MMR或MR4/DMR率更高。二线氟马替尼治疗期间观察到的不良事件可耐受，且与一线治疗报告的不良事件一致。氟马替尼对其他TKI耐药或不耐受的患者有效且安全。特别是，二线氟马替尼治疗诱导的缓解率较高，对既往无第二代TKI耐药的患者更有益，因此可作为这些患者的一种可能治疗选择。
