氟马替尼治疗伊马替尼耐药或不耐受慢性粒细胞白血病的效果及安全性  

Efficacy and safety of flumatinib in treatment of imatinib-resistant or imatinib-intolerant patients with chronic myeloid leukemia

作　　者：郭勇鑫 陆天 陈文明[2] 郭文文 杨水个 梁艳艳[1] 孙忠亮[1] 孙道萍[1] Guo Yongxin;Lu Tian;Chen Wenming;Guo Wenwen;Yang Shuige;Liang Yanyan;Sun Zhongliang;Sun Daoping(Department of Hematology,Jining No.I People's Hospital Affiliated to Shandong First Medical University,Jining 272011,China;Department of Oncology,Jining No.1 People's Hospital Affiliated to Shandong First Medical University,Jining 272011,China)

机构地区：[1]山东第一医科大学附属济宁市第一人民医院血液内科,济宁272011 [2]山东第一医科大学附属济宁市第一人民医院肿瘤科,济宁272011

出　　处：《白血病．淋巴瘤》2023年第1期45-50,共6页Journal of Leukemia & Lymphoma

基　　金：山东省自然科学基金(ZR2020MH207、ZR2020MH251)。

摘　　要：目的探讨氟马替尼治疗伊马替尼耐药或不耐受的慢性粒细胞白血病慢性期(CML-CP)患者的效果及安全性。方法回顾性分析2020年4月至2021年5月就诊于济宁市第一人民医院9例对一线伊马替尼耐药或不耐受而接受氟马替尼治疗的CML-CP患者的临床资料。评估患者血液学、细胞遗传学和分子学反应及无进展生存(PFS)、无事件生存(EFS)和不良反应发生情况。结果9例CML-CP患者中,包括4例伊马替尼耐药及5例伊马替尼不耐受患者。氟马替尼中位治疗时间为17个月(1~25个月)。除1例患者因4级血小板减少等不良反应早期停用氟马替尼外,其余8例患者中7例在氟马替尼治疗3、6、12个月时获得最佳治疗反应。至2022年4月随访结束时,获得完全细胞遗传学反应(CCyR)、主要分子学反应(MMR)和分子学反应4.5(MR4.5)分别有7、7、6例患者,获得CCyR、MMR和MR4.5的中位时间分别为4.5个月(3~6个月)、12个月(3~12个月)和15个月(3~21个月)。中位随访17个月(11~25个月),9例患者中7例EFS,8例持续应用氟马替尼的患者均PFS。9例患者应用氟马替尼治疗后6例出现血液学不良反应,其中2例为3~4级;非血液学不良反应主要包括腹泻(4例)、肌肉酸痛(2例)、乏力(2例)及肝功能损害(2例),均为1~2级。结论氟马替尼治疗伊马替尼耐药或不耐受的CML-CP患者疗效显著,且耐受性良好。Objective To investigate the fficacy and safety of flumatinib in the treatment of imatinib-resistant or imatinib-intolerant patients with chronic phase chronic myelogenous leukemia(CML-CP).Methods The clinical data of 9 CML-CP patients who received flumatinib after imatinib resistance or intolerance in Jining No.1 People's Hospital from April 2020 to May 2021 were retrospectively analyzed.Patients were evaluated for the hematologic,cytogenetic and molecular responses,progression-free survival(PFS),event-free survival(EFS),and adverse reactions.Results Among 9 CML-CP patients,there were 4 imatinib-resistant patients and 5 imatinib-intolerant patients.The median duration of flumatinib exposure was 17 months(1-25 months).Except for 1 case who discontinued flumatinib early due to grade 4 thrombocytopenia and other adverse reactions,7 of the remaining 8 cases achieved the best response at 3,6 and 12 months of flumatinib therapy.By the end of follow-up in April 2022,7,7 and 6 patients achieved complete cytogenetic response(CCyR),major molecular response(MMR)and molecular response 4.5(MR4.5),respectively.The median time to achieving CCyR,MMR and MR4.5 was 4.5 months(3-6 months),12 months(3-12 months)and 15 months(3-21 months),respectively.Within 17 months(11-25 months)of follow-up,7 of the 9 patients had EFS and 8 patients with continuous flumatinib had PFS.Among 9 patients treated with flumatinib,hematologic adverse reactions were observed in 6 cases,and grade 3-4 hematologic adverse reactions occurred in 2 cases.Non-hematologic reactions events mainly included diarrhea(4 cases),muscle ache(2 cases),fatigue(2 cases)and liver damage(2 cases),which were all grade 1-2.Conclusions Flumatinib is effective and well tolerated in the treatment of imatinib-resistant or imatinib-intolerant CML-CP patients.

关 键 词：白血病 髓系 慢性 BCR-ABL阳性 氟马替尼 伊马替尼 抗药性 治疗结果 

分 类 号：R733.7[医药卫生—肿瘤]