慢性髓系白血病慢性期TKI治疗未达最佳反应或不耐受患者转换氟马替尼的有效性和安全性临床观察  

Efficacy and safety of switching to flumatinib in patients with chronic myeloid leukemia who have not achieved optimal response or are intolerant to TKI treatment

作　　者：杨松凡 文钦 张颖[3] 吕敬龙 舒华娥 颜红菊 张诚 魏锦[1] 张曦 YANG Songfan;WEN Qin;ZHANG Ying;LYU Jinglong;SHU Hua’e;YAN Hongju;ZHANG Cheng;WEI Jin;ZHANG Xi(Department of Hematology,Affiliated Hospital of North Sichuan Medical College,Nanchong,Sichuan Province,637002;State Key Laboratory of Trauma and Chemical Poisoning,Medical Center of Hematology,Military Key Clinical Specialty,Chongqing Key Clinical Specialty,Chongqing Key Laboratory of Hematology and Microenvironment,Second Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing,400037;Department of Hematology,the Second Affiliated Hospital of Chongqing Medical University,Chongqing,401336;Department of Hematology,Three Gorges Hospital Affiliated to Chongqing Medical University,Chongqing,404100;Department of Hematology,Kaizhou People’s Hospital,Chongqing,405400;Jinfeng Laboratory,Chongqing,401329,China)

机构地区：[1]川北医学院附属医院血液科,南充637002 [2]陆军军医大学(第三军医大学)第二附属医院血液病医学中心,全军临床重点专科,创伤与化学中毒全国重点实验室,重庆市临床重点专科,血液病与微环境重庆市重点实验室,重庆400037 [3]重庆医科大学第二附属医院血液科,重庆401336 [4]重庆大学附属三峡医院血液科,重庆404100 [5]开州区人民医院血液科,重庆405400 [6]金凤实验室,重庆401329

出　　处：《陆军军医大学学报》2024年第4期340-346,共7页Journal of Army Medical University

基　　金：重庆市科卫联合医学科研面上项目(2023MSXM079);重庆市技术创新与应用发展专项面上项目(cstc2019jscx-msxmX0147)。

摘　　要：目的 观察TKI未达最佳反应或不耐受的慢性髓系白血病-慢性期(chronic myelogenous leukemia-chronicphase, CML-CP)患者转换氟马替尼治疗的效果及安全性。方法 从重庆市医院及川北医学院附属医院共5家医院收集2020年2月至2022年8月对一线伊马替尼、达沙替尼、尼洛替尼未达最佳反应或不耐受,转换氟马替尼(600 mg/d)治疗的患者,观察氟马替尼的疗效及安全。统计患者治疗3、6、12个月时最佳反应率及主要分子学反应(major molecular response, MMR)率、累积完全细胞遗传学反应(complete cytogenetic response, CCyR)率、累积MMR率、累积深度分子学反应(deep molecular response, DMR)率、无进展生存(progression-free survival, PFS)、无事件生存(event-free survival, EFS)情况及不良反应情况。结果 共纳入100例CML-CP患者,中位随访时间为18(3~36)个月,3、6、12个月最佳反应率分别为92.6%(88/95)、94.4%(85/90)和92.9%(79/85),随访截止至2023年8月20日,累积CCyR、MMR率分别为98.0%(98/100)、81.9%(77/94),达CCyR和MMR的中位时间均为3个月,累积DMR率为51.0%(51/100)。随访时间内,PFS率为100.0%(100/100),1年EFS率为85.6%(75/90)。氟马替尼最常见非血液学不良反应为腹泻腹痛(7.0%),其次为肾功能损害(6.0%)、肌肉骨骼疼痛(2.0%);血液学不良反应主要有血小板减少(12.0%)、贫血(6.0%)和白细胞减少(2.0%)。结论 氟马替尼治疗TKI未达最佳反应或不耐受的CML-CP患者有较好的MMR和DMR,耐受性及安全性良好。Objective To observe the efficacy and safety of flumatinib conversion in chronic myelogenous leukemia-chronicphase(CML-CP)patients with suboptimal TKI response or intolerance.Methods Patients who did not have the best response or intolerance to first-line imatinib,dasatinib,and nilotinib and switched to flumatinib(600 mg/d)from February 2020 to August 2022 were collected from 5 hospitals from Chongqing and affiliated hospitals of North Sichuan Medical College.The efficacy and safety of flumatinib were observed.The optimal response rate,major molecular response(MMR),cumulative complete cytogenetic response(CCyR)rate,cumulative MMR rate,cumulative deep molecular response(DMR),progression-free survival(PFS),event-free survival(EFS)and adverse reactions in 3,6 and 12 months after treatment were observed and analyzed.Results A total of 100 patients with CML-CP were enrolled,with a median follow-up of 18(3~36)months.The optimal response rate was 92.6%(88/95),94.4%(85/90)and 92.9%(79/85)respectively,at 3,6 and 12 months after treatment.Till August 20,2023,the cumulative CCyR and MMR rate was 98.0%(98/100)and 81.9%(77/94),respectively,the median time to reach CCyR and MMR was 3 months,and cumulative DMR rate was 51.0%(51/100).PFS rate was 100.0%(100/100)and 1-year EFS rate was 85.6%(75/90).The most common non-hematologic adverse reactions of flumatinib were diarrhea and abdominal pain(7.0%),followed by renal dysfunction(6.0%)and musculoskeletal pain(2.0%).The main hematologic adverse reactions were thrombocytopenia(12.0%),anemia(6.0%)and leukopenia(2.0%).Conclusion Flumatinib has better MMR and DMR and is well tolerated in CML-CP patients with TKI resistance or intolerance.

关 键 词：慢性髓系白血病 BCR-ABL阳性 TKI 氟马替尼 

分 类 号：R181.32[医药卫生—流行病学] R733.7[医药卫生—公共卫生与预防医学] R979.12