摘要
目的探讨酪氨酸激酶抑制剂(TKI)减量方案治疗慢性粒细胞白血病(CML)慢性期患者的效果及其对预后的影响。方法回顾性队列研究。收集2018年1月至2022年12月苏州大学附属第一医院接受TKI减量方案治疗的CML慢性期患者临床资料。依据Sokal评分、欧洲治疗和结果研究长期生存(ELTS)评分、TKI药物类别及其减量幅度、治疗阶段进行分组。比较不同分层患者总生存(OS)、主要分子学反应(MMR)累积发生率、累积分子学复发率和无事件生存(EFS)。采用Kaplan-Meier法进行生存分析。结果154例CML慢性期患者,接受减量TKI药物治疗中位时间[M(IQR)]35.4个月(34.9个月);Sokal评分高危、中低危组分别为20例(12.99%)、134例(87.01%),ELTS评分高危、中低危组分别为14例(9.09%)、140例(90.91%)。83例(53.90%)接受伊马替尼治疗,71例(46.10%)接受二代TKI治疗;138例(89.61%)TKI药物剂量稳定在第一阶梯剂量,16例(10.39%)稳定在第二阶梯剂量。诱导治疗组33例(21.43%),维持治疗组121例(78.57%)。154例患者3年OS率为90.6%。Sokal评分高危组患者3年OS率低于中低危组患者(64.1%比96.7%)(P<0.001);ELTS评分高危组患者3年OS率低于中低危组患者(62.9%比95.8%)(P=0.002)。接受第一阶梯剂量治疗的患者3年OS率为90.6%,与接受第二阶梯剂量治疗患者的3年OS率(90.0%)比较差异无统计学意义(P=0.478);诱导治疗组3年OS率为88.9%,与维持治疗组3年OS率(91.4%)相比,差异无统计学意义(P=0.868)。33例诱导治疗组患者治疗剂量均为第一阶梯剂量;治疗后28例达MMR,2例达分子学反应4.0(MR4.0);所有诱导治疗组患者1年MMR累积发生率为95.8%,中位达MMR时间8.4个月;Sokal评分高危组患者1年MMR累积发生率为50.0%,低于中低危组患者(95.3%)(P=0.014),达MMR的中位时间分别为14.7个月和7.8个月;使用一代TKI药物治疗的患者1年MMR累积发生率低于使用二代TKI药物的患者(65.0%比100.0%,P=0.034),且达MMR的中位时间更长,分别为9.1个月和6.9个月。149例患者获得MMR,其中5例出现分子学复发,3年累积分子学复发率为8.3%。Sokal评分中低危组3年累积分子学复发率(1.5%比39.8%,P<0.001)、EFS率(92.3%比57.1%,P<0.001)和OS率(100.0%比62.8%,P<0.001)均优于Sokal评分高危组;接受第一阶梯剂量治疗患者3年累积分子学复发率、3年EFS率优于接受第二阶梯剂量治疗患者,差异均有统计学意义(均P<0.001)。结论CML慢性期患者接受减量的TKI药物治疗仍可获得较好疗效,但高危组患者预后相对较差。TKI药物和减量幅度宜根据患者具体情况进行个体化选择。
Objective To explore the effect of tyrosine kinase inhibitor(TKI)dose reduction regimen in patients with chronic-phase chronic myeloid leukemia(CML)and its prognostic impact.Methods A retrospective cohort study was conducted.The clinical data of patients with chronic-phase CML treated with reduced-dose TKI in the First Affiliated Hospital of Soochow University between January 2018 and December 2022 were collected.Patients were divided into groups based on Sokal score,European Treatment and Outcome Study long-term survival(ELTS)score,TKI drug classification and dose reduction,and treatment phase.The overall survival(OS),the cumulative incidence of major molecular response(MMR),the cumulative molecular recurrence rate and event-free survival(EFS)among patients in different strata were compared.Kaplan-Meier method was used for survival analysis.Results Among 154 patients with chronic-phase CML,the median duration[M(IQR)]of reduced-dose TKI therapy was 35.4 months(34.9 months);Sokal score high-risk and low-/intermediate-risk groups comprised 20 cases(12.99%)and 134 cases(87.01%),respectively;ELTS score high-risk and low-/intermediate-risk groups comprised 14 cases(9.09%)and 140 cases(90.91%),respectively.Among 154 patients,83 cases(53.90%)received imatinib therapy,while 71 cases(46.10%)received second-generation TKI;138 patients(89.61%)maintained stable TKI dosing at the first dose level,and 16 patients(10.39%)maintained it at the second dose level.The induction therapy group comprised 33 patients(21.43%),while the maintenance therapy group included 121 patients(78.57%).The 3-year OS rate of all 154 patients was 90.6%.Patients in the Sokal score high-risk group demonstrated a lower 3-year OS rate compared to those in the low-/intermediate-risk group(64.1%vs.96.7%)(P<0.001);patients in the ELTS score high-risk group had a lower 3-year OS rate compared to those in the low-/intermediate-risk group(62.9%vs.95.8%)(P=0.002).There was no statistically significant difference in the 3-year OS rate of patients receiving the first dose level and those receiving the second dose level(90.6%vs.90.0%,P=0.478);there was no statistically significant difference in the 3-year OS rate of the induction therapy group and the maintenance therapy group(88.9%vs.91.4%,P=0.868).Among the 33 patients in the induction therapy group,all received the first dose level.After treatment,28 achieved MMR,and 2 achieved molecular response 4.0(MR4.0).The cumulative 1-year MMR rate of all patients in reduction therapy group was 95.8%,with a median time to MMR of 8.4 months;patients in the high-risk Sokal score group had a 1-year cumulative MMR rate of 50.0%,which was lower than that of the low-/intermediate-risk group(95.3%)(P=0.014);the median time to MMR was 14.7 months and 7.8 months,respectively.The cumulative 1-year MMR rate of patients treated with first-generation TKI was lower than that in those treated with second-generation TKI(65.0%vs.100.0%,P=0.034),and the median time to MMR of patients treated with first-generation TKI was longer than that those treated with second-generation TKI(9.1 months vs.6.9 months).Among the 149 patients who achieved MMR,5 experienced molecular relapse,resulting in a 3-year cumulative molecular relapse rate of 8.3%.In the Sokal score low-/intermediate-risk group,the 3-year cumulative molecular relapse rate(1.5%vs.39.8%,P<0.001),EFS rate(92.3%vs.57.1%,P<0.001),and OS rate(100.0%vs.62.8%,P<0.001)were better than those in the Sokal score high-risk group.The 3-year cumulative molecular relapse rate and 3-year EFS rate in patients receiving first dose level therapy were better than those in patients receiving second dose level therapy,and the differences were statistically significant(all P<0.001).Conclusions Patients with chronic-phase CML can still obtain good outcomes when receiving dose-reduced TKI,while the prognosis of patients in high-risk group is relatively poor.The choice of TKI and the dosage reduction should be individualized based on patients'characteristics.
作者
沈娟
朱锦锦
徐蜜蜜
屠雨青
陈楠
许姝姝
程佳
Shen Juan;Zhu Jinjin;Xu Mimi;Tu Yuqing;Chen Nan;Xu Shushu;Cheng Jia(Department of Hematology,the First Affiliated Hospital of Soochow University,National Clinical Research Center for Hematologic Diseases,Jiangsu Institute of Hematology,Suzhou 215006,China)
出处
《白血病.淋巴瘤》
2025年第10期586-591,共6页
Journal of Leukemia & Lymphoma
基金
江苏省血液病医学创新中心(CXZX202201)。
